The Role of Intraoperative Radiotherapy Treatment of Locally Advanced Rectal Cancer.

Intraoperative radiation therapy (IORT) has been used in the treatment of locally advanced and recurrent rectal cancers for the last several decades. Given the heterogeneity of patients treated and different indications for use and dosing at different institutions, it has been difficult to discern if IORT adds any appreciable benefit to standard of care therapies. Herein, the rationale for IORT in rectal cancer is discussed along with the most modern and best available data in 2023. IORT is likely indicated in patients with locally advanced and locally recurrent rectal cancer with threatened margins (R0 or R1 resection) to help improve local control. High-quality imaging and multidisciplinary discussion are necessary to ensure optimal patient selection. Appropriate counseling of the patient and excellent team communication are of the utmost importance given the challenging nature of these cases and the prognostic implications of R1 and R2 resections in this patient population.

Evolving Standards of Care in the Management of Localized Colorectal Cancer.

The treatment of patients with localized rectal cancer is complex and requires input from a multidisciplinary team. Baseline local staging and mismatch repair protein testing are vital to develop individualized treatment plans. There are multiple options in terms of treatment modalities and sequencing, including transanal excision, short-course radiation, long-course chemoradiation, chemotherapy doublet or triplet, nonoperative management, and immune checkpoint blockade for patients with mismatch repair deficient tumors. While localized colon cancer is typically treated with surgical resection and consideration of adjuvant chemotherapy, emerging data suggest that neoadjuvant chemotherapy may be beneficial in patients with higher-risk disease. Quality-of-life considerations are imperative to prevent potential chronic effects on psychosocial health, neuropathy, fertility, and bowel, bladder, and sexual function. The omission of radiation or surgery can mitigate these toxicities without diminishing oncologic outcomes. The optimal treatment plan and sequence is not a one-size-fits-all approach but rather should be personalized to the patient's disease burden, tumor location, comorbidities, and preferences.

Method to assess the need for re-planning HDR brachytherapy tandem and ring treatments.

High dose rate (HDR) brachytherapy procedures for cervical cancer require multiple applicator insertions for multiple (typically 5) fractions of a single plan, which carries a risk for variability in applicator position between fractions. Due to applicator displacement relative to patient anatomy, the dose to nearby organs-at-risk (OARs) may vary significantly from one fraction to the next. The purpose of this study was to evaluate the effect of changes in HDR tandem and ring (T&R) applicator position on doses to nearby OARs and to present a quick and simple method to estimate doses to OARs inter-fractionally without having to perform a re-plan. Ninety CT image sets for 20 patients, ages 44 to 86, undergoing T&R-based HDR for cervical cancer were used retrospectively for this study. Measures of applicator positional and angular changes relative to the bony anatomy were obtained using image fusion in MIM software, between the planning CT (plan CT) and the CT on the treatment day (CT-TX). Dosimetric data were determined, also using MIM software, using the original (first fraction) dose distribution applied to organs at risk (rectum and bladder), transferred via rigid registration from the plan CT to each CT-TX. Bladder and rectum contours were also transferred from each plan CT to each CT-TX and were tweaked manually to match anatomy on each CT-TX and examined visually for appropriateness. Differences in translation and rotation of the T&R applicator between the planning CT and subsequent individual fractions were recorded and plotted against dose differences between each fraction of treatment and the original (first) fraction. Absolute dose (D2cc) and volume (V50) differences vs positional shifts were calculated and plotted, and the Pearson Product-Moment correlation coefficient between dose parameters and measured positional shifts was determined. Average dosimetric differences between planned dose and subsequent fractional doses obtained through rigid registration were 1.48 ± 1.92 Gy, 14.91 ± 11.92 cm3, 0.56 ± 0.93 Gy, and 1.77 ± 2.18 cm3 for Bladder D2cc, Bladder V50, Rectum D2cc, and Rectum V50, respectively. Correlation between Bladder V50 and sagittal plane rotation gave an r2 of 0.4, showing the most correlation of all parameters studied. Bladder dose and volume increased by a maximum of about 2.7 Gy and 50 cm3 overall for Bladder D2cc and Bladder V50, respectively. Bladder V50 was most sensitive to T&R applicator displacements. We have quantified the effects of applicator positional changes on dose changes for the bladder and rectum. Even large changes in applicator position between fractions did not result in significant changes in dose to these normal tissues, indicating that adaptive re-planning is not necessary.

Not all stage I and II endometrial cancers are created equal: Recurrence-free survival and cause-specific survival after observation or vaginal brachytherapy alone in all subgroups of early-stage high-intermediate and high-risk endometrial cancer.

OBJECTIVE: To evaluate recurrence-free survival (RFS) and cause-specific survival (CSS) after observation or vaginal brachytherapy (VB) alone in all subgroups of early-stage high-intermediate (HIR) and high-risk endometrial cancer (EC). METHODS: We identified patients with stage I HIR (GOG-249 criteria) and stage II endometrioid EC, and stage I and II non-endometrioid EC who underwent surgery at Mayo Clinic and Cleveland Clinic between 1999 and 2016. Three-year RFS and CSS after observation or VB only were estimated in 16 subgroups defined by risk factors. RESULTS: Among 4156 ECs, we identified 447 (10.8%) stage I endometrioid HIR, 52 (1.3%) stage II endometrioid, 350 (8.4%) stage I non-endometrioid, and 17 (0.4%) stage II non-endometrioid ECs; observation or VB alone was applied in 349 (78.1%), 24 (46.2%), 187 (53.4%), and 2 (11.8%) patients, respectively. After observation or VB, stage I HIR endometrioid EC subgroups with <2 factors among grade 3, LVSI, or stage IB had a 3-year CSS >95% (lower 95% confidence intervals limit: 89.8%), whereas subgroups with ≥2 factors had poorer outcomes. No EC-related deaths after 3 years were reported in 97 stage IA non-endometrioid ECs without myometrial invasion. Stage II ECs had poor outcomes regardless of histology. CONCLUSIONS: Observation or VB only may be sufficient in stage I endometrioid HIR ECs with <2 factors among grade 3, LVSI, or IB and in stage IA non-endometrioid ECs without myometrial invasion. Stratification of early-stage HIR and high-risk ECs into risk subgroups potentially alleviates the overtreatment and undertreatment risk and should be considered in future research.

Development and validation of a comprehensive clinical risk-scoring model for prediction of overall survival in patients with endometrioid endometrial carcinoma.

OBJECTIVE: To develop and validate a comprehensive overall survival (OS) risk-scoring model in women with endometrioid endometrial cancer (EC). METHODS: Patients with EC diagnosed from 2004 to 2013 were identified through the National Cancer Database (NCDB). Patients with known lymphovascular space invasion (LVSI) status who were treated surgically (with or without adjuvant therapy) were included. Cox proportional hazards analysis was used to identify prognostic factors for OS. This model was used to assign points based on hazard ratios for risk factors and a risk score was obtained. Recursive partitioning analysis (RPA) was used to categorize patients into risk groups. Results were internally validated in a cohort of patients from our institution (CCF cohort). Risk scores were calculated and assessed in a Cox regression model, and Harrell's c-index was calculated to assess model fit. RESULTS: Among 349,404 women with EEC during the study period, 42,107 fulfilled inclusion criteria. Factors associated with worse OS were age ≥ 60, African American race, Charlson-Deyo score 1 or 2+, higher grade, LVSI, tumor size ≥2 cm, and no lymphadenectomy performed. Six risk groups were identified (scores 0-30) and OS estimated for each risk group. Risk score per 1-point increase in HR were comparable between NCDB and CCF cohorts (HR 1.21 (1.20-1.22 p < 0.001 vs 1.18 (1.12-1.25), p < 0.001), and c-index 0.80 (0.79-0.81) vs. 0.77 (0.68-0.86). Similar analysis was done in stage IA and IB. Adjuvant therapy had a beneficial effect on survival in the majority of stage IB patients, but only one of the six risk groups in stage IA EC. CONCLUSIONS: We report a comprehensive validated OS risk-scoring model for patients with.

Stereotactic body radiotherapy for the treatment of oligometastatic gynecological malignancy in the abdomen and pelvis: A single-institution experience.

PURPOSE/OBJECTIVES: Metastasis-directed therapy with stereotactic body radiotherapy (SBRT) in the setting of oligometastatic disease is a rapidly evolving paradigm given ongoing improvements in systemic therapies and diagnostic modalities. However, SBRT to targets in the abdomen and pelvis is historically associated with concerns about toxicity. The purpose of this study was to evaluate the safety and efficacy of SBRT to the abdomen and pelvis for women with oligometastases from primary gynecological tumors. MATERIALS/METHODS: From our IRB-approved registry, all patients who were treated with SBRT between 2014 and 2020 were identified. Oligometastatic disease was defined as 1 to 5 discrete foci of clinical metastasis radiographically diagnosed by positron emission tomography (PET) and/or computerized tomography (CT) imaging. The primary endpoint was local control at 12 months. Local and distant control rates were estimated using the Kaplan-Meier method. Time intervals for development of local progression and distant progression were calculated based on follow up visits with re-staging imaging. Acute and late toxicity outcomes were determined based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: We identified 34 women with 43 treated lesions. Median age was 68 years (range 32-82), and median follow up time was 12 months (range 0.2-54.0). Most common primary tumor sites were ovarian (n=12), uterine (n=11), and cervical (n=7). Median number of previous lines of systemic therapy agents at time of SBRT was 2 (range 0-10). Overall, SBRT was delivered to 1 focus of oligometastasis in 29 cases, 2 foci in 2 cases, 3 foci in 2 cases, and 4 foci in 1 case. All patients were treated comprehensively with SBRT to all sites of oligometastasis. Median prescription dose was 24 Gy (range 18-54 Gy) in 3 fractions (range 3-6) to a median prescription isodose line of 83.5% (range 52-95). Local control by lesion at 12 and 24 months was 92.5% for both time points. Local failure was observed in three treated sites among two patients, two of which were at 11 months in one patient, and the other at 30 months. Systemic control rate was 60.2% at 12 months. Overall survival at 12 and 24 months was 85% and 70.2%, respectively. Acute grade 2 toxicities included nausea (n=3), and there were no grade > 3 acute toxicities. Late grade 1 toxicities included diarrhea (n=1) and fatigue (n=1), and there were no grade > 2 toxicities. CONCLUSION: SBRT to oligometastatic gynecologic malignancies in the abdomen and pelvis is feasible with encouraging preliminary safety and local control outcomes. This approach is associated with excellent local control and low rates of toxicity during our follow-up interval. Further investigations into technique, dose-escalation and utilization are warranted.

Can normalized carcinoembryonic antigen following neoadjuvant chemoradiation predict tumour recurrence after curative resection for locally advanced rectal cancer?

AIM: The aim of this work was to evaluate whether normalized carcinoembryonic antigen (CEA) following neoadjuvant chemoradiation predicts the prognosis following curative resection in locally advanced rectal cancer. METHOD: Patients who underwent neoadjuvant chemoradiation and curative resection for locally advanced rectal cancer between 2010 and 2015 were divided into three groups: Group A (n = 119, normal-to-normal): normal CEA before and after neoadjuvant chemoradiation; Group B (n = 37, high-to-normal): elevated CEA before and normal CEA after neoadjuvant chemoradiation; Group C (n = 36, high-to-high): elevated CEA before and after neoadjuvant chemoradiation. Overall and disease-free survival were compared. Univariate and multivariate analyses identified potential predictors for recurrence. RESULTS: One hundred and ninety two patients [median age 59 years (range 31-87), 65.1% male] were identified: 54.7% had low rectal cancer: 12.5% were clinical stage T4 and 70.3% were clinically node positive; 21.9% achieved complete pathological response; 24.5% had abdominoperineal resection (APR); and 70.3% underwent adjuvant chemotherapy following curative resection. Significantly more patients in Group C underwent APR (p = 0.0209), had advanced pathological T stage (P = 0.0065) and a higher prevalence of perineural invasion (p = 0.0042). Overall and disease-free survival were significantly higher for Group A than for Group C [hazard ratio (HR) = 4.32, 95% CI = 1.66-11.21, p = 0.0026 and HR=2.68, 95% CI = 1.33-5.40, p = 0.0057, respectively]. No significant difference was noted between Groups A and B for overall (p = 0.0591) or disease-free (p = 0.2834) survival. Another risk factor associated with recurrence and death was clinical T4 stage; nodal positivity was a risk factor only for recurrence. CONCLUSION: Elevated CEA after neoadjuvant chemoradiation and clinical stage T4 disease were unfavourable predictors for overall and disease-free survival. Normalized CEA during neoadjuvant chemoradiation may serve as a prognosticator, although pretreatment CEA may significantly affect survival.

Impact of vaginal brachytherapy on survival in stage I endometrioid endometrial carcinoma.

OBJECTIVE: To evaluate trends in use of radiation therapy and its impact on overall survival in low- and high-grade stage I endometrioid endometrial carcinoma. METHODS: Patients with stage I endometrial cancer who underwent hysterectomy from 2004 to 2013 were identified through the National Cancer Database and classified as: stage IA G1/2, stage IA G3, stage IB G1/2, and stage IB G3. Trends in use of vaginal brachytherapy and external beam radiation therapy were assessed. Overall survival was measured from surgery and estimated using the Kaplan-Meier method. The effect of radiation therapy on overall survival was assessed within each stage/grade group using Cox proportional hazards analysis in propensity-matched treatment groups. RESULTS: A total of 132 393 patients met inclusion criteria, and 81% of patients had stage IA and 19% had stage IB endometrial cancer. Adjuvant therapy was administered in 18% of patients: 52% received vaginal brachytherapy, 30% external beam radiation therapy, and 18% chemotherapy ±radiation therapy. External beam radiation therapy use decreased from 9% in 2004 to 4% in 2012, while vaginal brachytherapy use increased from 8% to 14%. Stage IA G1/2 patients did not benefit from either external beam radiation therapy or vaginal brachytherapy, while administration of vaginal brachytherapy improved overall survival in stage IB G1/2 compared with no treatment (p<0.0001). In stage IB G1/2 and stage IA G3, vaginal brachytherapy was superior to external beam radiation therapy (p=0.0004 and p=0.004, respectively). Stage IB G3 patients had improved overall survival with either vaginal brachytherapy or external beam radiation therapy versus no treatment but no difference in overall survival was seen between vaginal brachytherapy and external beam radiation therapy (p=0.94). CONCLUSIONS: The delivery of adjuvant radiation therapy in patients with stage IA G1/2 endometrial carcinoma is not associated with improvement in overall survival. Patients with stage IB G1/2 and G3 as well as stage IA G3 are shown to benefit from improved overall survival when adjuvant radiation therapy is administered. These findings demonstrate potential opportunities to reduce both overtreatment and undertreatment in stage I endometrial cancer patients.

Undifferentiated endometrial carcinoma: a National Cancer Database analysis of prognostic factors and treatment outcomes.

BACKGROUND: Undifferentiated endometrioid endometrial carcinoma of the uterus is a rare, highly aggressive, and under-recognized subtype of endometrial cancer. OBJECTIVE: This study evaluates survival, prognostic factors for survival, and treatment outcomes associated with undifferentiated endometrial cancer. METHODS: The National Cancer Database was queried to identify patients with undifferentiated endometrial cancer who underwent definitive primary surgical treatment. Patients with all other histologic subtypes or incomplete treatment data were excluded. Univariable and multivariable Cox proportional hazards analyses were used to determine independent prognostic factors for survival. Points for each prognostic factor were assigned from regression coefficients in the final multivariable model and summed for a total score. Recursive partitioning analysis was used to determine cut-offs in the score to identify unique prognostic groups. RESULTS: Among 349 404 women diagnosed with endometrial cancer from 2004 to 2013, 3994 (1.1%) met the criteria for diagnosis of undifferentiated endometrial cancer and 3486 had survival data. Median age at diagnosis was 65 years (interquartile range (IQR) 57-74) and 58% of patients had early stage disease. Median interval from diagnosis to surgery was 3.7 weeks (IQR 2.0-5.7). Five year overall survival was 57% (standard error (SE) 1%). Stage was the strongest predictor of survival, with a 15-20% decrement in 5 year survival for each advance in stage. Stage, age, race, and presence of comorbidities were independent predictors of survival and were used to categorize patients into five prognostic groups. Adjuvant therapy was associated with improved survival across most disease stages and prognostic groups. Multimodal adjuvant therapy was superior to unimodal treatment particularly in advanced stage unfavorable and very unfavorable groups. CONCLUSION: In women with undifferentiated endometrial cancer, survival is primarily driven by stage. Despite the poor overall prognosis of undifferentiated endometrial cancer, multimodal adjuvant therapy is a key component of treatment.

Oncological Outcomes of Patients with Locally Advanced Rectal Cancer and Lateral Pelvic Lymph Node Involvement.

INTRODUCTION: The optimal management of patients with radiologically positive lateral pelvic lymph nodes in locally advanced rectal cancer remains unclear. We compared local recurrence rates and oncological outcomes of patients with locally advanced cancer with and without lateral pelvic lymph nodes. METHODS: Patients who underwent curative surgery for stage III rectal adenocarcinoma between 2009 and 2014 and had a preoperative MRI at our institution as well as preoperative neoadjuvant treatment were included. Patients with positive lateral pelvic lymph nodes (iliac or obturator nodes) on preoperative MRI (LPND +) were compared to patients with no lateral pelvic nodal disease (LPND -). Data were collected from a prospectively maintained institutional database. Differences between the groups were compared in univariate analysis. Log-rank test was used to evaluate overall and disease-free survival between the groups. RESULTS: A total of 125 patients met inclusion criteria with a mean age of 56.3 ± 12.2 and 75% were male. Median follow-up was 44 months (IQR 32, 106). Positive LPND was present on preoperative MRI in 43/125 (34.4%) patients who were in the LPND (+) group. Seventeen out of 43 patients had a post-neoadjuvant treatment MRI and 15 patients had a decrease in size of nodes or disappearance of LPND. On univariate analysis, LPND (+) and LPND (-) groups were comparable. Local recurrence rates were higher in the LPND (+) group, although this was not statistically significant (16.3% vs. 6%, p = 0.06). Overall and disease-free survival rates were comparable between the LPND (+) and LPND (-) groups (p = 0.97, p = 0.51). CONCLUSIONS: Management of patients with advanced rectal cancer and radiologically positive lateral pelvic lymph nodes is challenging due to high local recurrence rates. Further studies are needed to develop care pathways for the optimal treatment processes.

Multidisciplinary Conference and Clinical Management of Rectal Cancer.

BACKGROUND: Presentation of rectal cancer cases at a colorectal cancer multidisciplinary conference (CRC-MDC) is a required standard for the newly formed National Accreditation Program for Rectal Cancer administered by the Commission on Cancer. The aim of this study was to determine the frequency and manner in which CRC-MDC changed the management of rectal cancer patients at a tertiary academic center. STUDY DESIGN: All rectal cancer cases presented at a weekly CRC-MDC between July 2015 and June 2016 were prospectively included. Patient demographics and clinical information were recorded. The presenting physician completed a uniform written questionnaire outlining any changes in management as a result of the discussion. RESULTS: There were 408 rectal cancer cases included, and survey responses were obtained for 371 (91%). Thirty-nine patients (11%) had stage IV disease and 20 (5%) had locally recurrent cancer. There was a documented change in plan as a result of the CRC-MDC discussion in 97 of 371 (26%) cases surveyed. Changes in management included a change in therapy or change in therapy sequence in 76 cases, and recommendation of additional evaluation in 36 cases. Rates of management change were similar regardless of surgeon experience. Changes occurred in 23%, 28%, and 26% of cases presented by surgeons with <10, 10 to 20, and >20 years of experience, respectively (chi-square p = 0.63). CONCLUSIONS: The CRC-MDC changes clinical management for a significant portion of rectal cancer patients at a tertiary center, independent of the presenting surgeon's years of clinical experience. Our results support the CRC-MDC standard for the National Accreditation Program for Rectal Cancer.

Multidisciplinary Clinics for Colorectal Cancer Care Reduces Treatment Time.

INTRODUCTION: Management of locally advanced and metastatic colorectal cancer (CRC) requires the expertise of multiple specialists. Multidisciplinary clinics (MDCs) are a working model designed to facilitate delivery of coordinated care. The present study evaluated the effects of MDC on the time to treatment (TTT). PATIENTS AND METHODS: Patients with CRC or locally advanced anal cancer who were evaluated at a single-institution MDC from January 2014 to October 2015 were identified from an institutional registry. The clinical characteristics and timelines for various aspects of treatment were retrospectively reviewed and recorded. A control population of patients not evaluated at the MDC was matched 1:2 by disease and the number of treating specialties. The primary endpoints were the TTT from diagnosis and the TTT from the first consultation. RESULTS: A total of 105 patients were included: 35 were evaluated at the MDC and 70 were controls. The MDC patients experienced a 7.8-day shorter TTT from the first consultation (21.5 vs. 29.3 days; P = .01). The difference was greater for patients visiting 3 departments (21.3 vs. 30.6 days; P < .001). Patients requiring neoadjuvant chemoradiation accounted for most of the decreased interval compared with those requiring surgery alone as their first treatment. The proportion of patients initiating treatment within 3 weeks from the first consultation was greater for those seen in the MDC (57.1% vs. 30% for controls; P = .01). CONCLUSION: Implementation of a multidisciplinary CRC clinic yielded decreased intervals from the first consultation to treatment in our institution. Focusing efforts to increase MDC usage will improve treatment efficiency and improve patient access.

Radiation Therapy in the Management of Soft Tissue Sarcoma: A Clinician's Guide to Timing, Techniques, and Targets.

Radiation therapy represents a vital component in the multidisciplinary management of soft tissue sarcomas. Combined with limb-preserving surgery, radiation therapy represents a standard of care treatment option for patients with high-grade sarcomas. Radiation therapy for soft tissue sarcoma continues to evolve with changes in timing, techniques, and targets. Over the past 2 decades, increasing data have supported the role of preoperative radiotherapy with the potential for lower total doses of radiation and improved long-term function coming at the cost of increased wound complications for certain locations. Retroperitoneal sarcomas represent a location where preoperative treatment is becoming the standard of care based on anatomic constraints and challenges with delivering postoperative radiotherapy. Multiple radiation therapy techniques exist to deliver treatment; currently both 3-dimensional conformal radiotherapy and intensity-modulated radiation therapy (IMRT) are appropriate options, although increasing data support the role of IMRT in reducing dose to critical structures (bone, bowel, kidneys, vessels) while maintaining target coverage. Traditional target volumes have included larger fields; however, recent prospective data have demonstrated that image guidance in conjunction with smaller treatment volumes may reduce toxicity while not increasing marginal failures, although follow-up is short. Because of the toxicity associated with treatment, novel radiotherapy strategies are being used such as stereotactic radiotherapy as well as the use of tumor genetics to identify patients most likely to benefit most from radiotherapy.

The impact of combined radiation and chemotherapy on outcome in uterine papillary serous carcinoma compared to chemotherapy alone.

OBJECTIVE: To investigate the impact of pelvic radiation on survival in patients with uterine serous carcinoma (USC) who received adjuvant chemotherapy. METHODS: Patients with stage I-IV USC were identified from the Surveillance, Epidemiology, and End Results program 2000 to 2009. Patients were included if treated with surgery and chemotherapy. Patients were divided into two groups: those who received chemotherapy and pelvic radiation therapy (CT_RT) and those who received chemotherapy only (CT). Kaplan-Meier curves and Cox regression proportional hazard models were used. RESULTS: Of the 1,838 included patients, 1,272 (69%) were CT and 566 (31%) were CT_RT. Adjuvant radiation was associated with significant improvement in overall survival (OS; p<0.001) and disease-specific survival (DSS; p<0.001) for entire cohort. These findings were consistent for the impact of radiation on OS (p<0.001) and DSS (p<0.001) in advanced stage (III-IV) disease but not for early stage (I?II) disease (p=0.21 for OS and p=0.82 for DSS). In multivariable analysis adjusting for age, stage, race and extent of lymphadenectomy, adjuvant radiation was a significant predictor of OS and DSS for entire cohort (p=0.003 and p=0.05) and in subset of patients with stage III (p=0.02 and p=0.07) but not for patients with stage I (p=0.59 and p=0.49), II (p=0.83 and p=0.82), and IV USC (p=0.50 and p=0.96). Other predictors were stage, positive cytology, African American race and extent of lymphadenectomy. CONCLUSION: In USC patients who received adjuvant chemotherapy, adjuvant radiation was associated with significantly improved outcome in stage III disease but not for other stages. Positive cytology, extent of lymphadenectomy and African race were significant predictors of outcome.

Effects of the 2011 duty hour reforms on interns and their patients: a prospective longitudinal cohort study.

IMPORTANCE: In 2003, the first phase of duty hour requirements for US residency programs recommended by the Accreditation Council for Graduate Medical Education (ACGME) was implemented. Evidence suggests that this first phase of duty hour requirements resulted in a modest improvement in resident well-being and patient safety. To build on these initial changes, the ACGME recommended a new set of duty hour requirements that took effect in July 2011. OBJECTIVE: To determine the effects of the 2011 duty hour reforms on first-year residents (interns) and their patients. DESIGN: As part of the Intern Health Study, we conducted a longitudinal cohort study comparing interns serving before (2009 and 2010) and interns serving after (2011) the implementation of the new duty hour requirements. SETTING: Fifty-one residency programs at 14 university and community-based GME institutions. PARTICIPANTS: A total of 2323 medical interns. MAIN OUTCOME MEASURES: Self-reported duty hours, hours of sleep, depressive symptoms, well-being, and medical errors at 3, 6, 9, and 12 months of the internship year. RESULTS: Fifty-eight percent of invited interns chose to participate in the study. Reported duty hours decreased from an average of 67.0 hours per week before the new rules to 64.3 hours per week after the new rules were instituted (P < .001). Despite the decrease in duty hours, there were no significant changes in hours slept (6.8 → 7.0; P = .17), depressive symptoms (5.8 → 5.7; P = .55) or well-being score (48.5 → 48.4; P = .86) reported by interns. With the new duty hour rules, the percentage of interns who reported concern about making a serious medical error increased from 19.9% to 23.3% (P = .007). CONCLUSIONS AND RELEVANCE: Although interns report working fewer hours under the new duty hour restrictions, this decrease has not been accompanied by an increase in hours of sleep or an improvement in depressive symptoms or well-being but has been accompanied by an unanticipated increase in self-reported medical errors.

Dosimetric analysis of radiation-induced gastric bleeding.

PURPOSE: Radiation-induced gastric bleeding has been poorly understood. In this study, we described dosimetric predictors for gastric bleeding after fractionated radiation therapy. METHODS AND MATERIALS: The records of 139 sequential patients treated with 3-dimensional conformal radiation therapy (3D-CRT) for intrahepatic malignancies were reviewed. Median follow-up was 7.4 months. The parameters of a Lyman normal tissue complication probability (NTCP) model for the occurrence of ≥grade 3 gastric bleed, adjusted for cirrhosis, were fitted to the data. The principle of maximum likelihood was used to estimate parameters for NTCP models. RESULTS: Sixteen of 116 evaluable patients (14%) developed gastric bleeds at a median time of 4.0 months (mean, 6.5 months; range, 2.1-28.3 months) following completion of RT. The median and mean maximum doses to the stomach were 61 and 63 Gy (range, 46-86 Gy), respectively, after biocorrection of each part of the 3D dose distributions to equivalent 2-Gy daily fractions. The Lyman NTCP model with parameters adjusted for cirrhosis predicted gastric bleed. Best-fit Lyman NTCP model parameters were n=0.10 and m=0.21 and with TD50 (normal) = 56 Gy and TD50 (cirrhosis) = 22 Gy. The low n value is consistent with the importance of maximum dose; a lower TD50 value for the cirrhosis patients points out their greater sensitivity. CONCLUSIONS: This study demonstrates that the Lyman NTCP model has utility for predicting gastric bleeding and that the presence of cirrhosis greatly increases this risk. These findings should facilitate the design of future clinical trials involving high-dose upper abdominal radiation.

Under-representation of women in high-impact published clinical cancer research.

BACKGROUND: Adequate representation of women in research has been deemed essential. METHODS: Cancer research published in 8 journals in 2006 was reviewed. The percentage of women among study participants was compared with the proportion expected from population-based estimates of sex-specific cancer incidence, using binomial tests. Differences were assessed in sex distribution of participants by funding source, author sex, and focus of research with the Student t test, and in a linear regression model controlling for cancer type. RESULTS: A total of 1534 cancer research articles were identified, of which 661 (representing 1,096,098 participants) were prospective clinical studies and were analyzed further. For all 7 non-sex-specific cancer types assessed, the majority of studies analyzed included a lower proportion of women than the proportion of women among patients having cancer of that type in the general population. Among studies focusing on cancer treatment, women constituted a significantly lower overall proportion of the participants in the analyzed studies than expected for 6 of 7 non-sex-specific cancer types (P < .001). Among non-sex-specific studies, the mean percentage of participants who were women was 38.8%. Non-sex-specific studies reporting government funding had a higher percentage of female participants (mean 41.3% vs 36.9%; P = .005). In a regression model controlling for cancer type, lack of government funding (P = .03) and focus on cancer treatment (P = .03) were found to be independent significant predictors of a lower percentage of female participants. CONCLUSIONS: Women were under-represented as participants in recently published, high-impact studies of non-sex-specific cancers. Studies that received government funding included a higher proportion of female subjects.

Frequency, nature, effects, and correlates of conflicts of interest in published clinical cancer research.

BACKGROUND: Relationships between clinical researchers and industry are becoming increasingly complex. The frequency and impact of conflicts of interest in the full range of high-impact, published clinical cancer research is unknown. METHODS: The authors reviewed cancer research published in 8 journals in 2006 to determine frequency of self-reported conflicts of interest, source of study funding, and other characteristics. They assessed associations between the likelihood of conflicts of interest and other characteristics by using chi-squared testing. They also compared the likelihood of positive outcome in randomized trials with and without conflicts of interest by chi-squared testing. RESULTS: The authors identified 1534 original oncology studies; 29% had conflicts of interest (including industrial funding) and 17% declared industrial funding. Conflicts of interest varied by discipline (P < .001), continental origin (P < .001), and sex (P < .001) of the corresponding author and were most likely in articles with corresponding authors from departments of medical oncology (45%), those from North America (33%), and those with male first and senior authors (37%). Frequency of conflicts also varied considerably depending upon disease site studied. Studies with industrial funding were more likely to focus on treatment (62% vs 36%; P < .001), and randomized trials that assessed survival were more likely to report positive survival outcomes when a conflict of interest was present (P = .04). CONCLUSIONS: Conflicts of interest characterize a substantial minority of clinical cancer research published in high-impact journals. Therefore, attempts to disentangle the cancer research effort from industry merit further attention, and journals should embrace both rigorous standards of disclosure and heightened scrutiny when conflicts exist.