Brian K. Bednarski

Increasing Disparities in the Age-Related Incidences of Colon and Rectal Cancers in the United States, 1975-2010

IMPORTANCE The overall incidence of colorectal cancer (CRC) has been decreasing since 1998 but there has been an apparent increase in the incidence of CRC in young adults. OBJECTIVE To evaluate age-related disparities in secular trends in CRC incidence in the United States. DESIGN, SETTING, AND PATIENTS A retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) CRC registry. Age at diagnosis was analyzed in 15-year intervals starting at the age of 20 years. SEER*Stat was used to obtain the annual cancer incidence rates, annual percentage change, and corresponding P values for the secular trends. Data were obtained from the National Cancer Institutes SEER registry for all patients diagnosed as having colon or rectal cancer from January 1, 1975, through December 31, 2010 (N = 393 241). MAIN OUTCOME AND MEASURE Difference in CRC incidence by age. RESULTS The overall age-adjusted CRC incidence rate decreased by 0.92% (95% CI, -1.14 to -0.70) between 1975 and 2010. There has been a steady decline in the incidence of CRC in patients age 50 years or older, but the opposite trend has been observed for young adults. For patients 20 to 34 years, the incidence rates of localized, regional, and distant colon and rectal cancers have increased. An increasing incidence rate was also observed for patients with rectal cancer aged 35 to 49 years. Based on current trends, in 2030, the incidence rates for colon and rectal cancers will increase by 90.0% and 124.2%, respectively, for patients 20 to 34 years and by 27.7% and 46.0%, respectively, for patients 35 to 49 years. CONCLUSIONS AND RELEVANCE There has been a significant increase in the incidence of CRC diagnosed in young adults, with a decline in older patients. Further studies are needed to determine the cause for these trends and identify potential preventive and early detection strategies.

Risk-Adjusted Pathologic Margin Positivity Rate As a Quality Indicator in Rectal Cancer Surgery

Purpose Margin positivity after rectal cancer resection is associated with poorer outcomes. We previously developed an instrument for calculating hospital risk-adjusted margin positivity rate (RAMP) that allows identification of performance-based outliers and may represent a rectal cancer surgery quality metric. Methods This was an observational cohort study of patients with rectal cancer within the National Cancer Data Base (2003 to 2005). Hospital performance was categorized as low outlier (better than expected), high outlier (worse than expected), or non-RAMP outlier using standard observed-to-expected methodology. The association between outlier status and overall risk of death at 5 years was evaluated using Cox shared frailty modeling. Results Among 32,354 patients with cancer (mean age, 63.8 ± 13.2 years; 56.7% male; 87.3% white) treated at 1,349 hospitals (4.9% high outlier, 0.7% low outlier), 5.6% of patients were treated at high outliers and 3.0% were treated at low outliers. Various structural (...

Hyperfractionated accelerated reirradiation for rectal cancer: An analysis of outcomes and toxicity ☆

BACKGROUND AND PURPOSE To evaluate outcomes and toxicity in patients treated with hyperfractionated pelvic reirradiation for recurrent rectal cancer. MATERIALS AND METHODS 102 patients with recurrent rectal adenocarcinoma were treated with pelvic reirradiation with a hyperfractionated accelerated approach, consisting of 1.5Gy twice daily fractions to a total dose of 30-45Gy (median 39Gy), with the most common total dose 39Gy (n=90, 88%). The median dose of prior pelvic radiation therapy (RT) was 50.4Gy (range: 25-63Gy). RESULTS The median follow-up was 40months for living patients (range, 3-150months). The 3-year freedom from local progression (FFLP) rate was 40% and the 3-year overall survival (OS) rate was 39%. Treatment with surgery was significantly associated with improved FFLP and OS, with 3-year FFLP rate of 49% vs. 30% (P=0.013), and 3-year OS rate of 62% vs. 20% (P<0.0001), compared to those without surgery. The actuarial 3-year rate of grade 3-4 late toxicity was 34%; patients who underwent surgery had a significantly higher rate of grade 3-4 late toxicity compared to those without surgery (54% vs. 16%, P=0.001). CONCLUSIONS This large, retrospective, single-institution study shows that hyperfractionated accelerated reirradiation was well tolerated. The rate of FFLP was promising, given that the study comprised heavily pre-treated patients with recurrences. Rates of FFLP and OS were particularly impressive in patients who underwent both reirradiation and surgery.

DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics

PURPOSE DNA mismatch repair deficiency (dMMR) hallmarks consensus molecular subtype 1 of colorectal cancer. It is being routinely tested, but little is known about dMMR rectal cancers. The efficacy of novel treatment strategies cannot be established without benchmarking the outcomes of dMMR rectal cancer with current therapy. We aimed to delineate the impact of dMMR on prognosis, the predicted response to fluoropyrimidine-based neoadjuvant therapy, and implications of germline alterations in the MMR genes in rectal cancer. METHODS Between 1992 and 2012, 62 patients with dMMR rectal cancers underwent multimodality therapy. Oncologic treatment and outcomes as well as clinical genetics work-up were examined. Overall and rectal cancer-specific survival were calculated by the Kaplan-Meier method. RESULTS The median age at diagnosis was 41 years. MMR deficiency was most commonly due to alterations in MSH2 (53%) or MSH6 (23%). After a median follow-up of 6.8 years, the 5-year rectal cancer-specific survival was 100% for stage I and II, 85.1% for stage III, and 60.0% for stage IV disease. Fluoropyrimidine-based neoadjuvant chemoradiation was associated with a complete pathologic response rate of 27.6%. The extent of surgical resection was influenced by synchronous colonic disease at presentation, tumor height, clinical stage, and pelvic radiation. An informed decision for a limited resection focusing on proctectomy did not compromise overall survival. Five of the 11 (45.5%) deaths during follow-up were due to extracolorectal malignancies. CONCLUSION dMMR rectal cancer had excellent prognosis and pathologic response with current multimodality therapy including an individualized surgical treatment plan. Identification of a dMMR rectal cancer should trigger germline testing, followed by lifelong surveillance for both colorectal and extracolorectal malignancies. We herein provide genotype-specific outcome benchmarks for comparison with novel interventions.

Oncological Outcomes after Robotic Proctectomy for Rectal Cancer: Analysis of a Prospective Database

Objective: The aim of this study is to evaluate the oncological outcomes of robotic total mesorectal excision (TME) at an NCI designated cancer center. Summary Background Data: The effectiveness of laparoscopic TME could not be established, but the robotic-assisted approach may hold some promise, with improved visualization and ergonomics for pelvic dissection. Oncological outcome data is presently lacking. Methods: Patients who underwent total mesorectal excision or tumor-specific mesorectal excision for rectal cancer between April 2009 and April 2016 via a robotic approach were identified from a prospective single-institution database. The circumferential resection margin (CRM), distal resection margin, and TME completeness rates were determined. Kaplan–Meier analysis of disease-free survival and overall survival was performed for all patients treated with curative intent. Results: A total of 276 patients underwent robotic proctectomy during the study period. Robotic surgery was performed initially by 1 surgeon with 3 additional surgeons progressively transitioning from open to robotic during the study period with annual increase in the total number of cases performed robotically. Seven patients had involved circumferential resection margins (2.5%), and there were no positive distal or proximal resection margins. One hundred eighty-six patients had TME quality assessed, and only 1 patient (0.5%) had an incomplete TME. Eighty-three patients were followed up for a minimum of 3 years, with a local recurrence rate of 2.4%, and a distant recurrence rate of 16.9%. Five-year disease-free survival on Kaplan–Meier analysis was 82%, and 5-year overall survival was 87%. Conclusions: Robotic proctectomy for rectal cancer can be performed with good short and medium term oncological outcomes in selected patients.

Implementation of a standardized electronic tool improves compliance, accuracy, and efficiency of trainee-to-trainee patient care handoffs after complex general surgical oncology procedures

Background. Duty‐hour regulations have increased the frequency of trainee‐trainee patient handoffs. Each handoff creates a potential source for communication errors that can lead to near‐miss and patient‐harm events. We investigated the utility, efficacy, and trainee experience associated with implementation of a novel, standardized, electronic handoff system. Methods. We conducted a prospective intervention study of trainee‐trainee handoffs of inpatients undergoing complex general surgical oncology procedures at a large tertiary institution. Preimplementation data were measured using trainee surveys and direct observation and by tracking delinquencies in charting. A standardized electronic handoff tool was created in a research electronic data capture (REDCap) database using the previously validated I‐PASS methodology (illness severity, patient summary, action list, situational awareness and contingency planning, and synthesis). Electronic handoff was augmented by direct communication via phone or face‐to‐face interaction for inpatients deemed “watcher” or “unstable.” Postimplementation handoff compliance, communication errors, and trainee work flow were measured and compared to preimplementation values using standard statistical analysis. Results. A total of 474 handoffs (203 preintervention and 271 postintervention) were observed over the study period; 86 handoffs involved patients admitted to the surgical intensive care unit, 344 patients admitted to the surgical stepdown unit, and 44 patients on the surgery ward. Implementation of the structured electronic tool resulted in an increase in trainee handoff compliance from 73% to 96% (P < .001) and decreased errors in communication by 50% (P = .044) while improving trainee efficiency and workflow. Conclusion. A standardized electronic tool augmented by direct communication for higher acuity patients can improve compliance, accuracy, and efficiency of handoff communication between surgery trainees.

Hyperfractionated Accelerated Reirradiation for Patients With Recurrent Anal Cancer Previously Treated With Definitive Chemoradiation

Objectives: Although chemoradiation is the standard of care for anal cancer, limited data exist regarding pelvic reirradiation (re-RT) for recurrent disease. We investigated toxicity and outcomes in patients who received prior pelvic radiation therapy (RT), and subsequently underwent hyperfractionated accelerated re-RT to the pelvis for recurrent anal cancer. Materials and Methods: We reviewed records of 10 patients with recurrent anal squamous cell carcinoma who previously received pelvic RT to at least 30 Gy as a component of their chemoradiation and underwent re-RT in 1.5 Gy twice daily fractions to the pelvis, with either preoperative (N=7) or definitive (N=3) intent. Results: The 3-year disease-free survival and 3-year overall survival rates were 40% and 60%. Four patients recurred within the reirradiated field, with a 3-year freedom from local progression rate of 56%. Of the 7 patients treated with preoperative intent, 5 proceeded to surgery, of whom 3 are alive and disease-free at a median duration of 43 months. Of the 3 patients treated definitively with no surgery, all are alive and disease-free at a median duration of 84 months. Re-RT resulted in one grade 3 acute toxicity and no grade 3 or higher late complications. Conclusions: Hyperfractionated accelerated re-RT was well-tolerated in patients with previously irradiated anal cancer. Patients treated with either definitive re-RT or re-RT followed by surgical resection had excellent rates of overall survival and freedom from local progression.

The role of surgery in the multidisciplinary management of patients with localized gastrointestinal stromal tumors

Surgical resection of localized gastrointestinal stromal tumors (GISTs) is associated with recurrence rates of approximately 50% at 5 years of follow-up. The introduction of tyrosine kinase inhibitors, such as imatinib, improved overall survival rates in advanced disease, while in the adjuvant setting, improved recurrence-free survival following resection of high-risk GIST. The demonstration of the clinical benefit of tyrosine kinase inhibitors in both the metastatic and adjuvant settings generated interest in neoadjuvant approaches for patients with operable locally advanced disease, particularly in difficult anatomic locations. The potential impact of tumor downsizing in areas such as the gastroesophageal junction, the duodenum or the rectum, on the extent of surgical resection and morbidity is real. The ongoing research regarding neoadjuvant therapy, the duration of adjuvant therapy and the optimal means by which to risk stratify patients with GIST continues to keep the treatment of this disease at the forefront of personalized cancer care.

Identification of preoperative factors associated with outcomes following surgical management of intra-abdominal recurrent or metastatic GIST following neoadjuvant tyrosine kinase inhibitor therapy

The role of surgical resection in the treatment of patients with metastatic/recurrent gastrointestinal stromal tumors (GIST) is unclear. The aim of this study was to identify preoperative factors associated with oncologic outcomes for recurrent/metastatic GIST after tyrosine kinase inhibitor (TKI) therapy.

Treatment of primary rectal adenocarcinoma after prior pelvic radiation: The role of hyperfractionated accelerated reirradiation

Purpose Previous studies have reported that hyperfractionated accelerated reirradiation can be used as part of multimodality treatment of locally recurrent rectal cancer with acceptable toxicity and promising outcomes. The purpose of this study was to evaluate the outcomes and toxicity of hyperfractionated accelerated reirradiation for patients with primary rectal adenocarcinoma and a history of prior pelvic radiation for other primary malignancies. Methods and materials We identified 10 patients with a prior history of pelvic radiation for other primary malignancies who were treated with hyperfractionated accelerated reirradiation for primary rectal adenocarcinoma. Radiation therapy was administered with 1.5 Gy twice daily fractions to a total dose of 39 Gy to 45Gy. Results The median follow-up time was 3.2 years (range, 0.6-9.0 years). Seven of 10 patients received surgery after reirradiation. The 3-year freedom-from-local-progression rate was 62% for all patients and 80% for patients who underwent surgery. The 3-year overall survival rate was 100%, with 3 deaths occurring at 4.7, 6.5, and 9.0 years after reirradiation. One patient had an acute Grade 3 toxicity of diarrhea, and 1 patient experienced a late Grade 3 toxicity of sacral insufficiency fracture. Conclusions Hyperfractionated accelerated reirradiation was well tolerated with promising rates of freedom from local progression and overall survival in patients with primary rectal cancer with a history of prior pelvic radiation therapy. This approach, along with concurrent chemotherapy and surgery, appears to be a viable treatment strategy for this patient population.