Showing papers by "Prajnan Das published in 2019"

Esophageal and Esophagogastric Junction Cancers, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

Abstract: Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Squamous cell carcinoma is the most common histology in Eastern Europe and Asia, and adenocarcinoma is most common in North America and Western Europe. Surgery is a major component of treatment of locally advanced resectable esophageal and esophagogastric junction (EGJ) cancer, and randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival. Targeted therapies including trastuzumab, ramucirumab, and pembrolizumab have produced encouraging results in the treatment of patients with advanced or metastatic disease. Multidisciplinary team management is essential for all patients with esophageal and EGJ cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on recommendations for the management of locally advanced and metastatic adenocarcinoma of the esophagus and EGJ.

Laparoscopic Hyperthermic Intraperitoneal Chemotherapy is Safe for Patients with Peritoneal Metastases from Gastric Cancer and May Lead to Gastrectomy.

Abstract: Laparoscopic hyperthermic intraperitoneal chemotherapy (LS-HIPEC) is a novel strategy for patients with gastric adenocarcinoma (GA) metastatic to the peritoneum. We evaluated the safety profile of LS-HIPEC for patients with positive peritoneal cytology (PPC) or carcinomatosis from GA. Outcomes were reviewed of patients with stage IV GA with peritoneal involvement who received LS-HIPEC from June 2014 to January 2017. LS-HIPEC included a 60-minute perfusion of mitomycin-C (30 mg) and cisplatin (200 mg) with inflow temperatures of 41–42 °C and outflow temperatures of 39–40 °C. A total of 71 LS-HIPEC procedures were performed in 44 patients. At diagnosis, 68% (n = 30) had carcinomatosis and 32% (n = 14) had isolated PPC. Three patients (7%) underwent LS-HIPEC for intractable ascites. All patients initially received systemic chemotherapy, and 20 patients (45%) received pre-procedural chemoradiotherapy. The median number of LS-HIPEC procedures performed per patient was one (range 1–5 procedures). There were no conversions to laparotomy, two outflow catheter obstructions, and one major (Clavien-Dindo grade III) surgical complication within 30 days. A total of seven postoperative adverse hematologic events (> CTCAE 2) were observed in five patients (11%), without any major renal or gastrointestinal adverse events within 30 days. The median overall length of hospital stay after LS-HIPEC was 2 (range 2–11) days. Eleven patients (25%) underwent secondary gastrectomy following resolution of peritoneal cytology. Laparoscopic HIPEC is a safe procedure and may be repeated in patients with peritoneal metastases from gastric cancer. Future studies are required to determine the optimal HIPEC regimen and timing relative to systemic therapy to best minimize morbidity.

Characteristics and Survival of Gastric Cancer Patients with Pathologic Complete Response to Preoperative Therapy.

Abstract: Pathologic complete response of a primary tumor (ypT0) after preoperative therapy is associated with improved overall survival (OS). However, whether other variables are associated with outcome for gastric cancer patients with ypT0 status is unknown. This study reviewed an institutional database of patients who underwent resection of gastric or gastroesophageal adenocarcinoma after preoperative therapy and identified patients with ypT0 status. Cox regression models were used to identify clinicopathologic predictors of OS. Of 77 patients with ypT0 status identified in this study, 36 (47%) had gastroesophageal junction tumors. At presentation, 62 patients (81%) had clinical T3 disease, and 7 (9%) had clinical T4 disease. The clinical nodal status was positive (cN+) for 45 patients (58%). Preoperative chemoradiation was administered to 75 patients (97%). The median follow-up duration was 3.54 years. The median OS was 10 years, and the 5-year OS rate was 61%. Univariable analysis identified age of 65 years or older at the time of diagnosis, histologic grade, and ypN status as significant predictors of OS. Multivariable analysis confirmed age of 65 years or older [hazard ratio (HR), 4.26; p < 0.001] and persistent nodal disease (ypN+ status; HR, 5.12; p < 0.001) to be independently associated with OS. Clinical stage was not associated with survival. In the subset of ypT0N0 patients, no clinicopathologic feature was predictive of survival. For gastric or gastroesophageal adenocarcinoma patients with ypT0 status after preoperative therapy, ypN+ status substantially reduced survival. Pretreatment clinical stage had no impact on OS for patients with a pathologic complete response.

Yield of peritoneal cytology in staging patients with gastric and gastroesophageal cancer

Abstract: Background Guidelines for gastric and gastroesophageal (GE) cancer recommend staging laparoscopy (SL) with peritoneal cytology (PC). However, the reliability of PC is unknown. The primary purpose of this study was to determine the sensitivity of PC. Methods We analyzed a prospectively maintained database of patients who underwent SL and PC for gastric and GE cancer. Test sensitivity of PC for detecting peritoneal disease was assessed. Survival analyses were used to examine the implication of PC. Results There were 1186 patients that underwent SL and PC; 282 (24%) were found with carcinomatosis. PC was analyzed in 214 (76%) of these patients and 77 (36%) were found to have no malignant cells. In this setting, PC had a sensitivity of 64% for confirming peritoneal disease. Those with peritoneal disease had a poorer 5-year overall survival (5.8% vs 37.7%; P .05). Conclusions PC has limited sensitivity for detecting peritoneal disease. Positive PC alone carries a similar poor survival as in patients with gross carcinomatosis. Improvements in the identification of microscopic disease in peritoneal washings are needed.

National Cancer Institute (NCI) state of the science: Targeted radiosensitizers in colorectal cancer.

Abstract: Colorectal cancer (CRC) represents a major public health problem as the second leading cause of cancer-related mortality in the United States. Of an estimated 140,000 newly diagnosed CRC cases in 2018, roughly one-third of these patients will have a primary tumor located in the distal large bowel or rectum. The current standard-of-care approach includes curative-intent surgery, often after preoperative (neoadjuvant) radiotherapy (RT), to increase rates of tumor down-staging, clinical and pathologic response, as well as improving surgical resection quality. However, despite advancements in surgical techniques, as well as sharpened precision of dosimetry offered by contemporary RT delivery platforms, the oncology community continues to face challenges related to disease relapse. Ongoing investigations are aimed at testing novel radiosensitizing agents and treatments that might exploit the systemic antitumor effects of RT using immunotherapies. If successful, these treatments may usher in a new curative paradigm for rectal cancers, such that surgical interventions may be avoided. Importantly, this disease offers an opportunity to correlate matched paired biopsies, radiographic response, and molecular mechanisms of treatment sensitivity and resistance with clinical outcomes. Herein, the authors highlight the available evidence from preclinical models and early-phase studies, with an emphasis on promising developmental therapeutics undergoing prospective validation in larger scale clinical trials. This review by the National Cancer Institute's Radiation Research Program Colorectal Cancer Working Group provides an updated, comprehensive examination of the continuously evolving state of the science regarding radiosensitizer drug development in the curative treatment of CRC.

Computed tomography-based biomarker outcomes in a prospective trial of preoperative FOLFIRINOX and chemoradiation for borderline resectable pancreatic cancer

Abstract: PURPOSEEffective preoperative regimens and biomarkers for pancreatic ductal adenocarcinoma (PDAC) are lacking. We prospectively evaluated fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLF...

Executive Summary of the American Radium Society Appropriate Use Criteria for Local Excision in Rectal Cancer

Abstract: The goal of treatment for early stage rectal cancer is to optimize oncologic outcome while minimizing effect of treatment on quality of life. The standard of care treatment for most early rectal cancers is radical surgery alone. Given the morbidity associated with radical surgery, local excision for early rectal cancers has been explored as an alternative approach associated with lower rates of morbidity. The American Radium Society Appropriate Use Criteria presented in this manuscript are evidence-based guidelines for the use of local excision in early stage rectal cancer that include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) used by a multidisciplinary expert panel to rate the appropriateness of imaging and treatment procedures. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. These guidelines are intended for the use of all practitioners and patients who desire information regarding the use of local excision in rectal cancer.

Assessment of setup uncertainty in hypofractionated liver radiation therapy with a breath-hold technique using automatic image registration–based image guidance

Abstract: Target localization in radiation therapy is affected by numerous sources of uncertainty. Despite measures to minimize the breathing motion, the treatment of hypofractionated liver radiation therapy is further challenged by residual uncertainty coming from involuntary organ motion and daily changes in the shape and location of abdominal organs. To address the residual uncertainty, clinics implement image-guided radiation therapy at varying levels of soft-tissue contrast. This study utilized the treatment records from the patients that have received hypofractionated liver radiation therapy using in-room computed tomography (CT) imaging to assess the setup uncertainty and to estimate the appropriate planning treatment volume (PTV) margins in the absence of in-room CT imaging. We collected 917 pre-treatment daily in-room CT images from 69 patients who received hypofractionated radiation therapy to the liver with the inspiration breath-hold technique. For each treatment, the daily CT was initially aligned to the planning CT based on the shape of the liver automatically using a CT-CT alignment software. After the initial alignment, manual shift corrections were determined by visual inspection of the two images, and the corrections were applied to shift the patient to the physician-approved treatment position. Considering the final alignment as the gold-standard setup, systematic and random uncertainties in the automatic alignment were quantified, and the uncertainties were used to calculate the PTV margins. The median discrepancy between the final and automatic alignment was 1.1 mm (0–24.3 mm), and 38% of treated fractions required manual corrections of ≥3 mm. The systematic uncertainty was 1.5 mm in the anterior-posterior (AP) direction, 1.1 mm in the left-right (LR) direction, and 2.4 mm in the superior-inferior (SI) direction. The random uncertainty was 2.2 mm in the AP, 1.9 mm in the LR, and 2.2 mm in the SI direction. The PTV margins recommended to be used in the absence of in-room CT imaging were 5.3 mm in the AP, 3.5 mm in the LR, and 5.1 mm in the SI direction. Manual shift correction based on soft-tissue alignment is substantial in the treatment of the abdominal region. In-room CT can reduce PTV margin by up to 5 mm, which may be especially beneficial for dose escalation and normal tissue sparing in hypofractionated liver radiation therapy.

Executive Summary of the American Radium Society Appropriate Use Criteria for Treatment of Anal Cancer.

Abstract: Purpose The American Radium Society Appropriate Use Criteria (ARS AUC) presented in this manuscript are evidence-based guidelines for curative- intent treatment of non-metastatic anal squamous cell cancer that are developed by a multidisciplinary expert panel. Methods Guideline development and systematic review using PRISMA methodology include an extensive analysis of current medical literature from peer-reviewed journals and application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. In those instances where evidence is not definitive, expert opinion may be used to recommend imaging or treatment. Results Evidence-based guidelines are presented about the evaluation and treatment of anal cancer in various clinical scenarios that are derived from supporting literature and multidisciplinary consensus. Conclusions These guidelines are intended for the use of all practitioners and patients who desire information about the management of anal cancer covered in these guidelines.

The effect of IMRT on acute toxicity in patients with gastric cancer treated with preoperative chemoradiation.

Abstract: 153Background: Two trials are currently investigating preoperative chemoradiation (CRT) for localized gastric adenocarcinoma. However, radiation therapy (RT) can be associated with relatively high ...

Improving quality through A.I.: Applying machine learning to predict unplanned hospitalizations after radiation.

Abstract: 271Background: Unplanned hospitalizations may diminish quality of care among cancer patients receiving radiotherapy (RT). In patients undergoing RT for gastrointestinal (GI) cancers, we hypothesize...

Anal Cancer: Toxicities and Management

Abstract: Definitive chemoradiation has been established as the primary, curative treatment option for patients with anal cancer. Chemoradiation has been shown to be highly effective in this disease; however, it is associated with acute and late toxicities. Toxicities associated with the standard chemotherapy agents (5-fluorouracil [5-FU] and mitomycin C) include diarrhea, nausea, stomatitis, mucositis, hand-foot syndrome, and myelosuppression. Acute toxicities from radiotherapy include dermatitis, diarrhea, tenesmus, nausea, hematologic toxicity, anorectal pain, fatigue, and urinary dysfunction. Long-term toxicities from radiotherapy include pelvic bone insufficiency; anorectal, gastrointestinal, and sexual dysfunction; and chronic skin changes. Intensity-modulated radiation therapy (IMRT) may mitigate the risk of acute toxicities; however, long-term gastrointestinal and sexual toxicities remain a concern. Appropriate management of acute and chronic toxicities is a critical part of the clinical care of patients with anal cancer.