Edward A. Levine

Cytoreductive Surgery Combined With Perioperative Intraperitoneal Chemotherapy for the Management of Peritoneal Carcinomatosis From Colorectal Cancer: A Multi-Institutional Study

PURPOSE The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. PATIENTS AND METHODS A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. RESULTS The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. CONCLUSION The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.

Oxaliplatin Combined With Weekly Bolus Fluorouracil and Leucovorin As Surgical Adjuvant Chemotherapy for Stage II and III Colon Cancer: Results From NSABP C-07

PURPOSE This phase III clinical trial evaluated the impact on disease-free survival (DFS) of adding oxaliplatin to bolus weekly fluorouracil (FU) combined with leucovorin as surgical adjuvant therapy for stage II and III colon cancer. PATIENTS AND METHODS Patients who had undergone a potentially curative resection were randomly assigned to either FU 500 mg/m2 intravenous (IV) bolus weekly for 6 weeks plus leucovorin 500 mg/m2 IV weekly for 6 weeks during each 8-week cycle for three cycles (FULV), or the same FULV regimen with oxaliplatin 85 mg/m2 IV administered on weeks 1, 3, and 5 of each 8-week cycle for three cycles (FLOX). RESULTS A total of 2,407 patients (96.6%) of the 2,492 patients randomly assigned were eligible. Median follow-up for patients still alive is 42.5 months. The hazard ratio (FLOX v FULV) is 0.80 (95% CI, 0.69 to 0.93), a 20% risk reduction in favor of FLOX (P < .004). The 3- and 4-year disease-free survival (DFS) rates were 71.8% and 67.0% for FULV and 76.1% and 73.2% for FLOX, respectively. Grade 3 neurosensory toxicity was noted in 8.2% of patients receiving FLOX and in 0.7% of those receiving FULV (P < .001). Hospitalization for diarrhea associated with bowel wall thickening occurred in 5.5% of the patients receiving FLOX and in 3.0% of the patients receiving FULV (P < .01). A total of 1.2% of patients died as a result of any cause within 60 days of receiving chemotherapy, with no significant difference between regimens. CONCLUSION The addition of oxaliplatin to weekly FULV significantly improved DFS in patients with stage II and III colon cancer. FLOX can be recommended as an effective option in clinical practice.

Early- and Long-Term Outcome Data of Patients With Pseudomyxoma Peritonei From Appendiceal Origin Treated by a Strategy of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

PURPOSE Pseudomyxoma peritonei (PMP) originating from an appendiceal mucinous neoplasm remains a biologically heterogeneous disease. The purpose of our study was to evaluate outcome and long-term survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an international registry study. PATIENTS AND METHODS A retrospective multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group International. RESULTS Two thousand two hundred ninety-eight patients from 16 specialized units underwent CRS for PMP. Treatment-related mortality was 2% and major operative complications occurred in 24% of patients. The median survival rate was 196 months (16.3 years) and the median progression-free survival rate was 98 months (8.2 years), with 10- and 15-year survival rates of 63% and 59%, respectively. Multivariate analysis identified prior chemotherapy treatment (P < .001), peritoneal mucinous carcinomatosis (PMCA) histopathologic subtype (P < .001), major postoperative complications (P = .008), high peritoneal cancer index (P = .013), debulking surgery (completeness of cytoreduction [CCR], 2 or 3; P < .001), and not using HIPEC (P = .030) as independent predictors for a poorer progression-free survival. Older age (P = .006), major postoperative complications (P < .001), debulking surgery (CCR 2 or 3; P < .001), prior chemotherapy treatment (P = .001), and PMCA histopathologic subtype (P < .001) were independent predictors of a poorer overall survival. CONCLUSION The combined modality strategy for PMP may be performed safely with acceptable morbidity and mortality in a specialized unit setting with 63% of patients surviving beyond 10 years. Minimizing nondefinitive operative and systemic chemotherapy treatments before definitive cytoreduction may facilitate the feasibility and improve the outcome of this therapy to achieve long-term survival. Optimal cytoreduction achieves the best outcomes.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: A consensus statement

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin : a consensus statement

Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemotherapy With Mitomycin C for Peritoneal Carcinomatosis from Nonappendiceal Colorectal Carcinoma

Background: Cytoreductive surgery (CS) and intraperitoneal hyperthermic chemotherapy (IPHC) are efficacious in patients with disseminated mucinous tumors of the appendix. We reviewed our experience using this approach for nonappendiceal colorectal cancer (NACC).Methods: We performed a retrospective chart review of a prospective database for patients undergoing CS and IPHC with mitomycin C for peritoneal carcinomatosis from colorectal primary lesions between December 1991 and April 2002.Results: There were 77 patients, with a median age of 54 years. Peritoneal carcinomatosis was synchronous and metachronous in 27% and 73% patients, respectively. Seventy-five percent of patients (n = 58) had received chemotherapy prior to IPHC. Complete resection of all gross disease was accomplished in 37 patients (48%). The mean carcinoembryonic antigen level decreased from a preoperative value of 31.2 to a postoperative value of 6.9 (P < .0001). Overall survival (OS) at 1, 3, and 5 years was 56%, 25%, and 17%, respectively. With a median follow-up of 15 months, the median OS was 16 months. Perioperative morbidity and mortality were 30% and 12%, respectively. Hematologic toxicity occurred in 15 patients (19%). Cox regression analysis identified poor performance status (P = .018), bowel obstruction (P = .001), malignant ascites (P = .001), and incomplete resection of gross disease (P = .011) as independent predictors of decreased survival. Patients with complete resection of all gross disease had a 5-year OS of 34%, with a median OS of 28 months.Conclusions: CS and IPHC with mitomycin C can improve outcomes for select patients with peritoneal spread from NACC. One third of patients who undergo complete resection of gross disease have long-term survival.

Pseudomyxoma peritonei of appendiceal origin: a clinicopathologic analysis of 101 patients uniformly treated at a single institution, with literature review.

Pseudomyxoma peritonei is a clinical term for gelatinous ascites, usually secondary to an appendiceal tumor. The pathologic classification of pseudomyxoma peritonei and its associated appendiceal tumors has been plagued with controversy and confusing terminology. In an effort to clarify this, we reviewed the pathology of 101 patients, all treated at our institution from 1993 to 2005, with pseudomyxoma peritonei of appendiceal origin. All patients were uniformly treated with our standardized protocol. This is the largest pathologic series solely devoted to appendiceal neoplasia with gelatinous ascites.The cases were assigned, according to previously published criteria, to the categories of disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), or PMCA with intermediate (well differentiated) features (PMCA-I), with the exception that any case with a signet-ring cell component was considered as PMCA and not PMCA-I. By histologic category, 58 patients had DPAM, 23 were PMCA, and 20 were PMCA-I.One-year, 3-year, and 5-year survival outcomes were not significantly different between DPAM and PMCA-I. DPAM and PMCA-I also exhibited a roughly equal incidence of parenchymal (beyond the serosa) organ invasion. Survival outcomes were significantly worse for PMCA, compared with PMCA-I and DPAM. After reviewing our data and the literature, mucinous carcinoma peritonei-low grade was applied to the low-grade histology of pseudomyxoma peritonei, including those cases referred to by some as DPAM in the same category as PMCA-I. Cases that are moderately differentiated to poorly differentiated are classified as mucinous carcinoma peritonei-high grade.

High-Resolution Fluorodeoxyglucose Positron Emission Tomography with Compression (“Positron Emission Mammography”) is Highly Accurate in Depicting Primary Breast Cancer

Abstract:  We sought to prospectively assess the diagnostic performance of a high‐resolution positron emission tomography (PET) scanner using mild breast compression (positron emission mammography [PEM]). Data were collected on concomitant medical conditions to assess potential confounding factors. At four centers, 94 consecutive women with known breast cancer or suspicious breast lesions received 18F‐fluorodeoxyglucose (FDG) intravenously, followed by PEM scans. Readers were provided clinical histories and x‐ray mammograms (when available). After excluding inevaluable cases and two cases of lymphoma, PEM readings were correlated with histopathology for 92 lesions in 77 women: 77 index lesions (42 malignant), 3 ipsilateral lesions (3 malignant), and 12 contralateral lesions (3 malignant). Of 48 cancers, 16 (33%) were clinically evident; 11 (23%) were ductal carcinoma in situ (DCIS), and 37 (77%) were invasive (30 ductal, 4 lobular, and 3 mixed; median size 21 mm). PEM depicted 10 of 11 (91%) DCIS and 33 of 37 (89%) invasive cancers. PEM was positive in 1 of 2 T1a tumors, 4 of 6 T1b tumors, 7 of 7 T1c tumors, and 4 of 4 cases where tumor size was not available (e.g., no surgical follow‐up). PEM sensitivity for detecting cancer was 90%, specificity 86%, positive predictive value (PPV) 88%, negative predictive value (NPV) 88%, accuracy 88%, and area under the receiver‐operating characteristic curve (Az) 0.918. In three patients, cancer foci were identified only on PEM, significantly changing patient management. Excluding eight diabetic subjects and eight subjects whose lesions were characterized as clearly benign with conventional imaging, PEM sensitivity was 91%, specificity 93%, PPV 95%, NPV 88%, accuracy 92%, and Az 0.949 when interpreted with mammographic and clinical findings. FDG PEM has high diagnostic accuracy for breast lesions, including DCIS. 

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement. Society of Surgical Oncology.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin : a consensus statement

Restorative yoga for women with breast cancer: findings from a randomized pilot study.

Objectives: Restorative yoga (RY) is a gentle type of yoga that may be beneficial for cancer patients and post‐treatment survivors. Study goals were: to determine the feasibility of implementing a RY intervention for women with breast cancer; and to examine group differences in self‐reported emotional, health‐related quality of life, and symptom outcomes.

Predictive value of 18-fluoro-deoxy-glucose-positron emission tomography (18F-FDG-PET) in the identification of responders to chemoradiation therapy for the treatment of locally advanced esophageal cancer.

Objective:To evaluate the utility of 18F-FDG-PET in predicting response to concomitant chemoradiation in locally-advanced esophageal cancer. Summary Background Data:Approximately 25% of esophageal cancer patients experience a pathologic complete response (pCR) to preoperative chemoradiation therapy. Computed tomography, endoscopy, and endoscopic ultrasound are unable to identify patients experiencing a pCR. Growing evidence supports the use of 18F-FDG-PET in the staging of esophageal cancer in its ability to detect occult metastatic and lymph nodal disease. The identification of patients with a pCR to chemoradiation could potentially spare those patients the morbidity associated with a resection. Methods:Eligibility criteria included T3-T4N0M0 or T1-T4N1M0 esophageal cancer. Patients underwent an initial 18F-FDG-PET before treatment and then repeated 4 to 6 weeks after chemoradiation, prior to the esophagectomy. Chemoradiation consisted of: cisplatinum, 5-fluorouracil, and radiation to a median dose of 50.4 Gy. Pathologic response was determined from a systematic review of the esophagectomy specimens. Results:Sixty-four patients have completed therapy to date. Response was as follows: pCR 27%, pathologic residual microscopic (pCRmicro) 14.5%, partial response 19%, and stable or progressive disease 39.5%. A pretreatment standardized uptake value (SUVmax1hour) ≥15 was associated with an observed 77.8% significant response (pCR + pCRmicro) compared with 24.2% for patients with a pretreatment SUVmax1hour <15 (P = 0.005). Significant response was observed in 71.4% of patients with a decrease in SUVmax1hour ≥10 compared with 33.3% when the SUVmax1hour decreased <10 (P = 0.004). Conclusions:Pretreatment and posttreatment 18F-FDG-PET can be useful for predicting significant response to chemoradiation in esophageal cancer. These data should be considered in evaluation of patients for esophagectomy after chemoradiation.