Matthew D. Callister

Reduced acute bowel toxicity in patients treated with intensity-modulated radiotherapy for rectal cancer.

PURPOSE We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. METHODS AND MATERIALS A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. RESULTS From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced ≥Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, ≥Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. CONCLUSIONS In the management of rectal cancer, IMRT is associated with a clinically significant reduction in lower GI toxicity compared with CRT. Further study is needed to evaluate differences in late toxicity and long-term efficacy.

Neoadjuvant chemoradiation compared to neoadjuvant radiation alone and surgery alone for Stage II and III soft tissue sarcoma of the extremities.

BackgroundNeoadjuvant chemoradiation (NCR) prior to resection of extremity soft tissue sarcoma (STS) has been studied, but data are limited. We present outcomes with NCR using a variety of chemotherapy regimens compared to neoadjuvant radiation without chemotherapy (NR) and surgery alone (SA).MethodsWe conducted a retrospective chart review of 112 cases.ResultsTreatments included SA (36 patients), NCR (39 patients), and NR (37 patients). NCR did not improve the rate of margin-negative resections over SA or NR. Loco-regional relapse-free survival, distant metastases-free survival, and overall survival (OS) were not different among the treatment groups. Patients with relapsed disease (OR 11.6; p = 0.01), and tumor size greater than 5 cm (OR 9.4; p = 0.01) were more likely to have a loco-regional recurrence on logistic regression analysis. Significantly increased OS was found among NCR-treated patients with tumors greater than 5 cm compared to SA (3 year OS 69 vs. 40%; p = 0.03). Wound complication rates were higher after NCR compared to SA (50 vs. 11%; p = 0.003) but not compared to NR (p = 0.36). Wet desquamation was the most common adverse event of NCR.ConclusionsNCR and NR are acceptable strategies for patients with STS. NCR is well-tolerated, but not clearly superior to NR.

Phase II Study of Preoperative Pemetrexed, Carboplatin, and Radiation Followed by Surgery for Locally Advanced Esophageal Cancer and Gastroesophageal Junction Tumors

Introduction: Based on favorable preliminary clinical data and the need to identify effective, well-tolerated neoadjuvant regimens for patients with locally advanced esophageal cancer, this clinical trial was undertaken. Methods: This phase II study tested 500 mg/m2 neoadjuvant pemetrexed intravenously and carboplatin with an area under the curve of 6 intravenously on days 1 and 22 in conjunction with concomitant radiation of 5040 centigray, which was given in 28 daily fractions of 180 centigray. The primary endpoint was the rate of pathologic complete response. Results: This trial closed early because, during an interim analysis, the primary endpoint fell short. However, 26 eligible patients were accrued. Twenty (74%) were men. Performance scores of 0, 1, and 2 were seen in 16 (59%), 9 (33%), and 2 (7%), respectively. Among eligible patients, 6 of 26 (23%; 95% confidence interval 9-44%) demonstrated a pathologic complete response. Twenty-two underwent a complete cancer resection. The median survival was 17.8 months (95% confidence interval: 12.2-30.7 months). In the neoadjuvant setting, 22 patients had at least one grade 3 or worse adverse event, and 8 patients had at least one grade 4 event. Postoperatively (within 30 days of surgery), there were three deaths, one grade 4 event (thrombosis), and three grade 3 events. Conclusions: The neoadjuvant regimen tested within this phase II trial demonstrated antineoplastic activity but fell short of yielding a complete pathologic response rate that merits further testing.

Extremity and Trunk Soft Tissue Sarcomas

Management of soft-tissue sarcomas of the extremities and trunk is optimally accomplished through a multidisciplinary team evaluation of each patient because of the diverse and complex nature of each clinical scenario. A team of orthopedic or surgical oncologists, radiation oncologists, medical oncologists, plastic surgeons, pathologists, and radiologists consider multiple issues including tumor stage, grade, location, and histologic type of tumor, as well as feasibility of a limb-sparing surgery, timing of radiation, and the patient’s performance status and comorbid illnesses. The rarity of these tumors in combination with the variety of presentation in extremity and truncal soft-tissue sarcomas limits the amount of prospective data available to reliably outline the management of all situations, and hence, there is a range of approaches utilized around the world today.

Isolated Supraclavicular Lymph Node Metastasis in Pancreatic Adenocarcinoma: A Report of Three Cases and Review of the Literature

CONTEXT Supraclavicular lymph nodes represent a rare site of metastasis in pancreatic cancer. We report three cases of pancreatic adenocarcinoma with metastases to supraclavicular lymph nodes. CASE REPORT A 51-year-old male was diagnosed with locally advanced pancreatic adenocarcinoma on computed tomography (CT) scan. He was recommended neoadjuvant chemotherapy followed by chemoradiation therapy. However, positron emission tomography (PET)/CT scans and subsequent fine needle aspiration cytology showed supraclavicular lymph node metastasis. The patient received systemic chemotherapy for metastatic pancreatic adenocarcinoma. The second patient, a 66-year-old female with pancreatic adenocarcinoma, underwent pancreaticoduodenectomy and was found to have peripancreatic lymph node involvement. She received adjuvant chemotherapy and was followed-up with surveillance CT scans, which did not reveal any metastasis. However, the patient complained of neck swelling. PET/CT scan and biopsy revealed supraclavicular lymph node metastasis from a pancreatic adenocarcinoma primary. The third patient, a 79-year-old male with a past history of thyroid carcinoma who was treated with partial thyroidectomy, developed neck swelling 4 years after his surgery. Fine needle aspiration cytology was consistent with known papillary thyroid carcinoma. Staging evaluations revealed a pancreatic mass for which he underwent subtotal pancreatectomy and splenectomy. Histopathology revealed grade 3 pancreatic adenocarcinoma. Excisional biopsy of a supraclavicular lymph node showed metastatic pancreatic adenocarcinoma. PET/CT results were consistent with these findings. CONCLUSION In patients with pancreatic adenocarcinoma, supraclavicular lymph node metastasis represents an uncommon, but clinically significant finding that can lead to changes in treatment planning. PET imaging represents a valuable tool in the detection and follow up of these patients.

Pemetrexed, Carboplatin, and Concomitant Radiation followed by Surgery for Locally Advanced Esophageal Cancer: Results of a Planned Interim Toxicity Analysis of North Central Cancer Treatment Group Study N044E.

Purpose This brief report describes a planned, interim, 6-patient toxicity analysis that confirms the safety of pemetrexed, carboplatin, radiation with subsequent surgery, as prescribed in the North Central Cancer Treatment Group trial N044E, in patients with locally advanced esophageal cancer. Methods Six patients with locally advanced, potentially resectable esophageal cancer received pemetrexed 500 mg/m2 and carboplatin AUC = 6 on days 1 and 22 with 5040 centigray of concomitant radiation in 28 fractions over 5.5 weeks followed by esophagectomy as a prelude to a phase II multi-institutional trial. Results Only 1 of the 6 patients experienced a grade 4 adverse event (neutropenia). This patient also experienced a grade 3 depression. Of the remaining 5 patients, three experienced at least one grade 3 adverse event (neutropenia, nausea/vomiting, and esophagitis). There were no deaths. Incidentally, one patient manifested a complete pathologic response, three a partial pathologic response, and one stable disease. Conclusion These preliminary observations on safety suggest that this regimen can be further studied in this clinical setting.

Cancers of the Colon, Rectum, and Anus

Patients with lower gastrointestinal cancer frequently require multidisciplinary management. Concurrent radiotherapy and chemotherapy is often used as an adjuvant to surgical resection in selected patients with resectable but high-risk rectal cancer. In patients with locally unresectable rectal and colon cancer, preoperative chemoradiation is preferably used as a component of the definitive procedure. For patients with anal cancer, concurrent chemoradiation has replaced abdominoperineal resection as the principal form of treatment. Appropriate radiotherapeutic management of the patient with lower gastrointestinal cancer includes proper patient selection and diagnostic evaluation, close cooperation by all physicians participating in the patient’s care, and the use of proper radiotherapeutic techniques. The introduction of intensity modulated radiation therapy (IMRT) into the treatment of both rectal and anal cancer provides the potential for reducing toxicity and improving tumor control with dose escalation.

Trimodality treatment for advanced esophageal cancer: Impact of minimally invasive esophagectomy.

125 Background: Esophageal cancer is best managed by multimodality therapy, frequently with chemotherapy (C) or chemo- radiotherapy (CRT) preceding resection. Minimally invasive esophagectomy (MIE) is increasingly accepted, but studies of MIE in advanced esophageal and gastroesophageal junction cancer after induction CRT are lacking. This report presents the data on MIE as part of tri-modality therapy for esophageal cancer at Mayo Clinic in Arizona (MCA). METHODS Patients (pts) who underwent CRT before or after MIE for cancer at MCA between November 2006 and May of 2010 were reviewed retrospectively. RESULTS 46 pts (40 males, and 6 females) met study criteria and were reviewed. Median age was 62 years (41-88 years). 45 pts (98%) had adenocarcinoma and one pt had squamous carcinoma. Initial clinical stage was IIA in 10 pts (22%), IIB in 3 pts (7%), III in 26 pts (55%), and IVA in 7 pts (15%) with positive celiac nodes. 43 pts (93%) underwent preoperative CRT with additional intra-operative radiotherapy in 4 pts. Median operating time was 354 min (range 211-567 min), median blood loss was 225 ml (range 50-1,400 ml), and median hospital stay was 8 days (range 5-48 days). 19 pts (41%), including the 3 who did not undergo preoperative CRT, received postoperative C or CRT due to either residual disease at resection or to local recurrence. 30 of 43 pts undergoing MIE after CRT were down staged (11 CR [25.6%], 10 near CR [23.3%]) demonstrating a major response to neoadjuvant therapy in 48.9% of pts. One pt died in hospital (from ARDS and sepsis subsequent to aspiration pneumonia) and two pts died within 30 days of surgery (one from pulmonary embolism, and the other from unknown causes) for a 30 day surgical mortality of 6.5%. 29 pts (63%) had a complication of surgery including 11 (24%) minor and 18 (39%) major complications. After a median follow-up of 13 months (range 0.9-43 months) 16 pts were diagnosed with recurrent disease and 10 of these pts have died of their disease. CONCLUSIONS CRT with MIE is associated with an acceptable morbidity and mortality level for pts with locally advanced esophageal cancer. These results compare favorably with morbidity, mortality, and recurrence rates in open esophagectomy pts. No significant financial relationships to disclose.