Melvyn Goldberg

Complete Response to Neoadjuvant Chemoradiotherapy in Esophageal Carcinoma Is Associated With Significantly Improved Survival

PURPOSE Attempts to improve survival of patients with esophageal cancer have been made using induction chemoradiotherapy (CRT) followed by surgery. A large single-center experience was reviewed to determine which treatment-related variables could predict survival and recurrence. PATIENTS AND METHODS All patients undergoing esophagectomy between January 1994 and December 2002 were reviewed. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method. RESULTS Of 171 patients with invasive cancer, 131 (77%) underwent preoperative CRT. The average age was 60 years, and most patients were male (85%). Operations performed included Ivor-Lewis (60%), transhiatal (8%), three-hole (23%), or left thoracoabdominal (8%) esophagectomy. Perioperative mortality rate was 5%. Median overall survival (OS) of the entire group was 33 months, and the 5-year OS rate was 26%. Induction CRT was associated with a 33% 5-year survival rate compared with 11% for surgery alone (P = .43). Patients downstaged to pathologic stage 0 or I had an improved OS and disease-free survival (DFS) compared with those patients who were not downstaged (P = .022). Additionally, the ability to perform an R0 resection was a significant factor for OS and DFS (n = 130; P < .0001 and P <.0002, respectively). CONCLUSION Response to CRT and the ability to perform an R0 resection are associated with significantly improved survival in patients with esophageal carcinoma.

Induction chemotherapy with mitomycin, vindesine, and cisplatin for stage III unresectable non-small-cell lung cancer: results of the Toronto Phase II Trial.

PURPOSE The 5-year survival rates with surgical resection for preoperatively identified stage IIIA N2 non-small-cell lung cancer (NSCLC) are less than 10%. A pilot study of mitomycin, vindesine, and cisplatin (MVP) induction chemotherapy was undertaken in an attempt to improve the curative potential of surgery in this group of patients. PATIENTS AND METHODS Thirty-nine patients with mediastinoscopy stage IIIA N2 NSCLC received two cycles of MVP. Responding patients underwent thoracotomy for resection and two further courses of MVP. RESULTS The overall response rate was 64% (25 of 39) with three complete and 22 partial responses. Twenty-two patients were resected, which included a radical mediastinal node dissection. Eighteen resections were complete and four were incomplete. Pathologically, three patients (7.7%) had no tumor remaining. Toxicity included two postoperative deaths secondary to a bronchopleural (BP) fistula, mitomycin pulmonary toxicity in two patients, and septic deaths in four patients. Twenty-eight patients have died; 20 have recurrent or progressive disease. Eight of the 18 patients completely resected have recurred, with a median time to recurrence of 20.6 months. Sites of recurrence include two locoregional, five distant (two in brain), and one in both. Median survival of all 39 patients is 18.6 months, with a 3-year survival of 26%. The median survival for those patients completely resected was 29.7 months with a 3-year survival of 40%. CONCLUSIONS We conclude (1) that MVP is an effective but toxic chemotherapeutic regimen for limited NSCLC; (2) the median survival seems to be prolonged; and (3) the role of induction chemotherapy followed by surgery in stage IIIA N2 NSCLC requires a phase III randomized trial to compare it with other treatment modalities.

Correlates of tobacco use among smokers and recent quitters diagnosed with cancer

Smoking after a cancer diagnosis shortens survival time, increases risk of recurrence and the development of another primary tumor, reduces treatment efficacy, and increases treatment complications. Nevertheless, many patients who smoked prior to their illness continue to smoke after diagnosis and treatment. The development of effective smoking cessation interventions for cancer patients has been slowed by the lack of data concerning psychological correlates of smoking in this population. This study, with 74 cancer patients, showed that smoking and lower readiness to quit was associated with: having relatives at home who smoke, a longer time between diagnosis and assessment, completion of medical treatment, greater nicotine dependence, lower self-efficacy, quitting pros, and risk perceptions, and higher quitting cons, fatalistic beliefs, and emotional distress. Thus, smoking cessation treatments for cancer patients should include pharmacotherapy, relapse prevention, and counseling designed to facilitate self-efficacy, quitting pros, and risk awareness and to reduce the quitting cons, fatalism, and distress.

Longitudinal predictors of continued tobacco use among patients diagnosed with cancer

Even though continued smoking by cancer patients adversely affects survival and quality of life, about one third of patients who smoked prior to their diagnosis continue to smoke after their diagnosis. The implementation of smoking cessation treatments for cancer patients has been slowed by the lack of data on correlates of tobacco use in this population. Thus, this longitudinal study assessed demographic, medical, addiction, and psychological predictors of tobacco use among 74 head, neck, and lung cancer patients. Multivariable binary logistic regression analyses, with outcome categorized as smoker or nonsmoker, indicated that the likelihoodthat patients would be a smoker was associated with lower levels of perceived risk and a higher level of quitting cons. Multivariable nominal logistic regression, with outcome classified as continuous smoker, continuous quitter, relapser, or follow-up quitter, indicated that: (a) patients categorized as continuous smokers reported significantly lower quitting self-efficacy than follow-up quitters and continuous quitters, (b) relapsers reported a significantly lower level of quitting self-efficacy than either follow-up quitters or continuous quitters, and (c) continuous smokers exhibited a significantly lower level of risk perceptions than continuous abstainers. These findings can be useful for the development and evaluation of treatments to promote smoking cessation among cancer patients.

Pleural Cytologies in Lung Cancer Without Pleural Effusions

BACKGROUND Malignant pleural effusions significantly increase the stage of lung cancer with attendant worsening of prognosis. There is a paucity of literature evaluating malignant pleural lavage cytology in patients without pleural effusions. We propose to determine the incidence of malignant pleural cytologies in patients without pleural effusions who undergo curative resection for lung cancer and to identify any predictive risk factors for positive cytology. METHODS Seventy-eight patients underwent curative resection for lung cancer. Lavage was performed before lung manipulation and after resection and cytologically evaluated. RESULTS Twelve pneumonectomies, 64 lobectomies, and 2 wedge resections were performed on 40 men and 38 women with an average age of 65.7 years. Fourteen percent had positive lavage cytology before lung resection with an 11% (6 of 53) incidence in stage I. A significant correlation to adenocarcinoma compared with squamous cell was found (p = 0.03) but not to stage, T or N status, grade, pleural invasion, or preoperative transthoracic needle biopsy. CONCLUSIONS The incidence of positive pleural cytology in otherwise stage I patients is disconcertingly high. Positive cytology may be a prognosticator of a more aggressive tumor biology.

Comparing cancer patients who enroll in a smoking cessation program at a comprehensive cancer center with those who decline enrollment

Despite the availability of smoking interventions for cancer patients, many eligible patients decline enrollment into such programs. We examined reasons patients provide for declining smoking treatment and compared treatment decliners to enrollees.

Induction Cisplatin and Paclitaxel Followed by Combination Chemoradiotherapy with 5-Fluorouracil, Cisplatin, and Paclitaxel Before Resection in Localized Esophageal Cancer: A Phase II Report

BackgroundMultimodality therapy for esophageal cancer holds promise for improving outcome in this lethal disease. On the basis of encouraging data from a phase I trial, we conducted a phase II study of preoperative chemotherapy, followed by concurrent chemoradiotherapy and surgery.MethodsPatients with clinically staged resectable esophageal cancer were treated with induction cisplatin and paclitaxel, followed by 45 Gy of external beam radiation with concurrent infusional 5-fluorouracil and weekly cisplatin and paclitaxel. Four to eight weeks after multimodality induction, esophagectomy was performed in suitable patients. Study end points were survival, pathologic complete response, and toxicity.ResultsTwenty-one patients were enrolled with a median age of 58 years, and all patients were clinically staged II or III. Sixteen (76.2%) patients completed the trial, of whom four (25%) had a pathologic complete response. One patient died from postoperative complications. Grade 3 or 4 toxicity was observed in 76% of patients, and dose-limiting toxicity was seen in 6 of the first 14 patients, thus necessitating a planned dose reduction of paclitaxel. At a median follow-up of 30 months, 13 patients remain alive. The 2-year disease-specific survival for the study population was 78%.ConclusionsThis regimen of multimodality therapy before resection resulted in an encouraging 2-year survival rate but a disappointing rate of pathologic complete response and was toxic, necessitating a predetermined paclitaxel dose reduction. The incorporation of taxanes into induction strategies for esophageal cancer seems promising, but the optimal schedule remains undefined.

A Phase II Study of Concurrent Carboplatin and Paclitaxel and Thoracic Radiotherapy for Completely Resected Stage II and IIIA Non-small Cell Lung Cancer

Background: To determine the feasibility of combining concurrent carboplatin/paclitaxel and thoracic radiotherapy (TRT) for completely resected stage II and IIIA non-small cell lung cancer. Methods: Eligibility stipulated gross total resections with involved lymph nodes (N1 or N2), pathologic stage II or IIIA non-small cell lung cancer. TRT consisted of 50.4 Gy in 28 fractions with a boost of 10.8 Gy for extranodal extension (ENE) or 16.2 Gy for involved surgical margins. Chemotherapy was administered every 3 weeks: carboplatin (area under the curve of 5) and paclitaxel (175 mg/m2) during TRT for two cycles, with doses increased to an area under the curve of 7.5 and 225 mg/m2, respectively, for two cycles after TRT. Cox multivariate regression analysis was used to confirm independent predictors of outcome among clinical and treatment-related factors: age, T stage, N stage, presence of ENE, presence of involved surgical margins, histopathology. Results: Between April 1997 and March 2001, 42 patients were enrolled. Two patients were deemed ineligible due to having T4 disease, leaving 40 patients for analysis. Ninety-two percent (37/40) of patients had T1 or T2 disease; 60% (24/40) had N2 disease. Nine patients (22.5%) had ENE and 15% (six patients) had involved surgical margins. At a median follow up of 37 months (range, 3–103; median, 68 months for living patients), the 2- and 5-year Kaplan–Meier estimates of local regional control, freedom from distant metastasis, freedom from brain metastasis, and overall survival were 92% and 88%, 77% and 59%, 87% and 71% and 72% and 44%, respectively. Fourteen patients developed distant metastasis as the initial site of failure, eight of whom had brain metastasis. Brain metastasis was the only site of failure in four of the eight patients. Multivariate regression analysis demonstrated that the only independent predictor of overall survival was histology (p = 0.02). Patients with adenocarcinoma had a 5-year overall survival of 28% versus 68% for all other cell types. There were no independent predictors of distant metastases or brain metastases on multivariate regression analysis. Treatment was tolerated reasonably well: 92% of patients (37/40) received the planned doses of TRT; 67% of patients (27/40) received all four cycles of chemotherapy. Five patients developed grade 3 esophagitis, and three patients experienced grade 3 pneumonitis. Two patients experienced grade 5 toxicity. One was treatment related due to a patient who developed grade 3 esophagitis who developed an aspiration pneumonia that progressed to acute respiratory distress syndrome. Conclusions: Our results support the Radiation Therapy Oncology Group 97-05 findings and suggest that with new and better tolerated chemotherapy regimens the strategy of concurrent TRT and chemotherapy after completely resected stage II and IIIA non-small cell lung cancer should be further explored.

Multimodality therapy for resectable cancer of the thoracic esophagus.

The frequency of esophageal carcinoma continues to increase in North America primarily because of the increased incidence of Barretts epithelium in the distal esophagus and its malignant potential. Aggressive treatments involving multimodality therapies have been offered to improve overall poor survival rates. A review of this experience follows, to explain the rationale and to compare results of therapies. Although preoperative chemoradiation therapy is commonly used for locally advanced disease, few data support its superiority over surgical resection alone, followed by adjuvant therapy when appropriate. Hence this regimen should be limited to patients enrolled in controlled, randomized studies until the data support its widespread use.

Survival following intensive preoperative combined modality therapy with paclitaxel, cisplatin, 5-fluorouracil, and radiation in resectable esophageal carcinoma: A phase I report

PURPOSE To assess the benefits of aggressive chemoradiation therapy followed by surgery in resectable esophageal carcinoma. METHOD Twenty-nine patients with resectable carcinoma were treated with 60 Gy of radiation (2 Gy daily for 6 weeks) and concurrent chemotherapy consisting of continuous infusion of 5-fluorouracil (200-225 mg/m(2)/d), paclitaxel (25, 40, 50, or 60 mg/m(2)) weekly over 1 hour, and cisplatin (25 mg/m(2)) weekly immediately following paclitaxel throughout radiation. Patients received either 4 cycles of postoperative paclitaxel 175 mg/m(2) over 3 hours and cisplatin 75 mg/m(2) every 3 weeks or paclitaxel 175 mg/m(2) over 3 hours and cisplatin 75 mg/m(2) every 3 weeks prior to the initiation of chemoradiation. After induction therapy and restaging, esophagectomy was performed 4 to 6 weeks later. RESULTS Twenty-seven patients were eligible for study (26 men, 23 with adenocarcinoma). Median age was 58 years (range 30-73). The maximum tolerated dose combination was paclitaxel 50 mg/m(2) over 1 hour weekly, cisplatin 25 mg/m(2) over 1 hour weekly, 5-fluorouracil 200 mg/m(2)/d by continuous infusion throughout radiotherapy and radiation to 60 Gy. Twenty-two patients completed therapy and underwent surgical resection. Four patients had complete pathological responses and 18 had partial responses with no mortality. The commonest dose-limiting toxicity was mucositis and esophagitis (n = 7). Median follow-up of 27 patients was 150 weeks (range 7-303). At 2-year follow-up 16/27 (59%) were alive and 15/27 (56%) were free of disease. At 4-year follow-up 12/27 (44%) were alive and free of disease. Median follow-up of 22 patients undergoing esophagectomy was 205 weeks (range 26-303). At 4-year follow-up 10/22 (45%) were alive and free of disease. For the 18 patients treated at or above the maximum tolerated dose, median follow-up was 151 weeks (range 35-206) and at 3-year follow-up 9/18 (50%) were alive and free of disease. CONCLUSION Aggressive combined modality therapy of esophageal carcinoma was associated with excellent long-term survival in this phase I trial.