Sagar A. Patel

Proton therapy for breast cancer after mastectomy: early outcomes of a prospective clinical trial.

PURPOSE Dosimetric planning studies have described potential benefits for the use of proton radiation therapy (RT) for locally advanced breast cancer. We report acute toxicities and feasibility of proton delivery for 12 women treated with postmastectomy proton radiation with or without reconstruction. METHODS AND MATERIALS Twelve patients were enrolled in an institutional review board-approved prospective clinical trial. The patients were assessed for skin toxicity, fatigue, and radiation pneumonitis during treatment and at 4 and 8 weeks after the completion of therapy. All patients consented to have photographs taken for documentation of skin toxicity. RESULTS Eleven of 12 patients had left-sided breast cancer. One patient was treated for right-sided breast cancer with bilateral implants. Five women had permanent implants at the time of RT, and 7 did not have immediate reconstruction. All patients completed proton RT to a dose of 50.4 Gy (relative biological effectiveness [RBE]) to the chest wall and 45 to 50.4 Gy (RBE) to the regional lymphatics. No photon or electron component was used. The maximum skin toxicity during radiation was grade 2, according to the Common Terminology Criteria for Adverse Events (CTCAE). The maximum CTCAE fatigue was grade 3. There have been no cases of RT pneumonitis to date. CONCLUSIONS Proton RT for postmastectomy RT is feasible and well tolerated. This treatment may be warranted for selected patients with unfavorable cardiac anatomy, immediate reconstruction, or both that otherwise limits optimal RT delivery using standard methods.

Early stage rectal cancer: clinical and pathologic prognostic markers of time to local recurrence and overall survival after resection

BACKGROUND: Resection without adjuvant therapy results in a low recurrence rate for patients with stage I (T1/2 N0) rectal cancer in the range of 4% to 16% at 5 years. There are limited data, however, regarding clinical or pathologic prognostic markers for recurrence in this population. OBJECTIVE: The aim of this study is to assess the clinical and pathologic factors associated with local recurrence and overall survival in patients with early-stage rectal cancer after resection. DESIGN: This is a retrospective study. SETTING: This study was conducted at 2 tertiary care centers in Boston, Massachusetts. PATIENTS: From 2000 to 2008, 175 patients with stage I rectal cancer treated with local or total mesorectal excision without adjuvant therapy were identified. MAIN OUTCOME MEASURES: Time to local recurrence after resection and overall survival were evaluated for all patients with complete follow-up data. Perioperative data were reviewed to identify staging method, preoperative CEA, type of surgery, tumor size, number of lymph nodes resected, histological grade, circumferential resection margin, perineural invasion, lymphovascular invasion, and tumor ulceration. Data were analyzed by using a Cox proportional hazards regression model. RESULTS: Of the eligible cohort, 137 patients had complete follow-up data for analysis of time to local recurrence, and only 23 (16.8%) patients had local recurrence. Among these 23 patients, the median time to recurrence was 1.1 years (0.1–7.8). On multivariate analysis, male sex, current alcohol use, and tumor ulceration were associated with heightened risk of local recurrence. Of the original cohort, 173 patients had complete follow-up for overall survival analysis. Among these patients, the median overall survival was 12 years. On multivariable analysis, age at diagnosis >65 years and T2 pathologic stage were associated with decreased survival. LIMITATIONS: As in any retrospective study, there is a potential for selection bias. Several patients were excluded from the analysis due to inadequate follow-up data. These results from two academic medical centers with specialized colorectal surgeons may not be generally applicable. The relatively small number of events, ie, recurrences, suggest the findings should be validated in a larger study. CONCLUSIONS: For patients with stage I rectal cancer treated with resection alone, these results provide important prognostic information and may help identify those who could benefit from additional therapy.

Rapid vascular glucose uptake via enzyme-assisted subcutaneous infusion: enzyme-assisted subcutaneous infusion access study.

BACKGROUND Enzyme-assisted subcutaneous infusion (EASI), with subcutaneous human recombinant hyaluronidase pretreatment, may offer an alternative to standard intravenous (IV) access. OBJECTIVES This studys objectives were to assess paramedic (Emergency Medical Technician-Paramedic [EMTP])-placed EASI access in volunteers to determine (1) feasibility of EMTP EASI access placement; (2) subject/EMTP ratings of placement ease, discomfort, and overall EASI vs IV preference; and (3) speed of intravascular uptake of EASI infusate. METHODS Twenty adults underwent 20-gauge IV placement by 4 EMTPs, receiving a 250-mL maximal-rate IV bolus of normal saline. Next, each subject received in the other arm a 20-gauge EASI access line (with 1-mL injection of 150 U of human recombinant hyaluronidase), through which was infused 250 mL D5NS (1 g glucose was labeled with stable tracer 13C). Blood draws enabled gas chromatography/mass spectrometry (GC/MS) assessment of 13C-glucose uptake. Intravenous access and EASI access were compared for time parameters and subject/EMTP ratings. Data were analyzed with median and interquartile range, Kruskal-Wallis testing, Fisher exact test, and regression (GC/MS data). RESULTS Intravenous access and EASI access were successful in all 20 subjects. Compared with EASI access (all placed in <15 seconds), IV access took longer; but the 250-mL bolus was given more quickly via IV access. EMTPs rated EASI easier to place than IV; pain ratings were similar for IV and EASI. The GC/MS showed intravascular uptake at all time points. CONCLUSIONS Enzyme-assisted subcutaneous infusion is faster and easier to initiate than IV access; intravascular absorption of EASI-administered fluids begins within minutes.

Postmastectomy radiation therapy technique and cardiopulmonary sparing: A dosimetric comparative analysis between photons and protons with free breathing versus deep inspiration breath hold

PURPOSE Dosimetric studies have suggested greater cardiopulmonary sparing with protons over photons for left-sided postmastectomy radiation therapy (PMRT). Modern techniques such as deep inspiration breath hold (DIBH) can help spare the heart. This analysis compares photon and proton delivery with and without DIBH. METHODS AND MATERIALS Ten women with left breast cancer referred for PMRT on a prospective clinical trial with unfavorable cardiac anatomy underwent free breathing (FB) and DIBH computed tomography simulation. A partially wide tangent photon (PWTF) during DIBH, passively scattered proton during FB, pencil-beam scanning (PBS) proton during FB, and PBS proton during DIBH plan was completed for each patient. Plans were designed to achieve 95% prescription dose coverage to 95% of chest wall and regional lymphatics while maximally sparing heart and lungs. RESULTS All techniques resulted in similar target coverage, although protons improved homogeneity indices and cardiopulmonary sparing (omnibus P < .0001 for each metric). Heart/lung metrics for PWTF with DIBH, scattered protons with FB, PBS protons with FB, and PBS protons with DIBH, respectively, were as follows: mean heart dose (2.09, 0.39, 0.98, 0.71 Gy relative biological effectiveness [RBE]), mean left ventricle dose (3.72, 0.08, 0.19, 0.21 GyRBE), V20 left ventricle (2.73, 0.03, 0, 0%), maximum left anterior descending artery dose (46.14, 8.28, 4.58, 4.63 GyRBE), mean lung dose (13.30, 5.74, 7.63, 7.49 GyRBE), and V20 lung (26.04, 12.04, 15.18, 14.43 %). Pairwise testing confirmed an improvement in each metric with all proton plans compared with PWTF with DIBH; there were no differences in homogeneity indices or cardiopulmonary sparing between passively scattered and PBS protons, regardless of addition of DIBH. CONCLUSIONS For left-sided PMRT, passively scattered or PBS protons with or without DIBH improves homogeneity and cardiopulmonary sparing without compromise in target coverage compared with PWTF photons with DIBH. Furthermore, the addition of DIBH to proton therapy did not provide a significant dosimetric benefit.

Impact of total radiotherapy dose on survival for head and neck Merkel cell carcinoma after resection

Head and neck Merkel cell carcinoma (MCC) is commonly treated with surgery and adjuvant radiotherapy (RT) for high‐risk features. The optimal radiation dose is unknown.

Identifying an Optimal Adjuvant Radiotherapy Dose for Extremity and Trunk Merkel Cell Carcinoma Following Resection: An Analysis of the National Cancer Database

Importance Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine neoplasm with a high risk of recurrence following resection. Despite a rising incidence over the past 3 decades, there is a paucity of prospective data owing to the rarity of this disease. Objective To determine the optimal adjuvant radiation therapy (RT) dose following resection of localized MCC of the extremities or trunk. Design, Setting, and Participants Using the National Cancer Database, a large national database consisting of a heterogeneous population and treatment settings, we retrospectively analyzed a cohort of 2093 patients 18 years or older with stage I to III MCC of the extremities and/or trunk treated with definitive surgery and adjuvant RT between 1998 and 2011. Exclusion criteria included receiving treatment with palliative intent, preoperative RT, non–external-beam RT, and radiation dose of 30 Gy or lower or 70 Gy or higher. Cox proportional hazards regression model was used to compare overall survival (OS) between RT dose groups, accounting for age, sex, race, stage, surgery type, margin status, comorbidities, and use of chemotherapy. Exposures Radiation therapy dose was categorized into 4 groups: group 1 received the lowest dose (>30 to <40 Gy); group 2, the next lowest (40 to <50 Gy); group 3, the second highest dose (50 to 55 Gy); and group 4, the highest dose (>55 to 70 Gy). Main Outcome and Measure Overall survival. Results Data from 2093 patients were analyzed; there were 1293 men (61.8%) and 800 women (38.2%) (median age, 73 years). After a median follow-up of 37 months for the entire cohort, 904 deaths were reported. The 3-year OS rates for groups 1, 2, 3, and 4 were 41.8%, 69%, 69.2%, and 66%, respectively (omnibus P < .001). Compared with group 3 (50 to 55 Gy), equivalent OS was seen in group 2 (40 to <50 Gy; adjusted hazard ratio [AHR], 0.89; 95% CI, 0.63-1.27; P = .52) and group 4 (>55 to 70 Gy; AHR, 1.18; 95% CI, 0.93-1.48; P = .17), but worse OS was found in group 1 (>30 to <40 Gy; AHR, 2.63; 95% CI, 1.44-4.80; P < .001). Conclusions and Relevance Adjuvant RT dose from 40 to lower than 50 Gy appears adequate for extremities and/or trunk stage I to III MCC, with OS equivalent to that found at higher-dose regimens (>50 to 70 Gy).

Combined Modality Therapy for Rectal Cancer.

The primary therapy for any potentially curative rectal cancer is surgery. For locally advanced tumors (i.e., T3-4 and/or node positive), the very high rate of local and distant recurrences has necessitated a standard adjuvant regimen of preoperative chemoradiation and postoperative chemotherapy. Several controversies regarding this approach remain, including the technique and fractionation scheme of radiation therapy prior to surgery, the choice of concomitant chemotherapy, and whether all patients require postoperative systemic therapy. Furthermore, in an era of improving staging imaging and surgical techniques, an opportunity for de-escalation of therapy to improve patient morbidity and quality of life may arise. At the same time, advances in radiation and systemic therapy may help facilitate less invasive, sphincter-preserving surgery. This review addresses these questions and others that remain areas of active clinical investigation.

Cost–Effectiveness of Surveillance for Distant Recurrence in Extremity Soft Tissue Sarcoma

BackgroundOptimal distant recurrence (DR) surveillance strategies for extremity soft tissue sarcoma (STS) are unknown. We performed a cost–effectiveness analysis of different imaging modalities performed at guideline-specified intervals.MethodsWe developed a Markov model simulating lifetime outcomes for 54-year-old patients after definitive treatment for American Joint Committee on Cancer stage II-III extremity STS using four surveillance strategies: watchful waiting (WW), chest X-ray (CXR), chest computed tomography (CCT), and positron emission tomography–computed tomography (PET/CT). Probabilities, utilities, and costs were extracted from the literature and Medicare claims to determine incremental cost–effectiveness ratios (ICER).ResultsCCT was the most effective and most costly strategy with CXR the most cost–effective strategy at a societal willing-to-pay (WTP) of

An Enlarging Neck Mass

100,000/quality-adjusted life year (QALY). The ICER was

Role of Radiation Therapy for Intrahepatic Cholangiocarcinoma

12,113/QALY for CXR versus