News

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

A version of this article first appeared on Medscape.com.

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

A version of this article first appeared on Medscape.com.

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

A version of this article first appeared on Medscape.com.

TOPLINE:

The analysis of 11,427 US Deparment of Veterans Affairs (VA) hospital patients with multiple myeloma (MM) reveals that lymphopenia affects 53% of patients at diagnosis. The median overall survival was 2.7 years in patients with severely low absolute lymphocyte count vs 4.2 years in those with normal counts.

METHODOLOGY:

• Researchers evaluated 11,427 patients diagnosed with MM between 2000 and 2019 at VA medical centers using absolute lymphocyte count obtained closest to diagnosis and up to 2.5 years thereafter.
• Patients were stratified into three absolute lymphocyte count categories: Severely low (less than 1 × 10⁹/μL), low (1 × 10⁹/μL to 1.5 × 10⁹/μL), and normal (> 1.5 × 10⁹/μL).
• Analysis excluded patients with acute and chronic leukemias, aplastic anemia, myelodysplastic syndrome, hairy cell leukemia, or myeloproliferative neoplasms before MM diagnosis.
• Follow-up duration extended from diagnosis until development of another hematologic malignancy, death, truncation date (15 years after diagnosis), or study end date.

TAKEAWAY:

• Lymphopenia was present in 53% of patients at MM diagnosis and was associated with inferior overall survival.
• Median overall survival for patients with severely low, low, and normal absolute lymphocyte count at diagnosis was 2.7 years, 3.3 years, and 4.2 years, respectively (P < .001).
• Persistent or new development of lymphopenia during treatment and follow-up was linked to inferior overall survival.
• Standard induction therapy with lenalidomide, bortezomib, and dexamethasone did not overcome inferior outcomes in patients with lymphopenia, showing median overall survival of 3.6 years, 4.6 years, and 5.7 years among patients with severely low, low, and normal baseline absolute lymphocyte count, respectively (P less than .001).

IN PRACTICE:

“Because immune dysregulation and immunosenescence in the bone marrow microenvironment are reflected in the peripheral blood lymphocyte count and peripheral blood markers may, in turn, correlate with clinical features and outcome in MM, we sought to identify clinical features correlating with peripheral blood lymphopenia and evaluate absolute lymphocyte count at diagnosis as a predictor of outcome in MM and in the context of standard induction treatment,” the authors wrote.

SOURCE:

This study was led by Grace M. Ferri and Cenk Yildirim, Boston Medical Center in Boston. It was published online in Blood Advances.

LIMITATIONS:

This study population consisted predominantly of male participants due to being conducted in the VA system. Additionally, researchers acknowledged that lymphopenia could not be exclusively attributed to MM, as other treatments common in older populations might contribute. The use of alkylating agents like cyclophosphamide and melphalan during treatment could also influence lymphopenia levels.

DISCLOSURES:

Individual-level data underlying this study are available to researchers with VA regulatory approval, consistent with VA policy.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

The analysis of 11,427 US Deparment of Veterans Affairs (VA) hospital patients with multiple myeloma (MM) reveals that lymphopenia affects 53% of patients at diagnosis. The median overall survival was 2.7 years in patients with severely low absolute lymphocyte count vs 4.2 years in those with normal counts.

METHODOLOGY:

• Researchers evaluated 11,427 patients diagnosed with MM between 2000 and 2019 at VA medical centers using absolute lymphocyte count obtained closest to diagnosis and up to 2.5 years thereafter.
• Patients were stratified into three absolute lymphocyte count categories: Severely low (less than 1 × 10⁹/μL), low (1 × 10⁹/μL to 1.5 × 10⁹/μL), and normal (> 1.5 × 10⁹/μL).
• Analysis excluded patients with acute and chronic leukemias, aplastic anemia, myelodysplastic syndrome, hairy cell leukemia, or myeloproliferative neoplasms before MM diagnosis.
• Follow-up duration extended from diagnosis until development of another hematologic malignancy, death, truncation date (15 years after diagnosis), or study end date.

TAKEAWAY:

• Lymphopenia was present in 53% of patients at MM diagnosis and was associated with inferior overall survival.
• Median overall survival for patients with severely low, low, and normal absolute lymphocyte count at diagnosis was 2.7 years, 3.3 years, and 4.2 years, respectively (P < .001).
• Persistent or new development of lymphopenia during treatment and follow-up was linked to inferior overall survival.
• Standard induction therapy with lenalidomide, bortezomib, and dexamethasone did not overcome inferior outcomes in patients with lymphopenia, showing median overall survival of 3.6 years, 4.6 years, and 5.7 years among patients with severely low, low, and normal baseline absolute lymphocyte count, respectively (P less than .001).

IN PRACTICE:

“Because immune dysregulation and immunosenescence in the bone marrow microenvironment are reflected in the peripheral blood lymphocyte count and peripheral blood markers may, in turn, correlate with clinical features and outcome in MM, we sought to identify clinical features correlating with peripheral blood lymphopenia and evaluate absolute lymphocyte count at diagnosis as a predictor of outcome in MM and in the context of standard induction treatment,” the authors wrote.

SOURCE:

This study was led by Grace M. Ferri and Cenk Yildirim, Boston Medical Center in Boston. It was published online in Blood Advances.

LIMITATIONS:

This study population consisted predominantly of male participants due to being conducted in the VA system. Additionally, researchers acknowledged that lymphopenia could not be exclusively attributed to MM, as other treatments common in older populations might contribute. The use of alkylating agents like cyclophosphamide and melphalan during treatment could also influence lymphopenia levels.

DISCLOSURES:

Individual-level data underlying this study are available to researchers with VA regulatory approval, consistent with VA policy.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

The analysis of 11,427 US Deparment of Veterans Affairs (VA) hospital patients with multiple myeloma (MM) reveals that lymphopenia affects 53% of patients at diagnosis. The median overall survival was 2.7 years in patients with severely low absolute lymphocyte count vs 4.2 years in those with normal counts.

METHODOLOGY:

• Researchers evaluated 11,427 patients diagnosed with MM between 2000 and 2019 at VA medical centers using absolute lymphocyte count obtained closest to diagnosis and up to 2.5 years thereafter.
• Patients were stratified into three absolute lymphocyte count categories: Severely low (less than 1 × 10⁹/μL), low (1 × 10⁹/μL to 1.5 × 10⁹/μL), and normal (> 1.5 × 10⁹/μL).
• Analysis excluded patients with acute and chronic leukemias, aplastic anemia, myelodysplastic syndrome, hairy cell leukemia, or myeloproliferative neoplasms before MM diagnosis.
• Follow-up duration extended from diagnosis until development of another hematologic malignancy, death, truncation date (15 years after diagnosis), or study end date.

TAKEAWAY:

• Lymphopenia was present in 53% of patients at MM diagnosis and was associated with inferior overall survival.
• Median overall survival for patients with severely low, low, and normal absolute lymphocyte count at diagnosis was 2.7 years, 3.3 years, and 4.2 years, respectively (P < .001).
• Persistent or new development of lymphopenia during treatment and follow-up was linked to inferior overall survival.
• Standard induction therapy with lenalidomide, bortezomib, and dexamethasone did not overcome inferior outcomes in patients with lymphopenia, showing median overall survival of 3.6 years, 4.6 years, and 5.7 years among patients with severely low, low, and normal baseline absolute lymphocyte count, respectively (P less than .001).

IN PRACTICE:

“Because immune dysregulation and immunosenescence in the bone marrow microenvironment are reflected in the peripheral blood lymphocyte count and peripheral blood markers may, in turn, correlate with clinical features and outcome in MM, we sought to identify clinical features correlating with peripheral blood lymphopenia and evaluate absolute lymphocyte count at diagnosis as a predictor of outcome in MM and in the context of standard induction treatment,” the authors wrote.

SOURCE:

This study was led by Grace M. Ferri and Cenk Yildirim, Boston Medical Center in Boston. It was published online in Blood Advances.

LIMITATIONS:

This study population consisted predominantly of male participants due to being conducted in the VA system. Additionally, researchers acknowledged that lymphopenia could not be exclusively attributed to MM, as other treatments common in older populations might contribute. The use of alkylating agents like cyclophosphamide and melphalan during treatment could also influence lymphopenia levels.

DISCLOSURES:

Individual-level data underlying this study are available to researchers with VA regulatory approval, consistent with VA policy.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

•       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
•       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
•       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

•      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
•      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
•      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

•       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
•       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
•       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

•      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
•      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
•      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

•       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
•       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
•       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

•      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
•      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
•      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for the treatment of certain adult patients with metastatic colorectal cancer (mCRC).

Specifically, the combination therapy is indicated for those with KRAS G12C-mutated mCRC, as determined using an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, according to the FDA notice. The FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device for identifying eligible patients.

Approval of sotorasib with panitumumab was based on findings from the randomized, open-label, controlled CodeBreaK 300 trial showing improved overall response rates (ORR) and progression-free survival (PFS) with sotorasib and panitumumab vs investigator’s choice of trifluridine/tipiracil or regorafenib, which are current standard-of-care options.

Median PFS was 5.6 months in 53 patients randomized to receive 960 mg of oral sotorasib once daily plus 6 mg/kg of intravenous (IV) panitumumab every 2 weeks, and 2 months in 54 patients randomized to receive standard-of-care therapy (hazard ratio, 0.48). The ORR was 26% vs 0% in the arms, respectively, and the duration of response in the sotorasib/panitumumab arm was 4.4 months. No significant difference in PFS was observed between the standard-of-care arm and a third arm with 53 patients who received 240 mg of oral sotorasib daily plus 6 mg/kg of IV panitumumab every 2 weeks.

Overall survival (OS) did not differ significantly between the treatment arms in the final analysis, but the study was not statistically powered for OS.

Adverse reactions occurring in at least 20% of patients receiving sotorasib/panitumumab were rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. Common grade 3-4 laboratory abnormalities, which occurred in two or more patients, included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.

The recommended dose of sotorasib is 960 mg given orally once daily and administered before the first panitumumab infusion. The recommended panitumumab dose is 6 mg/kg as an IV infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued, according to the full prescribing information.

A version of this article first appeared on Medscape.com.

TOPLINE:

Physical activity before stage I cancer diagnosis is associated with reduced risk for disease progression and mortality. Members engaging in at least 60 minutes of weekly physical activity showed a 27% lower risk for progression and 47% lower risk for mortality compared with inactive individuals.

METHODOLOGY:

• Physical activity plays a significant role in reducing cancer mortality with high levels having been associated with an 18% reduction in cancer-specific mortality compared with lower levels in patients with pre- and/or post-diagnosed cancer.
• The new analysis included 28,248 members with stage I cancers enrolled in an oncology programme in South Africa, with physical activity recorded through fitness devices, logged gym sessions, and participation in organized events.
• Participants were categorized into three groups: No physical activity (0 min/wk), low physical activity (< 60 min/wk), and moderate to high physical activity (≥ 60 min/wk) based on activity levels 12 months before diagnosis.
• Researchers measured outcomes including time to progression, time to death, and all-cause mortality, with a follow-up period ranging from 1-154 months.
• Analysis adjusted for covariates including age, sex, socioeconomic status, and patient complexity measured by Johns Hopkins Adjusted Clinical Groups Systems software.

TAKEAWAY:

• Members with low physical activity showed a hazard ratio (HR) of 0.84 (95% CI, 0.79-0.89) for progression or death compared with those with no activity, whereas those with moderate to high activity showed an HR of 0.73 (95% CI, 0.70-0.77).
• For all-cause mortality, low physical activity members demonstrated an HR of 0.67 (95% CI, 0.61-0.74), whereas moderate to high activity members showed an HR of 0.53 (95% CI, 0.50-0.58) compared with inactive members.
• At 24 months post-diagnosis, individuals with moderate to high physical activity showed 80% probability of nonprogression compared with 74% for inactive individuals.
• Survival probability at 24 months was 95% for moderate to high activity members vs 91% for those with no physical activity.

IN PRACTICE:

“Physical activity may be considered to confer substantial benefits in terms of progression and overall mortality to those diagnosed with cancer. In a world where cancer continues to be a significant public health burden, the promotion of physical activity can yield important benefits regarding the progression of cancer as well as its prevention and management,” the authors of the study wrote.

SOURCE:

This study was led by Ntokozo Mabena of Discovery Vitality in Sandton, South Africa. It was published online in British Journal of Sports Medicine.

LIMITATIONS:

According to the authors, potential biases exist from not adjusting for confounding factors such as smoking status and alcohol consumption, along with incomplete body mass index data. The study assumed members without recorded physical activity points were inactive, which may not be accurate for all individuals. The findings may not be generalizable to the broader South African population as the study cohort had access to private medical insurance.

DISCLOSURES:

Authors Mabena, Sandra Lehmann, Deepak Patel, and Mosima Mabunda are employed by Discovery. Other authors Mike Greyling and Jon S. Patricios serve as a consultant for Discovery and an editor of British Journal of Sports Medicine, respectively.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Physical activity before stage I cancer diagnosis is associated with reduced risk for disease progression and mortality. Members engaging in at least 60 minutes of weekly physical activity showed a 27% lower risk for progression and 47% lower risk for mortality compared with inactive individuals.

METHODOLOGY:

• Physical activity plays a significant role in reducing cancer mortality with high levels having been associated with an 18% reduction in cancer-specific mortality compared with lower levels in patients with pre- and/or post-diagnosed cancer.
• The new analysis included 28,248 members with stage I cancers enrolled in an oncology programme in South Africa, with physical activity recorded through fitness devices, logged gym sessions, and participation in organized events.
• Participants were categorized into three groups: No physical activity (0 min/wk), low physical activity (< 60 min/wk), and moderate to high physical activity (≥ 60 min/wk) based on activity levels 12 months before diagnosis.
• Researchers measured outcomes including time to progression, time to death, and all-cause mortality, with a follow-up period ranging from 1-154 months.
• Analysis adjusted for covariates including age, sex, socioeconomic status, and patient complexity measured by Johns Hopkins Adjusted Clinical Groups Systems software.

TAKEAWAY:

• Members with low physical activity showed a hazard ratio (HR) of 0.84 (95% CI, 0.79-0.89) for progression or death compared with those with no activity, whereas those with moderate to high activity showed an HR of 0.73 (95% CI, 0.70-0.77).
• For all-cause mortality, low physical activity members demonstrated an HR of 0.67 (95% CI, 0.61-0.74), whereas moderate to high activity members showed an HR of 0.53 (95% CI, 0.50-0.58) compared with inactive members.
• At 24 months post-diagnosis, individuals with moderate to high physical activity showed 80% probability of nonprogression compared with 74% for inactive individuals.
• Survival probability at 24 months was 95% for moderate to high activity members vs 91% for those with no physical activity.

IN PRACTICE:

“Physical activity may be considered to confer substantial benefits in terms of progression and overall mortality to those diagnosed with cancer. In a world where cancer continues to be a significant public health burden, the promotion of physical activity can yield important benefits regarding the progression of cancer as well as its prevention and management,” the authors of the study wrote.

SOURCE:

This study was led by Ntokozo Mabena of Discovery Vitality in Sandton, South Africa. It was published online in British Journal of Sports Medicine.

LIMITATIONS:

According to the authors, potential biases exist from not adjusting for confounding factors such as smoking status and alcohol consumption, along with incomplete body mass index data. The study assumed members without recorded physical activity points were inactive, which may not be accurate for all individuals. The findings may not be generalizable to the broader South African population as the study cohort had access to private medical insurance.

DISCLOSURES:

Authors Mabena, Sandra Lehmann, Deepak Patel, and Mosima Mabunda are employed by Discovery. Other authors Mike Greyling and Jon S. Patricios serve as a consultant for Discovery and an editor of British Journal of Sports Medicine, respectively.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

TOPLINE:

Physical activity before stage I cancer diagnosis is associated with reduced risk for disease progression and mortality. Members engaging in at least 60 minutes of weekly physical activity showed a 27% lower risk for progression and 47% lower risk for mortality compared with inactive individuals.

METHODOLOGY:

• Physical activity plays a significant role in reducing cancer mortality with high levels having been associated with an 18% reduction in cancer-specific mortality compared with lower levels in patients with pre- and/or post-diagnosed cancer.
• The new analysis included 28,248 members with stage I cancers enrolled in an oncology programme in South Africa, with physical activity recorded through fitness devices, logged gym sessions, and participation in organized events.
• Participants were categorized into three groups: No physical activity (0 min/wk), low physical activity (< 60 min/wk), and moderate to high physical activity (≥ 60 min/wk) based on activity levels 12 months before diagnosis.
• Researchers measured outcomes including time to progression, time to death, and all-cause mortality, with a follow-up period ranging from 1-154 months.
• Analysis adjusted for covariates including age, sex, socioeconomic status, and patient complexity measured by Johns Hopkins Adjusted Clinical Groups Systems software.

TAKEAWAY:

• Members with low physical activity showed a hazard ratio (HR) of 0.84 (95% CI, 0.79-0.89) for progression or death compared with those with no activity, whereas those with moderate to high activity showed an HR of 0.73 (95% CI, 0.70-0.77).
• For all-cause mortality, low physical activity members demonstrated an HR of 0.67 (95% CI, 0.61-0.74), whereas moderate to high activity members showed an HR of 0.53 (95% CI, 0.50-0.58) compared with inactive members.
• At 24 months post-diagnosis, individuals with moderate to high physical activity showed 80% probability of nonprogression compared with 74% for inactive individuals.
• Survival probability at 24 months was 95% for moderate to high activity members vs 91% for those with no physical activity.

IN PRACTICE:

“Physical activity may be considered to confer substantial benefits in terms of progression and overall mortality to those diagnosed with cancer. In a world where cancer continues to be a significant public health burden, the promotion of physical activity can yield important benefits regarding the progression of cancer as well as its prevention and management,” the authors of the study wrote.

SOURCE:

This study was led by Ntokozo Mabena of Discovery Vitality in Sandton, South Africa. It was published online in British Journal of Sports Medicine.

LIMITATIONS:

According to the authors, potential biases exist from not adjusting for confounding factors such as smoking status and alcohol consumption, along with incomplete body mass index data. The study assumed members without recorded physical activity points were inactive, which may not be accurate for all individuals. The findings may not be generalizable to the broader South African population as the study cohort had access to private medical insurance.

DISCLOSURES:

Authors Mabena, Sandra Lehmann, Deepak Patel, and Mosima Mabunda are employed by Discovery. Other authors Mike Greyling and Jon S. Patricios serve as a consultant for Discovery and an editor of British Journal of Sports Medicine, respectively.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Hello. I’m Dr. Maurie Markman from City of Hope. I wanted to briefly discuss a very important paper. This is one that probably didn’t get as much attention as I believe it should. It looks at a very important clinically relevant question, and one that might very much say, can we do more such studies but only do them faster?

This was a trial reported in the Journal of Clinical Oncology earlier this year titled, “Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Study.” 

Fortunately, most patients with endometrial cancer have low-grade cancers and are cured with standard surgery, plus or minus radiation. However, a small percentage of patients, even with low-grade endometrial cancer, will recur.

There are several questions that come up. What is the optimal therapy? What is the outcome for such patients? Should we perhaps give chemotherapy along with the radiation as we do, for example, standardly in cervical cancer?

This study attempted to address that question. There was a total of 165 patients randomized in this trial that went on for 12 years, looking at local radiation vs radiation plus cisplatin — which is, again, standardly given as chemoradiation in cervical cancer.

What were the results? When this paper was reported 16 years after the study was initiated, the results showed the addition of chemotherapy did not add to the benefits of the radiation and in fact increased toxicity. Very importantly, the local control and overall control of the disease was excellent. In fact, at 3 years, 73% of the patients treated with radiation alone were disease-free.

It’s very important to know this, the value of radiation, and that adding chemotherapy with radiation doesn’t make a difference.

One might ask, if this is an important clinical question, is there a way or would there be a way in the future to take a question like this and significantly expand the population of individuals and the population of oncologists that might participate in community-based studies, where you’re asking a very simple question? 

You irradiate vs something else; you have a standard of care; you’re looking at progression-free survival, which is a very valid endpoint, or overall survival, and you don’t anticipate significant differences in toxicity because you might use this therapy otherwise. 

Would it be possible to answer the question not in 12 years, but in half that time or maybe 20% of that time? The results are important for patients being treated today and their doctors who are advising on optimal therapy.

For those of you who are interested in the question of the management of endometrial cancer, this type of pragmatic trial, I would encourage you to read this important paper. Thank you for your attention.

Maurie Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from GlaxoSmithKline and AstraZeneca.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Hello. I’m Dr. Maurie Markman from City of Hope. I wanted to briefly discuss a very important paper. This is one that probably didn’t get as much attention as I believe it should. It looks at a very important clinically relevant question, and one that might very much say, can we do more such studies but only do them faster?

This was a trial reported in the Journal of Clinical Oncology earlier this year titled, “Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Study.” 

Fortunately, most patients with endometrial cancer have low-grade cancers and are cured with standard surgery, plus or minus radiation. However, a small percentage of patients, even with low-grade endometrial cancer, will recur.

There are several questions that come up. What is the optimal therapy? What is the outcome for such patients? Should we perhaps give chemotherapy along with the radiation as we do, for example, standardly in cervical cancer?

This study attempted to address that question. There was a total of 165 patients randomized in this trial that went on for 12 years, looking at local radiation vs radiation plus cisplatin — which is, again, standardly given as chemoradiation in cervical cancer.

What were the results? When this paper was reported 16 years after the study was initiated, the results showed the addition of chemotherapy did not add to the benefits of the radiation and in fact increased toxicity. Very importantly, the local control and overall control of the disease was excellent. In fact, at 3 years, 73% of the patients treated with radiation alone were disease-free.

It’s very important to know this, the value of radiation, and that adding chemotherapy with radiation doesn’t make a difference.

One might ask, if this is an important clinical question, is there a way or would there be a way in the future to take a question like this and significantly expand the population of individuals and the population of oncologists that might participate in community-based studies, where you’re asking a very simple question? 

You irradiate vs something else; you have a standard of care; you’re looking at progression-free survival, which is a very valid endpoint, or overall survival, and you don’t anticipate significant differences in toxicity because you might use this therapy otherwise. 

Would it be possible to answer the question not in 12 years, but in half that time or maybe 20% of that time? The results are important for patients being treated today and their doctors who are advising on optimal therapy.

For those of you who are interested in the question of the management of endometrial cancer, this type of pragmatic trial, I would encourage you to read this important paper. Thank you for your attention.

Maurie Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from GlaxoSmithKline and AstraZeneca.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Hello. I’m Dr. Maurie Markman from City of Hope. I wanted to briefly discuss a very important paper. This is one that probably didn’t get as much attention as I believe it should. It looks at a very important clinically relevant question, and one that might very much say, can we do more such studies but only do them faster?

This was a trial reported in the Journal of Clinical Oncology earlier this year titled, “Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Study.” 

Fortunately, most patients with endometrial cancer have low-grade cancers and are cured with standard surgery, plus or minus radiation. However, a small percentage of patients, even with low-grade endometrial cancer, will recur.

There are several questions that come up. What is the optimal therapy? What is the outcome for such patients? Should we perhaps give chemotherapy along with the radiation as we do, for example, standardly in cervical cancer?

This study attempted to address that question. There was a total of 165 patients randomized in this trial that went on for 12 years, looking at local radiation vs radiation plus cisplatin — which is, again, standardly given as chemoradiation in cervical cancer.

What were the results? When this paper was reported 16 years after the study was initiated, the results showed the addition of chemotherapy did not add to the benefits of the radiation and in fact increased toxicity. Very importantly, the local control and overall control of the disease was excellent. In fact, at 3 years, 73% of the patients treated with radiation alone were disease-free.

It’s very important to know this, the value of radiation, and that adding chemotherapy with radiation doesn’t make a difference.

One might ask, if this is an important clinical question, is there a way or would there be a way in the future to take a question like this and significantly expand the population of individuals and the population of oncologists that might participate in community-based studies, where you’re asking a very simple question? 

You irradiate vs something else; you have a standard of care; you’re looking at progression-free survival, which is a very valid endpoint, or overall survival, and you don’t anticipate significant differences in toxicity because you might use this therapy otherwise. 

Would it be possible to answer the question not in 12 years, but in half that time or maybe 20% of that time? The results are important for patients being treated today and their doctors who are advising on optimal therapy.

For those of you who are interested in the question of the management of endometrial cancer, this type of pragmatic trial, I would encourage you to read this important paper. Thank you for your attention.

Maurie Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from GlaxoSmithKline and AstraZeneca.

A version of this article first appeared on Medscape.com.

A young boy with a habit of screaming when he didn’t get his way is among the patients Joannie Yeh, MD, a primary care physician at Nemours Children’s Health in Media, Pennsylvania, has helped in her practice.

Yeh taught the boy to stretch out his hands into the shape of a starfish, then trace around the edges of his fingers while breathing slowly and deeply. His parents later reported that after using the strategy at home, their son was no longer taking his rage out on his younger siblings.

Interventions like breathing exercises are just a few techniques Yeh hopes more primary care clinicians will teach young patients as mental health issues among this population soar to a national state of emergency, major medical groups say. But many children go without treatment because of shortages of mental health clinicians and long wait-lists for appointments.

“Knowledge of different types of interventions allows pediatricians to offer more options to families — more than just medication alone,” Yeh said. “There are some strategies, like cognitive behavioral therapy, that a therapist is equipped to deliver, but we can help explain them or teach simple skills that borrow from principles of higher-level techniques and can help patients and families while they wait to see a therapist.”

The use of techniques that are based on mindfulness, cognitive behavioral therapy, and psychotherapy are especially helpful to pediatricians after a child’s answers on a screener indicate they may be struggling with anxiety, depression, or attention-deficit/hyperactivity disorder (ADHD), said Theresa Nguyen, MD, chair of pediatrics at Greater Baltimore Medical Center, Baltimore.

“It kind of sucks if you come in worried and then your doctor says, ‘Okay, let me send you to a psychiatrist who you can’t see for 6 months; let me send you to a therapist who’s going to take a couple of weeks to get in with,’” Nguyen said.

Yeh said over the past few years she has cared for more youth coming in as follow-ups after an emergency department visit for a mental health episode.

“Oftentimes, this is the first time we become aware that the child is struggling,” Yeh said. “We are seeing issues like intentional medication overdose, referrals after other self-harm actions, or even the discovery of a note indicating the intention to do harm to self.”

Suicide deaths among 10- to 14-year-olds tripled between 2007 and 2018 and held steady through 2021, with rates climbing even among children as young as 8 years, according to a research in JAMA Network Open. Meanwhile, one in five high school students seriously contemplated suicide in 2023 (27% girls, 14% boys).

 

Mental Health Strategies for Kids in Primary Care

While pediatricians cannot replace a mental health professional, they have the unique advantage of maintaining a long-term relationship with patients. Experts said clinicians should take an active role in supporting the mental health of patients through a variety of evidence-based strategies.

Changing Thought Patterns 

Cognitive-behavioral therapy (CBT) involves identifying and challenging automatic negative thoughts, which can affect a child’s emotional state and lead to behaviors like withdrawal or lashing out.

Yeh recommended asking a child about what is bothering them, pointing out unhelpful and negative thoughts, and then offering a different, positive one instead.

She also often draws a picture of the CBT chart, which is a visual representation of how feelings lead to thoughts, and then behaviors.

“I draw this diagram because it helps give the patients a visual understanding of how their feelings and emotions are connected,” Yeh said.

 

Tools to Tolerate Stressful Situations

Simple tools like breathing exercises, body scanning, and physical exercise can help children better tolerate distress.

Pediatricians can also recommend families use guided meditations, which have been shown to lower anxiety and increase positive social behavior, said Mollie Grow, MD, an associate professor of pediatrics at the University of Washington Medicine and Seattle Children’s Hospital, both in Seattle.

But a child might first need to get negative energy out before they can become calm.

“So I’m like, ‘okay, let’s do actual physical exercise. Give me 10 jumping jacks.’ No one’s nervous after those jumping jacks,” Nguyen said. “When you’ve already been triggered, your nerves have gotten going, and you’re starting to spiral, you can’t slow yourself down enough to do a breathing exercise.”

Nguyen also said that cold water quickly calms the nervous system.

“I’ll run cold water in the office and have them put their hand in it until it’s almost frozen,” and the child or teen is able to think more clearly, Nguyen said. “It’s a real physiological response. It works.”

 

The Origin of a Feeling 

Explaining how symptoms of anxiety, depression, or ADHD work can help children and teens better understand that what they are experiencing is normal and better cope, Yeh said.

Clinicians might teach patients about how shallow breathing — a symptom of anxiety — is a result of the brain scanning for danger, and how slowing breathing tricks the brain into feeling safe again.

 

Barriers Abound

The use of these interventions in pediatric settings is not yet widespread, Grow said.

But starting in July 2025, the Accreditation Council for Graduate Medical Education will require pediatric residencies to include 4 weeks of mental health training. How that requirement is fulfilled will be up to residencies, said Brian Alverson, MD, pediatric program director and vice-chair of education at Nemours Children’s Hospital in Wilmington, Delaware.

Even with training, many pediatricians lack the time to address mental health issues during an office visit, said Carlos Lerner, MD, a professor of clinical pediatrics at University of California, Los Angeles Health. And despite low or sometimes no reimbursement for discussing these issues with patients, “the reality is we end up doing it anyway.”

Treating issues like anxiety and depression “is a daily, constant part of the care that I provide for my patients,” said Lerner. “Whether the pandemic or social media exacerbated it, we are absolutely seeing a rise in mental health issues.”

A version of this article first appeared on Medscape.com.

A young boy with a habit of screaming when he didn’t get his way is among the patients Joannie Yeh, MD, a primary care physician at Nemours Children’s Health in Media, Pennsylvania, has helped in her practice.

Yeh taught the boy to stretch out his hands into the shape of a starfish, then trace around the edges of his fingers while breathing slowly and deeply. His parents later reported that after using the strategy at home, their son was no longer taking his rage out on his younger siblings.

Interventions like breathing exercises are just a few techniques Yeh hopes more primary care clinicians will teach young patients as mental health issues among this population soar to a national state of emergency, major medical groups say. But many children go without treatment because of shortages of mental health clinicians and long wait-lists for appointments.

“Knowledge of different types of interventions allows pediatricians to offer more options to families — more than just medication alone,” Yeh said. “There are some strategies, like cognitive behavioral therapy, that a therapist is equipped to deliver, but we can help explain them or teach simple skills that borrow from principles of higher-level techniques and can help patients and families while they wait to see a therapist.”

The use of techniques that are based on mindfulness, cognitive behavioral therapy, and psychotherapy are especially helpful to pediatricians after a child’s answers on a screener indicate they may be struggling with anxiety, depression, or attention-deficit/hyperactivity disorder (ADHD), said Theresa Nguyen, MD, chair of pediatrics at Greater Baltimore Medical Center, Baltimore.

“It kind of sucks if you come in worried and then your doctor says, ‘Okay, let me send you to a psychiatrist who you can’t see for 6 months; let me send you to a therapist who’s going to take a couple of weeks to get in with,’” Nguyen said.

Yeh said over the past few years she has cared for more youth coming in as follow-ups after an emergency department visit for a mental health episode.

“Oftentimes, this is the first time we become aware that the child is struggling,” Yeh said. “We are seeing issues like intentional medication overdose, referrals after other self-harm actions, or even the discovery of a note indicating the intention to do harm to self.”

Suicide deaths among 10- to 14-year-olds tripled between 2007 and 2018 and held steady through 2021, with rates climbing even among children as young as 8 years, according to a research in JAMA Network Open. Meanwhile, one in five high school students seriously contemplated suicide in 2023 (27% girls, 14% boys).

 

Mental Health Strategies for Kids in Primary Care

While pediatricians cannot replace a mental health professional, they have the unique advantage of maintaining a long-term relationship with patients. Experts said clinicians should take an active role in supporting the mental health of patients through a variety of evidence-based strategies.

Changing Thought Patterns 

Cognitive-behavioral therapy (CBT) involves identifying and challenging automatic negative thoughts, which can affect a child’s emotional state and lead to behaviors like withdrawal or lashing out.

Yeh recommended asking a child about what is bothering them, pointing out unhelpful and negative thoughts, and then offering a different, positive one instead.

She also often draws a picture of the CBT chart, which is a visual representation of how feelings lead to thoughts, and then behaviors.

“I draw this diagram because it helps give the patients a visual understanding of how their feelings and emotions are connected,” Yeh said.

 

Tools to Tolerate Stressful Situations

Simple tools like breathing exercises, body scanning, and physical exercise can help children better tolerate distress.

Pediatricians can also recommend families use guided meditations, which have been shown to lower anxiety and increase positive social behavior, said Mollie Grow, MD, an associate professor of pediatrics at the University of Washington Medicine and Seattle Children’s Hospital, both in Seattle.

But a child might first need to get negative energy out before they can become calm.

“So I’m like, ‘okay, let’s do actual physical exercise. Give me 10 jumping jacks.’ No one’s nervous after those jumping jacks,” Nguyen said. “When you’ve already been triggered, your nerves have gotten going, and you’re starting to spiral, you can’t slow yourself down enough to do a breathing exercise.”

Nguyen also said that cold water quickly calms the nervous system.

“I’ll run cold water in the office and have them put their hand in it until it’s almost frozen,” and the child or teen is able to think more clearly, Nguyen said. “It’s a real physiological response. It works.”

 

The Origin of a Feeling 

Explaining how symptoms of anxiety, depression, or ADHD work can help children and teens better understand that what they are experiencing is normal and better cope, Yeh said.

Clinicians might teach patients about how shallow breathing — a symptom of anxiety — is a result of the brain scanning for danger, and how slowing breathing tricks the brain into feeling safe again.

 

Barriers Abound

The use of these interventions in pediatric settings is not yet widespread, Grow said.

But starting in July 2025, the Accreditation Council for Graduate Medical Education will require pediatric residencies to include 4 weeks of mental health training. How that requirement is fulfilled will be up to residencies, said Brian Alverson, MD, pediatric program director and vice-chair of education at Nemours Children’s Hospital in Wilmington, Delaware.

Even with training, many pediatricians lack the time to address mental health issues during an office visit, said Carlos Lerner, MD, a professor of clinical pediatrics at University of California, Los Angeles Health. And despite low or sometimes no reimbursement for discussing these issues with patients, “the reality is we end up doing it anyway.”

Treating issues like anxiety and depression “is a daily, constant part of the care that I provide for my patients,” said Lerner. “Whether the pandemic or social media exacerbated it, we are absolutely seeing a rise in mental health issues.”

A version of this article first appeared on Medscape.com.

A young boy with a habit of screaming when he didn’t get his way is among the patients Joannie Yeh, MD, a primary care physician at Nemours Children’s Health in Media, Pennsylvania, has helped in her practice.

Yeh taught the boy to stretch out his hands into the shape of a starfish, then trace around the edges of his fingers while breathing slowly and deeply. His parents later reported that after using the strategy at home, their son was no longer taking his rage out on his younger siblings.

Interventions like breathing exercises are just a few techniques Yeh hopes more primary care clinicians will teach young patients as mental health issues among this population soar to a national state of emergency, major medical groups say. But many children go without treatment because of shortages of mental health clinicians and long wait-lists for appointments.

“Knowledge of different types of interventions allows pediatricians to offer more options to families — more than just medication alone,” Yeh said. “There are some strategies, like cognitive behavioral therapy, that a therapist is equipped to deliver, but we can help explain them or teach simple skills that borrow from principles of higher-level techniques and can help patients and families while they wait to see a therapist.”

The use of techniques that are based on mindfulness, cognitive behavioral therapy, and psychotherapy are especially helpful to pediatricians after a child’s answers on a screener indicate they may be struggling with anxiety, depression, or attention-deficit/hyperactivity disorder (ADHD), said Theresa Nguyen, MD, chair of pediatrics at Greater Baltimore Medical Center, Baltimore.

“It kind of sucks if you come in worried and then your doctor says, ‘Okay, let me send you to a psychiatrist who you can’t see for 6 months; let me send you to a therapist who’s going to take a couple of weeks to get in with,’” Nguyen said.

Yeh said over the past few years she has cared for more youth coming in as follow-ups after an emergency department visit for a mental health episode.

“Oftentimes, this is the first time we become aware that the child is struggling,” Yeh said. “We are seeing issues like intentional medication overdose, referrals after other self-harm actions, or even the discovery of a note indicating the intention to do harm to self.”

Suicide deaths among 10- to 14-year-olds tripled between 2007 and 2018 and held steady through 2021, with rates climbing even among children as young as 8 years, according to a research in JAMA Network Open. Meanwhile, one in five high school students seriously contemplated suicide in 2023 (27% girls, 14% boys).

 

Mental Health Strategies for Kids in Primary Care

While pediatricians cannot replace a mental health professional, they have the unique advantage of maintaining a long-term relationship with patients. Experts said clinicians should take an active role in supporting the mental health of patients through a variety of evidence-based strategies.

Changing Thought Patterns 

Cognitive-behavioral therapy (CBT) involves identifying and challenging automatic negative thoughts, which can affect a child’s emotional state and lead to behaviors like withdrawal or lashing out.

Yeh recommended asking a child about what is bothering them, pointing out unhelpful and negative thoughts, and then offering a different, positive one instead.

She also often draws a picture of the CBT chart, which is a visual representation of how feelings lead to thoughts, and then behaviors.

“I draw this diagram because it helps give the patients a visual understanding of how their feelings and emotions are connected,” Yeh said.

 

Tools to Tolerate Stressful Situations

Simple tools like breathing exercises, body scanning, and physical exercise can help children better tolerate distress.

Pediatricians can also recommend families use guided meditations, which have been shown to lower anxiety and increase positive social behavior, said Mollie Grow, MD, an associate professor of pediatrics at the University of Washington Medicine and Seattle Children’s Hospital, both in Seattle.

But a child might first need to get negative energy out before they can become calm.

“So I’m like, ‘okay, let’s do actual physical exercise. Give me 10 jumping jacks.’ No one’s nervous after those jumping jacks,” Nguyen said. “When you’ve already been triggered, your nerves have gotten going, and you’re starting to spiral, you can’t slow yourself down enough to do a breathing exercise.”

Nguyen also said that cold water quickly calms the nervous system.

“I’ll run cold water in the office and have them put their hand in it until it’s almost frozen,” and the child or teen is able to think more clearly, Nguyen said. “It’s a real physiological response. It works.”

 

The Origin of a Feeling 

Explaining how symptoms of anxiety, depression, or ADHD work can help children and teens better understand that what they are experiencing is normal and better cope, Yeh said.

Clinicians might teach patients about how shallow breathing — a symptom of anxiety — is a result of the brain scanning for danger, and how slowing breathing tricks the brain into feeling safe again.

 

Barriers Abound

The use of these interventions in pediatric settings is not yet widespread, Grow said.

But starting in July 2025, the Accreditation Council for Graduate Medical Education will require pediatric residencies to include 4 weeks of mental health training. How that requirement is fulfilled will be up to residencies, said Brian Alverson, MD, pediatric program director and vice-chair of education at Nemours Children’s Hospital in Wilmington, Delaware.

Even with training, many pediatricians lack the time to address mental health issues during an office visit, said Carlos Lerner, MD, a professor of clinical pediatrics at University of California, Los Angeles Health. And despite low or sometimes no reimbursement for discussing these issues with patients, “the reality is we end up doing it anyway.”

Treating issues like anxiety and depression “is a daily, constant part of the care that I provide for my patients,” said Lerner. “Whether the pandemic or social media exacerbated it, we are absolutely seeing a rise in mental health issues.”

A version of this article first appeared on Medscape.com.

Exposure to Agent Orange and depleted urology are associated with increased risk of bladder cancer, according to a recent Urology meta-analysis. About 3200 US veterans are diagnosed with bladder cancer each year, which is the fourth most diagnosed cancer among veterans. “Identifying veterans exposed to these risk factors is crucial for implementing screening protocols and connecting them with preventive healthcare measures when possible,” the authors said. 

A meta-analysis using narrative synthesis to incorporate diverse studies examined the impact of exposure to Agent Orange, depleted uranium exposure, contaminated drinking water, and other environmental contaminants. The researchers found 7 studies of Agent Orange exposure that in total showed a statistically significant increase in bladder cancer risk (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.01-1.36; P < .001) among 2,705,283 veterans. Six studies revealed that depleted uranium exposure caused a statistically significant association with bladder cancer as well (HR, 2.13; 95% CI, 1.31-3.48; P = .002) among 28,899 patients. Exposure to contaminated drinking water exposure in 4 studies also suggested an increased bladder cancer risk (HR, 1.25; 95% CI, 0.97-1.61; P = .08) among 370,408 veterans. 

The authors identified other factors that also contributed to increased bladder cancer risk, including smoking, occupational exposures to substances like asbestos and diesel fumes, and exposure to ionizing radiation from nuclear tests. “These findings emphasize the urgent need for enhanced clinical management strategies and preventive measures for veterans exposed to these carcinogenic agents,” the authors asserted. 

The authors report no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Exposure to Agent Orange and depleted urology are associated with increased risk of bladder cancer, according to a recent Urology meta-analysis. About 3200 US veterans are diagnosed with bladder cancer each year, which is the fourth most diagnosed cancer among veterans. “Identifying veterans exposed to these risk factors is crucial for implementing screening protocols and connecting them with preventive healthcare measures when possible,” the authors said. 

A meta-analysis using narrative synthesis to incorporate diverse studies examined the impact of exposure to Agent Orange, depleted uranium exposure, contaminated drinking water, and other environmental contaminants. The researchers found 7 studies of Agent Orange exposure that in total showed a statistically significant increase in bladder cancer risk (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.01-1.36; P < .001) among 2,705,283 veterans. Six studies revealed that depleted uranium exposure caused a statistically significant association with bladder cancer as well (HR, 2.13; 95% CI, 1.31-3.48; P = .002) among 28,899 patients. Exposure to contaminated drinking water exposure in 4 studies also suggested an increased bladder cancer risk (HR, 1.25; 95% CI, 0.97-1.61; P = .08) among 370,408 veterans. 

The authors identified other factors that also contributed to increased bladder cancer risk, including smoking, occupational exposures to substances like asbestos and diesel fumes, and exposure to ionizing radiation from nuclear tests. “These findings emphasize the urgent need for enhanced clinical management strategies and preventive measures for veterans exposed to these carcinogenic agents,” the authors asserted. 

The authors report no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Exposure to Agent Orange and depleted urology are associated with increased risk of bladder cancer, according to a recent Urology meta-analysis. About 3200 US veterans are diagnosed with bladder cancer each year, which is the fourth most diagnosed cancer among veterans. “Identifying veterans exposed to these risk factors is crucial for implementing screening protocols and connecting them with preventive healthcare measures when possible,” the authors said. 

A meta-analysis using narrative synthesis to incorporate diverse studies examined the impact of exposure to Agent Orange, depleted uranium exposure, contaminated drinking water, and other environmental contaminants. The researchers found 7 studies of Agent Orange exposure that in total showed a statistically significant increase in bladder cancer risk (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.01-1.36; P < .001) among 2,705,283 veterans. Six studies revealed that depleted uranium exposure caused a statistically significant association with bladder cancer as well (HR, 2.13; 95% CI, 1.31-3.48; P = .002) among 28,899 patients. Exposure to contaminated drinking water exposure in 4 studies also suggested an increased bladder cancer risk (HR, 1.25; 95% CI, 0.97-1.61; P = .08) among 370,408 veterans. 

The authors identified other factors that also contributed to increased bladder cancer risk, including smoking, occupational exposures to substances like asbestos and diesel fumes, and exposure to ionizing radiation from nuclear tests. “These findings emphasize the urgent need for enhanced clinical management strategies and preventive measures for veterans exposed to these carcinogenic agents,” the authors asserted. 

The authors report no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE:

CD37, a surface protein present on most acute myeloid leukemia (AML) blasts, demonstrates unique internalization properties that enable targeted drug delivery with minimal impact on normal blood cells. Anti-CD37 antibody-drug conjugate (ADC) shows specific cytotoxicity to AML blasts while preserving normal hematopoietic stem cells.

METHODOLOGY:

• Researchers analyzed CD37 expression in 55 untreated, newly diagnosed primary AML samples, along with normal hematopoietic stem cells, peripheral blood mononuclear cells, and AML cell lines.
• Analysis included internalization assays using anti-CD37 antibody conjugated to fluorochrome Alexa Fluor 647, with cells incubated for 2 hours at 37 °C vs on ice to quantify surface and intracellular CD37.
• Investigators conducted in vivo studies using NOD scid gamma mice and NRGS mice treated with 25 mg/mL busulfan, followed by weekly monitoring of disease burden through flow cytometry.

TAKEAWAY:

• CD37 surface expression was identified on all primary AML blasts examined, with varying levels of expression not correlating with European LeukemiaNet classification or overall survival.
• AML blasts demonstrated significantly higher CD37 internalization frequency than normal B cells (P = .001) and monocytes (P = .01), independent of surface expression levels.
• Primary AML samples with activating signaling mutations showed a trend toward increased CD37 internalization frequency (P = .053) than those without signaling mutations.
• Treatment with anti–CD37-DM1 significantly improved clinical outcomes and overall survival in multiple in vivo models of AML while showing minimal toxicity in humanized CD37 knockin mice.

IN PRACTICE:

“CD37 is a surface receptor present on most AML blasts, which has unique internalization properties when compared with normal blood cells. Treatment of AML with anti-CD37 ADC demonstrates specific cytotoxicity in vitro and improved overall survival in vivo,” wrote the authors of the study.

SOURCE:

The study was led by Erin Jeremy and Esthela Artiga, Ohio State University, Columbus. It was published online on January 14 in Blood Advances.

LIMITATIONS:

According to the authors, variations in CD37 expression in response to laboratory manipulations such as Ficoll-Hypaque cell separation and cryopreservation may have affected the detection of CD37 on AML cells with inherently lower levels of expression. The researchers also note that they were unable to associate pathologic characteristics with membrane trafficking and cytotoxic activity within their cohort of samples.

DISCLOSURES:

Karilyn T. Larkin received research funding from Debiopharm. The remaining authors reported no competing financial interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

CD37, a surface protein present on most acute myeloid leukemia (AML) blasts, demonstrates unique internalization properties that enable targeted drug delivery with minimal impact on normal blood cells. Anti-CD37 antibody-drug conjugate (ADC) shows specific cytotoxicity to AML blasts while preserving normal hematopoietic stem cells.

METHODOLOGY:

• Researchers analyzed CD37 expression in 55 untreated, newly diagnosed primary AML samples, along with normal hematopoietic stem cells, peripheral blood mononuclear cells, and AML cell lines.
• Analysis included internalization assays using anti-CD37 antibody conjugated to fluorochrome Alexa Fluor 647, with cells incubated for 2 hours at 37 °C vs on ice to quantify surface and intracellular CD37.
• Investigators conducted in vivo studies using NOD scid gamma mice and NRGS mice treated with 25 mg/mL busulfan, followed by weekly monitoring of disease burden through flow cytometry.

TAKEAWAY:

• CD37 surface expression was identified on all primary AML blasts examined, with varying levels of expression not correlating with European LeukemiaNet classification or overall survival.
• AML blasts demonstrated significantly higher CD37 internalization frequency than normal B cells (P = .001) and monocytes (P = .01), independent of surface expression levels.
• Primary AML samples with activating signaling mutations showed a trend toward increased CD37 internalization frequency (P = .053) than those without signaling mutations.
• Treatment with anti–CD37-DM1 significantly improved clinical outcomes and overall survival in multiple in vivo models of AML while showing minimal toxicity in humanized CD37 knockin mice.

IN PRACTICE:

“CD37 is a surface receptor present on most AML blasts, which has unique internalization properties when compared with normal blood cells. Treatment of AML with anti-CD37 ADC demonstrates specific cytotoxicity in vitro and improved overall survival in vivo,” wrote the authors of the study.

SOURCE:

The study was led by Erin Jeremy and Esthela Artiga, Ohio State University, Columbus. It was published online on January 14 in Blood Advances.

LIMITATIONS:

According to the authors, variations in CD37 expression in response to laboratory manipulations such as Ficoll-Hypaque cell separation and cryopreservation may have affected the detection of CD37 on AML cells with inherently lower levels of expression. The researchers also note that they were unable to associate pathologic characteristics with membrane trafficking and cytotoxic activity within their cohort of samples.

DISCLOSURES:

Karilyn T. Larkin received research funding from Debiopharm. The remaining authors reported no competing financial interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

CD37, a surface protein present on most acute myeloid leukemia (AML) blasts, demonstrates unique internalization properties that enable targeted drug delivery with minimal impact on normal blood cells. Anti-CD37 antibody-drug conjugate (ADC) shows specific cytotoxicity to AML blasts while preserving normal hematopoietic stem cells.

METHODOLOGY:

• Researchers analyzed CD37 expression in 55 untreated, newly diagnosed primary AML samples, along with normal hematopoietic stem cells, peripheral blood mononuclear cells, and AML cell lines.
• Analysis included internalization assays using anti-CD37 antibody conjugated to fluorochrome Alexa Fluor 647, with cells incubated for 2 hours at 37 °C vs on ice to quantify surface and intracellular CD37.
• Investigators conducted in vivo studies using NOD scid gamma mice and NRGS mice treated with 25 mg/mL busulfan, followed by weekly monitoring of disease burden through flow cytometry.

TAKEAWAY:

• CD37 surface expression was identified on all primary AML blasts examined, with varying levels of expression not correlating with European LeukemiaNet classification or overall survival.
• AML blasts demonstrated significantly higher CD37 internalization frequency than normal B cells (P = .001) and monocytes (P = .01), independent of surface expression levels.
• Primary AML samples with activating signaling mutations showed a trend toward increased CD37 internalization frequency (P = .053) than those without signaling mutations.
• Treatment with anti–CD37-DM1 significantly improved clinical outcomes and overall survival in multiple in vivo models of AML while showing minimal toxicity in humanized CD37 knockin mice.

IN PRACTICE:

“CD37 is a surface receptor present on most AML blasts, which has unique internalization properties when compared with normal blood cells. Treatment of AML with anti-CD37 ADC demonstrates specific cytotoxicity in vitro and improved overall survival in vivo,” wrote the authors of the study.

SOURCE:

The study was led by Erin Jeremy and Esthela Artiga, Ohio State University, Columbus. It was published online on January 14 in Blood Advances.

LIMITATIONS:

According to the authors, variations in CD37 expression in response to laboratory manipulations such as Ficoll-Hypaque cell separation and cryopreservation may have affected the detection of CD37 on AML cells with inherently lower levels of expression. The researchers also note that they were unable to associate pathologic characteristics with membrane trafficking and cytotoxic activity within their cohort of samples.

DISCLOSURES:

Karilyn T. Larkin received research funding from Debiopharm. The remaining authors reported no competing financial interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.