Neoadjuvant chemoradiotherapy for esophageal cancer: is it worthwhile?

BACKGROUND: With promising results from several institutions, many centers began treating patients with esophageal cancer with neoadjuvant chemoradiotherapy (NC) followed by esophagectomy. This approach is demanding for the patient and has not been proved to be better than esophagectomy alone. OBJECTIVE: To assess survival time and measures of quality of life associated with NC. DESIGN: A retrospective review during 1990 to 1996. SETTING: The 3 tertiary academic hospitals affiliated with the University of Massachusetts Medical School, Worcester. PARTICIPANTS: All patients (N=51) with cancer of the middle or lower esophagus who were treated with NC followed by esophagectomy during this period. MAIN OUTCOME MEASURES: Median and 1-, 2-, and 3-year survival times; median preoperative treatment time (first office visit for surgical consultation before beginning NC to the date of surgery), median hospital stay, and postoperative swallowing function. RESULTS: The median survival time of all patients was 16.3 months; 1-, 2-, and 3-year overall survival rates were 67%, 46%, and 39%, respectively. The median hospital stay was 12 days. The median postoperative treatment time was 3.3 months, which was 20% of the median survival time. Of the 51 patients, 19 were alive with a median follow-up time of 2.5 years. Twenty-nine percent of the patients had a complete pathological response with median and 1-, 2-, and 3-year survival rates of 17.5 months, 73%, 57%, and 57%, respectively. Palliation of dysphagia was excellent, with 44 (93%) of 47 operative survivors taking either a soft diet (18 [38%]) or a regular (26 [55%]) diet by the first postoperative visit. CONCLUSIONS: Median survival time with NC followed by esophagectomy for resectable cancer of the esophagus does not appear to be significantly better than that reported for esophagectomy alone. Further, treatment time with NC consumed 20% of survival time. Examining only these outcome variables suggests that NC is not worth-while. However, examining a longer-term outcome survival variable, such as 3-year survival time, suggests that NC followed by esophagectomy may result in greater long-term survival than that reported for esophagectomy alone. We conclude that further randomized, controlled studies are necessary before NC followed by esophagectomy is considered superior to esophagectomy alone for the treatment of resectable esophageal cancer.     

Combined chemotherapy and radiotherapy, followed or not by surgery, in squamous cell carcinoma of the esophagus

BACKGROUND: This study was designed to evaluate the feasibility of a neo-adjuvant combined chemo-radiotherapy in patients with localized squamous cell carcinoma of the esophagus. PATIENTS AND METHODS: Forty-two patients with squamous cell carcinoma of the esophagus, stages II and III (or stage I if considered to be poor candidates for immediate curative surgery), age less than 70 years and WHO performance status 0 to 2, were enrolled in a study of radiotherapy combined with chemotherapy, consisting of 2 (operated patients) or 3 (nonoperated patients) courses of cisplatin, vindesine, mitomycin-C or cisplatin, vinblastine. Surgery was routinely proposed to patients. RESULTS: Thirty-seven patients (88%) received full preoperative therapy. Of 30 patients responding to this preoperative therapy, 12 had a third cycle of treatment and 15 had esophagectomy. Three of the operated patients had no pathological evidence of residual tumour. Median survival of all 42 patients is 11 months and the 2-year survival rate is 29%. There is no difference in survival among responding operated or non-operated patients. Our group represents 95% of all eligible cases of squamous cell carcinoma of the esophagus occurring in Geneva during the study period. CONCLUSION: Our series gives a realistic view of the median survival of a population of patients eligible for neo-adjuvant therapy of esophagus cancer, and suggests that secondary surgery might not improve the patient survival. Furthermore, non-selected patients are at high risk for therapy-related death.     

Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer

BACKGROUND: We performed a multi-institutional randomized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer. METHODS: Preoperative chemotherapy for patients randomly assigned to the chemotherapy group included three cycles of cisplatin and fluorouracil. Surgery was performed two to four weeks after the completion of the third cycle; patients also received two additional cycles of chemotherapy after the operation. Patients randomly assigned to the immediate-surgery group underwent the same surgical procedure. The main end point was overall survival. RESULTS: Of the 440 eligible patients with adequate data , 213 were assigned to receive preoperative chemotherapy and 227 to undergo immediate surgery. After a median possible study time of 55.4 months, there were no significant differences between the two groups in median survival: 14.9 months for the patients who received preoperative chemotherapy and 16.1 months for those who underwent immediate surgery (P=0.53). At one year, the survival rate was 59 percent for those who received chemotherapy and 60 percent for those who had surgery alone; at two years, survival was 35 percent and 37 percent, respectively. The toxic effects of chemotherapy were tolerable, and the addition of chemotherapy did not appear to increase the morbidity or mortality associated with surgery. There were no differences in survival between patients with squamous-cell carcinoma and those with adenocarcinoma. Weight loss was a significant predictor of poor outcome (P=0.03). With the addition of chemotherapy, there was no change in the rate of recurrence at locoregional or distant sites. CONCLUSIONS: Preoperative chemotherapy with a combination of cisplatin and fluorouracil did not improve overall survival among patients with epidermoid cancer or adenocarcinoma of the esophagus.     

Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small-cell lung cancer: mature results of a phase II trial

The ability of rats to learn the location of a hidden platform in a swim maze was compared in animals with excitotoxic lesions of the anterior or posterior (retrosplenial) cingulate cortex or radiofrequency lesions of the cingulum bundle or fimbria-fornix. Performance of this allocentric spatial task was unaffected by the posterior cingulate cortex lesions, while anterior cingulate cortex damage produced only a mild acquisition deficit. Transection of the fornix and lesions of the cingulum bundle produced similar patterns of impairment on initial acquisition, but the cingulum bundle lesions had less effect on reversal of the task. The results from the water maze, and from a subsequent T-maze alternation task, indicate that cingulum bundle lesions can produce a spatial deficit that is similar, but milder, to that observed after fornix transection. The results of the excitotoxic lesions suggest that previous studies examining conventional cingulate lesions may have been influenced by damage to adjacent fibre tracts, such as the cingulum bundle.     

Combined lung resection for advanced thoracic esophageal carcinoma

We performed lung resection together with esophagectomy in 2 patients with advanced thoracic esophageal cancer. Both patients survived more than 2 years with no evidence of disease. The first case was a 60-year-old man who had a cancer lesion in middle of the intra-thoracic esophagus (Im) and the right lower lobe of the lung was involved. In March 1989, right lower lobectomy of the lung was performed with esophagectomy. Pathologic examination showed well differentiated squamous cell carcinoma invading the lung parenchyma and intrapulmonary lymph node. Postoperatively, 44 Gy of radiation and Peplomycin cancer chemotherapy was performed. The patient survived 51 months after surgery and died of chronic myelogenous leukemia. The second case was a 60-year-old man who underwent thoracic esophagectomy with resection of the involved pericardium and right lung in February 1992. Pathologic examination showed N3 lymph node metastasis. Postoperatively, the patient received 48 Gy of radiation and was free from cancer after 30 months. In conclusion, better surgical results are expected in cases of advanced thoracic esophageal cancer with lung involvement which can be completely resected en bloc with the primary tumor even in a3 cases than in those with aortic or tracheobronchial involvement.     

Use of concurrent chemotherapy, accelerated fractionation radiation, and surgery for patients with esophageal carcinoma

BACKGROUND: The results of a Phase II study of concurrent chemotherapy and accelerated fractionation radiation therapy followed by surgical resection for patients with both adenocarcinoma and squamous cell carcinoma of the esophagus are presented. Pretreatment and postinduction staging were correlated with pathologic findings at surgery to assess the role of surgical resection and the predictive value of noninvasive staging techniques. METHODS: Patients received 2 induction courses with 4-day continuous intravenous infusions of cisplatin (20 mg/m2/day) and 5-fluorouracil (1000 mg/m2/day) beginning on Day 1 and Day 21, concurrent with a split course of accelerated fractionation radiation (1.5 grays [Gy] twice daily, to a total dose of 45 Gy). All patients were subsequently referred for surgical resection. A single, identical postoperative course of chemotherapy and 24 Gy accelerated fractionation radiation was planned for patients with residual tumor at surgery. RESULTS: Seventy-four patients were entered on this study; 72 patients were considered eligible and evaluable. Induction toxicity included nausea (85%), increased dysphagia (90%), neutropenia (<1000/mm3) (43%), thrombocytopenia (<20,000/mm3) (10%), and reversible nephrotoxicity (8%). Sixty-seven patients (93%) underwent surgery, and 65 (90%) were found to have resectable tumors. Twelve of these patients (18%) died perioperatively, and 18 (27%) had no residual pathologic evidence of disease. Resolution of symptoms and normalization of radiographic studies, endoscopy, or esophageal ultrasound did not identify pathologic complete responders accurately. No patient completing induction therapy and surgery experienced a locoregional recurrence. The Kaplan-Meier 4-year projected recurrence free and overall survival rates were 49% and 44%, respectively. CONCLUSIONS: Although this regimen is feasible, there was significant preoperative toxicity and perioperative mortality. Nonetheless, the recurrence free and overall survival rates were encouraging. However, no staging tool can predict a pathologic complete response after induction therapy accurately, suggesting a continued need for surgical resection.     

食管癌后程三维适形放疗的临床疗效评价

Objective:The aim of our study was to evaluate the clinical results and acute side effects of late course three-dimensional conformal radiotherapy (3DCRT) for esophageal carcinoma.Methods:From January 2004 to October 2006,70 patients with esophageal carcinoma received late course 3DCRT.Their clinical data were analyzed retrospectively.The short-term clinical results,acute side effects,local control rates and survival rates were evaluated.Results:The complete response rate was 62.9%,partial response rate was 35.7%,and the overall response rate was 98.6%.The 1-,2- and 3-year local control rates were 77.1%,51.4% and 45.7%,respectively.The 1-,2- and 3-year overall survival rates were 75.7%,54.3% and 38.6%,respectively.The median survival time was 26 months.Conclusion:The technique of late course 3DCRT is an effective treatment for esophageal carcinoma and tend to improve the overall survival rate.     

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission

PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.     

The use of the aortic bypass in the surgery of the esophageal carcinoma invading the thoracic aorta

During the period from 1980 to 1989, five patients with carcinoma of the esophagus invading the thoracic aorta were treated by resection of the involved aortic segment combined with esophagectomy. Various types of arterial bypass were applied in order to provide blood flow to the distal aorta during aortic clamping. These included one permanent aorto-aortic bypass, two axillo-femoral bypass and one subclavian-aortic bypass. There was one death within 30 days and one developed paresis. These arterial bypasses are beneficial to esophageal surgery because it is technically easy and it does not necessitate systemic heparinization which maybe associated with profuse bleeding.     

食管癌全程三维适形放疗后程加速超分割的疗效观察

Objective:The aim of the study was to evaluate the therapeutic effect and safety of whole-course three-dimen-sional conformal radiotherapy (3DCRT) combined with late-course accelerated hyperfractionated radiotherapy (LCAFR) on patients with esophageal carcinoma.Methods:one hundred and one patients with esophageal carcinoma were divided into two groups.Observing group (49 cases) were treated by whole-course 3DCRT.Patients in control group (52 cases) were treated by conventional radiotherapy.Clinical efficiencies and radiation toxicities were compared between two groups.Re-sults:The side effects including radiation esophagitis (63.2%) and tracheitis (49.0%) decreased in observing group,but there was no significant difference between two groups (69.2% and 55.7% in controls).The 1-,2- and 3-year tumor local control rates and overall survival rates in the observing group were significantly improved compared with the control group,being respectively 87.8%,75.5%,63.3% vs 71.2%,55.8%,42.3% and 85.7%,71.4%,46.7% vs 69.2%,51.9%,26.9% (all P < 0.05).Conclusion:The therapeutic effect of whole-course 3DCRT combined with LCAFR for esophageal carcinomas is superior to conventional radiotherapy.     

Thyroid carcinoma after high-dose external radiotherapy for Hodgkin's disease: report of three cases

Three patients (two female and one male), who had received mantle irradiation for Hodgkin's disease eight, ten, and twelve years previously, developed papillary thyroid carcinoma. The radiation doses to the necks overlying the site of thyroid cancers were 3000, 4000, and 4100 rads, respectively. It has been stated that there is no risk of developing thyroid cancer with such high doses of external irradiation but apparently this complication will be encountered in a small number of patients.     

Intraoperative radiotherapy for pancreatic carcinoma with hepatic or peritoneal metastases

BACKGROUND/AIMS: The purpose of this study was to determine the efficacy of intraoperative radiotherapy (IORT) for unresectable pancreatic carcinoma associated with hepatic or peritoneal metastasis. METHODOLOGY: Between 1991 and 1994, 53 patients with pancreatic carcinoma associated with hepatic or peritoneal metastasis underwent surgery. Twenty-four of these patients received IORT, while 29 received no radiation therapy. The efficacy of IORT on the postoperative survival and pain relief for these patients was retrospectively analyzed. RESULTS: Postoperative survival was lowest in the subgroup of patients (n = 18) with both hepatic and peritoneal metastases, and this group did not benefit from IORT (IORT, n = 6; no IORT, n = 12) in terms of survival. Similarly, there was no significant difference in the survival rates between patients undergoing IORT (n = 10) and patients without IORT (n = 11) in the subgroup of patients with hepatic metastasis but without peritoneal metastasis. However, patients with peritoneal metastasis but without hepatic metastasis benefited significantly from IORT (IORT, n = 8; no IORT, n = 6) (p < 0.05). Pain relief following IORT was observed in 9 out of 10 patients who had experienced pain prior to surgery. CONCLUSION: Pancreatic carcinoma associated with peritoneal metastasis but without hepatic metastasis can be palliated by IORT. In addition, pain palliation in patients who require gastrointestinal or biliary drainage can also be achieved by IORT.     

A phase I/II trial of transurethral surgery combined with concurrent cisplatin, 5-fluorouracil and twice daily radiation followed by selective bladder preservation in operable patients with muscle invading bladder cancer

PURPOSE: We describe a protocol designed to evaluate the use of twice daily radiation used together with cisplatin and 5 fluorouracil (5-FU) in the treatment of operable transitional cell carcinoma of the bladder with potential bladder preservation. MATERIALS AND METHODS: A total of 18 consecutive patients with T2-T4a bladder tumors underwent as complete a transurethral resection as possible, which was visibly complete in 14 cases. They then received twice daily radiation and infusion cisplatin and 5-FU during an induction phase. No therapy was given for 3 weeks, following which patients were reevaluated cystoscopically. Cases of clinical complete response by biopsy and cytology were consolidated with further chemotherapy/radiation using the same chemotherapeutic agents and radiation schedule. Patients who had incomplete responses were advised to undergo an immediate radical cystectomy. Of the 18 patients 15 subsequently received 3 cycles of adjuvant chemotherapy, consisting of methotrexate, cisplatin and vinblastine. Median followup for the entire group is 32 months. RESULTS: Of the 18 patients 14 had no detectable tumor after induction therapy. Of the 4 patients with persistent tumor 2 underwent radical cystectomy and 2 refused cystectomy, 1 of whom was treated with partial cystectomy and the other with consolidation chemotherapy/radiation. The actuarial overall survival at 3 years was 83%. The chance of a patient being alive at 3 years with a native bladder was 78%. No patient required cystectomy for hematuria or bladder shrinkage. Three patients in whom superficial tumors developed were treated successfully with bacillus Calmette-Guerin. Small bowel obstruction in 1 case was corrected surgically. CONCLUSIONS: This pilot study demonstrates a high rate of response to this combined chemotherapy/radiation regimen in conjunction with a visibly complete transurethral resection. Reevaluation after a short induction phase allows for the early selection of patients with persistent disease for radical cystectomy.     

Verrucous carcinoma of the oral cavity: management by radiotherapy and surgery

Verrucous carcinoma is a distinct nonmetastasizing variant of well differentiated squamous cell carcinoma. It is frequently found in the oral mucosa, often in association with the more common type of metastasizing squamous cell carcinoma. In many centres radiotherapy is not used to treat verrucous carcinoma because this tumour is thought to be radioresistant and because "anaplastic transformation" has been reported following such therapy. In a series of 37 patients, 30 received radiotherapy, either alone or combined with surgery. Anaplastic transformation was not encountered. The best results were obtained with aggressive treatment which included both surgery and radiotherapy.     

Comparison of outcomes following transhiatal or Ivor Lewis esophagectomy for esophageal carcinoma

Transhiatal esophagectomy (THO) may be a valid alternative to the traditional Ivor Lewis (ILO) procedure, but there have been reservations about procedure mortality, nodal clearance, and survival. ILO is preferred for bulky midesophageal lesions and THO in frail patients, making randomization difficult. This retrospective study compares results of a 10-year period from January 1985 with a minimum follow-up period of 12 months. Four patients were lost to follow-up. Preoperative nutritional markers were similar in the two groups, as were the age and sex distribution. Altogether 33 ILOs and 65 THOs were performed. TNM staging was similar between groups, there being 43% stage II and 45% stage III lesions among the ILO patients and 53% stage II and 32% stage III disease in the THO group. Operating time was shorter for THO (256 +/- 58 minutes vs. 279 +/- 50 minutes) (p = 0.05); if two surgeons operated concurrently, THO could be performed 40 minutes quicker than THO or ILO performed by a single surgeon (p = 0.018). The mean initial intensive care unit stay was 2.9 days for ILO versus 1.7 days for THO (p = 0.014). The 30-day mortality was 5.1%; total in-hospital mortality was 7.1% with no difference for operation type. There were similar morbidity rates for the procedures. Kaplan-Meier survival analysis indicated no significant effect of surgical technique; there were no apparent advantages for either operation when patients were compared by tumor type or matched for stage. Hence THO is a valid alternative to ILO, particularly for stage II and III cancer.     

Induction chemotherapy, surgery, and concomitant chemoradiotherapy for carcinoma of the esophagus: a long-term analysis

OBJECTIVE: To examine intrarater reliability in measurements of active range of motion and passive range of motion of shoulder flexion and abduction when motions are assessed in sitting, as compared with supine. DESIGN: Thirty adult subjects were measured eight times, in random order, for each of the two shoulder motions: two passive and two active measurements while sitting, and two passive and two active measurements while supine. Data were analyzed to determine intraclass correlation coefficients (ICCs) and paired t values between trials 1 and 2 for measurements in the same position, and between sitting and supine trials for each type of measurement. SETTINGS: Rehabilitation facility and university. STUDY POPULATION: Volunteer sample: 11 rehabilitation inpatients; 19 university students. RESULTS: ICCs between trials 1 and 2 on comparable measurements in the same position indicated high intrarater reliability for active and passive measurements, regardless of testing position. ICCs between comparable measurements in the two testing positions indicated only a moderate level of agreement. Paired t tests between comparable readings taken in sitting versus supine revealed no significant differences for flexion, but significantly higher measurements of abduction when testing in the supine position. CONCLUSIONS: Measurements in sitting or supine yield similarly high intrarater reliability. Lowered reliability between measurements taken in different positions indicates that test position should be routinely recorded, and repeated clinical measures of individual subjects should be administered in a consistent position.     

Management for stage II glottic carcinoma: radiation therapy or surgery

AIM: To analyze the results of stage II glottic carcinoma treated with radiotherapy or surgery. PATIENTS AND METHOD: One hundred thirty-four patients with squamous cell carcinoma of the T2N0M0 glottic carcinoma treated at the Osaka Medical Center for Cancer and Cardiovascular Diseases from 1979 through 1991 were reviewed. The 5-year disease-free survival and laryngeal preservation rate and prognostic factors were examined. Treatment was radiation therapy with salvage surgery for failure or surgery alone. RESULTS: The 5-year disease-specific survival rate for the radiotherapy group was 100% and for the surgery group, 93% (p = 0.055). In the surgery group 5-year disease-specific survival rate for the subgroup of cord mobility was 94% and that of impaired cord mobility, 89% (p = 0.5354). Concerning laryngeal preservation the radiotherapy group showed better preservation rate than the surgery group in the subgroup of cord mobility, i.e., 41/51 (80%) versus 6/55 (11%) (p < 0.001) although significant difference was not observed in the lesion with impaired cord mobility, 2/5 versus 4/22 (p = 0.171). CONCLUSION: We recommend radiation therapy for stage II glottic carcinoma with normal cord mobility, although further study is needed to improve the preservation rate of the larynx with keeping the disease-specific survival for the lesion with impaired cord mobility.     

Hypofractionated radiotherapy with concurrent 5-fluorouracil radiosensitisation for recurrent or locally advanced colorectal cancer. A phase II study

In a pilot study we treated 19 patients suffering from recurrent or locally advanced inoperable colorectal cancer, with concurrent hypofractionated radiotherapy (4-5 Gy/fraction, 2 fractions per week) and 5-fluorouracil bolus, 1 hour before RT at doses of 300 mg/m2. For 16 patients treated with radical intent the Normalised Total Dose for alpha/beta = 10 Gy ranged between 56-74 Gy (median 62 Gy). The schedule used was very well tolerated. Moderate grade II haematological toxicity was observed in 11% of cases and diarrhoea grade II/III resulting in 2-4 weeks treatment delay was observed in 26% of cases. One case with bowel perforation and one with painful subcutaneous fibrosis was observed during 12-27 months of follow-up. Out of 16 patients treated with radical intent 4 (25%) showed complete response and the overall response rate was 56% (9/16). The one-year symptom-free survival was obtained in 11/16 (69%) radically treated patients. It is concluded that hypofractionated radiochemotherapy with 5-fluorouracil for recurrent or locally advanced colorectal cancer is an effective regimen and has acceptable acute and late toxicity. Further investigation is required.