A phase II trial of gemcitabine and erlotinib followed by ChemoProton therapy plus capecitabine and oxaliplatin for locally advanced pancreatic cancer.

Background: Epidermal growth factor receptor (EGFR) is overexpressed in pancreatic cancer. EGFR expression plays a potentially important role in modulation of tumor sensitivity to either chemotherapy or radiotherapy. Erlotinib is a receptor tyrosine kinase inhibitor with specificity for EGFR/HER1. A phase II trial was conducted to explore the efficacy of a regimen utilizing erlotinib and proton therapy. Methods: Patients with unresectable or borderline resectable non-metastatic adenocarcinoma of the pancreas were included. Patients received 8-week systemic treatment with gemcitabine 1,000 mg/m2 and erlotinib 100 mg (GE). If there was no evidence of metastatic disease after GE, then patients preceded with proton therapy to 50.4 Gy in 28 fractions with concurrent capecitabine 825 mg/m2 (CPT). This was followed with oxaliplatin 130 mg/m2 and capecitabine 1,000 mg/m2 (CapOx) for 4 cycles. The primary study objective was 1-year overall survival (OS). The benchmark was 43% 1-year survival as demonstrated in RTOG/NRG 98-12. The Kaplan-Meier method was used to estimate the one-year OS and the median OS and progression-free survival (PFS). Results: The study enrolled 9 patients ages 47-81 years old (median 62) between January 2013 and March 2016, when the trial was closed due to low patient accrual. The 1-year OS rate was 55.6% (95% CI: 31% to 99%). The median OS was 14.1 months (95% CI: 11.4-NE) and the median PFS was 10.8 months (95% CI: 7.44-NE). A majority of patients completed CPT and GE, but only 33.3% completed the four cycles of CapOx. A third of patients experienced grade 3 toxicities, which were all hepatic along with one patient who also had grade 3 diarrhea. There were no grade 4 or 5 toxicities. Four patients were enrolled with borderline resectable disease, three of which were eligible for pancreaticoduodenectomy after GE and CPT treatment. One of two patients who underwent resection had a negative margin. Conclusions: This regimen for locally advanced pancreatic cancer (LAPC) exceeded the pre-specified benchmark and was safe and well tolerated. Additional investigations utilizing more current systemic treatment regimens with proton therapy are warranted. Trial Registration: ClinicalTrials.gov identifier (NCTNCT01683422).

Factors associated with the refusal of surgery and the associated impact on survival in patients with rectal cancer using the National Cancer Database.

BACKGROUND: Surgical resection is an integral component of the curative-intent treatment for most patients with non-metastatic rectal cancer. However, some patients refuse surgery for a number of reasons. Utilizing the National Cancer Database (NCDB), we investigated the sociodemographic and clinical factors associated with patients who were coded as having been offered but refused surgery, and the factors affecting overall survival (OS) in these patients. METHODS: Adult patients with adenocarcinoma of the rectum (excluding T1N0M0 and M1 disease) diagnosed from 2004 to 2015 were analyzed in this retrospective cohort study. Logistic regression was performed to identify factors associated with refusal of surgery. OS of patients refusing surgery was compared using Kaplan-Meier estimate, log-rank test, propensity score matching, and proportional hazards regression. RESULTS: A total of 55,704 patients were identified: 54,266 received definitive surgery (97.4%) and 1,438 refused (2.6%). Of patients refusing surgery, 135 (9.4%) were stage I, 709 (49.3%) were stage II, and 594 (41.3%) were stage III. Patients were more likely to refuse surgery as the study period progressed (P<0.01). Factors associated with refusal of surgery on multivariate analysis include: age ≥70 years, Black race, non-private insurance, and tumor size greater than 2 cm (all values P≤0.01). The 5-year OS was 61.6% for the surgery cohort and 35.7% for the refusal cohort. In the propensity matched groups, median survival was 84.2 months in patients who received definitive surgery compared to 43.7 months in patients who refused surgery. As an index for comparison, patients who refused surgery but received both radiotherapy and chemotherapy had a median survival of 48.5 months. Among patients that refused surgery, those that received radiotherapy alone, chemotherapy alone, or radiotherapy and chemotherapy (compared to no treatment) experienced a survival benefit (all values P≤0.01). CONCLUSIONS: In patients with non-metastatic adenocarcinoma of the rectum reported in the NCDB, age, race, and insurance status were associated with refusal of surgery. Refusal of surgery was more common in the later years of the study. Survival is poor in patients who refused surgical resection.

Proton stereotactic body radiation therapy for liver metastases-results of 5-year experience for 81 hepatic lesions.

BACKGROUND: To report on our institutional experience using Proton stereotactic body radiation therapy (SBRT) for patients with liver metastases. METHODS: All patients with liver metastases treated with Proton SBRT between September 2012 and December 2017 were retrospectively analyzed. Local control (LC) and overall survival (OS) were estimated using the Kaplan-Meier method calculated from the time of completion of Proton SBRT. LC was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1). Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. RESULTS: Forty-six patients with 81 lesions were treated with Proton SBRT. The median age was 65.5 years old (range, 33-86 years) and the median follow up was 15 months (range, 1-54 months). The median size of the gross tumor volume (GTV) was 2.5 cm (range, 0.7-8.9 cm). Two or more lesions were treated in 56.5% of patients, with one patient receiving treatment to a total of five lesions. There were 37 lesions treated with a biologically effective dose (BED) ≤60, 9 lesions with a BED of 61-80, 22 lesions with a BED of 81-100, and 13 lesions with a BED >100. The 1-year and 2-year LC for all lesions was 92.5% (95% CI, 82.7% to 96.8%). The grade 1 and grade 2 toxicity rates were 37% and 6.5%, respectively. There were no grade 3 or higher toxicities and no cases of radiation-induced liver disease (RILD). CONCLUSIONS: Proton SBRT for the treatment of liver metastases has promising LC rates with the ability to safely treat multiple liver metastases. Accrual continues for our phase II trial treating liver metastases with Proton SBRT to 60 GyE (Gray equivalent) in 3 fractions.

Troubleshooting Sentinel Lymph Node Biopsy in Breast Cancer Surgery.

BACKGROUND: Performing a sentinel lymph node biopsy (SLNB) is the standard of care for axillary nodal staging in patients with invasive breast cancer and clinically negative nodes. The procedure provides valuable staging information with few complications when performed by experienced surgeons. However, variation in proficiency exists for this procedure, and a great amount of experience is required to master the technique, especially when faced with challenging cases. The purpose of this paper was to provide a troubleshooting guide for commonly encountered technical difficulties in SLNB, and offer potential solutions so that surgeons can improve their own technical performance from the collective knowledge of experienced specialists in the field. METHODS: Information was obtained from a convenience sample of six experienced breast cancer specialists, each actively involved in training surgeons and residents/fellows in SLNB. Each surgeon responded to a structured interview in order to provide salient points of the SLNB procedure. RESULTS: Four of the key opinion surgical specialists provided their perspective using technetium-99 m sulfur colloid, and two shared their experience using blue dye only. Distinct categories of commonly encountered problem scenarios were presented and agreed upon by the panel of surgeons. The responses to each of these scenarios were collected and organized into a troubleshooting guide. DISCUSSION: We present a compilation of 'tips' organized as a troubleshooting guide to be used to guide surgeons of varying levels of experience when encountering technical difficulties with SLNB.