Survival after attempted surgical resection and intraoperative radiation therapy for pancreatic and periampullary adenocarcinoma

PURPOSE: To evaluate a single institution's experience with intraoperative radiation therapy (IORT) in combination with attempted surgical resection for pancreatic and periampullary adenocarcinoma. METHODS AND MATERIALS: From May 1986 until June 2001, 77 patients at LDS Hospital underwent attempted surgical resection and IORT for pancreatic or periampullary adenocarcinoma. A potentially curative resection was defined as surgery with negative or microscopic positive margins. No patients had metastatic disease at the time of surgery and IORT. Forty-four patients with tumors located in the pancreas and 9 patients with periampullary tumors underwent potentially curative surgical resection and IORT. Twenty-four patients had pancreatic tumors deemed unresectable and underwent surgical bypass and IORT. Actuarial survival was calculated from the date of IORT until last follow-up or death by use of the Kaplan-Meier method. RESULTS: Patients undergoing a potentially curative resection and IORT for periampullary adenocarcinoma had a median survival of 167 months and a 56% 5-year actuarial survival, compared with a median survival of 16 months and a 19% 5-year actuarial survival for patients undergoing the same treatment for pancreatic adenocarcinoma (p = 0.03). Patients with unresectable disease who underwent bypass and IORT had a median survival of 11 months and a 0% 3-year survival, significantly worse than patients able to undergo surgical resection and IORT (p = 0.0002). The operative mortality for all patients undergoing potentially curative resection and IORT was 3.7%. CONCLUSIONS: Intraoperative radiation therapy is well tolerated and does not increase the morbidity or mortality of potentially curative surgical resection for pancreatic or periampullary adenocarcinoma. Patients with periampullary adenocarcinoma have a better prognosis than those with pancreatic adenocarcinoma, and patients with unresectable pancreatic disease fared worse.     

Preoperative chemoradiation in adenocarcinoma of the pancreas. A single centre experience advocating a new treatment strategy

Aims

To evaluate a single centre's experience with pancreatic carcinoma focused on preoperative chemoradiation therapy (CRT) for treatment of locally advanced pancreatic carcinoma. The aim of the present analysis was to evaluate the median overall survival time (OS) after preoperative CRT and to compare it with OS after primary resection of pancreatic carcinoma. In conclusion a new treatment strategy was developed using multimodality treatment for pancreatic carcinoma deemed to be resectable by CT-scan.

Patients and methods

Between 1995 and 2003, 302 patients with ductal adenocarcinoma of the pancreatic head and body were recorded prospectively and OS was analysed with regard to therapy.

Results

Fifty-eight patients were resected without any pretreatment and had an OS of 21 months. Twenty-one patients with initially unresectable tumours underwent CRT followed by resection and had an OS of 54 months, which was not significantly different from primary resection (p = 0.315). Lymph node metastasis was significantly reduced after CRT (p = 0.0029). OS for patients whose tumours could not be resected was 3–10 months, depending on tumour stage and consecutive therapy.

Conclusion

CRT pretreatment was effective in locally advanced pancreatic carcinoma and resulted in resection of tumours otherwise staged as non-resectable. This experience led to a randomized trial for patients who by CT are staged to have resectable cancer of the pancreatic head with the intent to increase curative resectability and survival by neoadjuvant CRT (ISRCTN78805636/NCT00335543).     

Interventional endoscopy,neoadjuvant therapy and the gastroenterologist

With current treatment, survival of greater than 1 year should be anticipated for many patients with pancreatic cancer. Cure rates (5-year survival) of greater than 10% have been achieved even for unresectable disease. Obstructive jaundice is managed successfully with endoscopic placement of a plastic stent early in the evaluation of a patient with suspected regional pancreatic cancer, and a metal wall stent is reserved for patients with known 1997 AJCC stage IVB carcinoma or nonoperative patients. Relief of biliary obstruction allows improvement in liver function and more time to evaluate tumor stage accurately to determine initial treatment (see Fig. 1). A cost-effective algorithm to determine accurate stage and treatment can start with the size of the mass on initial imaging studies. EUS-guided FNA represents a significant improvement over CT scan-guided FNA to make a tissue diagnosis. Small pancreatic masses that would be resected regardless of whether an FNA is positive or negative require only an EUS evaluation to establish an early resectable stage. Tumors reliably staged as unresectable by nonoperative imaging methods including EUS are treated with chemotherapy with or without concurrent radiotherapy because median survival of these patients is 2 years in some series. Tumors can be resected after neoadjuvant chemoradiotherapy. For chronic pain or gastric outlet obstruction not responding or treatable by chemoradiotherapy, endoscopically guided celiac plexus nerve block and stenting improve the quality of life for patients with pancreatic cancer. A team approach is required to achieve the objectives of improved quality of life, prolonged survival, and possible cure for pancreatic cancer. The optimal combination and sequencing of staging methods, including EUS, specialized CT scan, MR imaging, intraoperative findings, and pathologic evaluations, would improve selection of patients for potential curative resection. Interpretations of disease stage based on each of these methods may overlap but are not identical and are operator dependent. Rather than reliance on any single standard, clinical judgment and communication among the team are paramount to providing optimal care for patients with a pancreatic neoplasm.     

Radical reoperation for advanced pancreatic carcinoma

The indications and outcomes of aggressive reoperation in patients referred to the National Cancer Institute (NCI) for protocol therapy of locally advanced pancreatic carcinoma were investigated. Twenty-nine patients referred to the NCI after exploration and determination of unresectability elsewhere were considered to have localized disease after a metastatic work-up. These patients were then entered onto NCI adjuvant therapy protocols and taken to exploratory laparotomy. Intraoperatively, patients underwent complete resection if possible; otherwise varying palliative surgical procedures were performed. Of the 29 patients, 16 underwent complete resection of their disease, and 13 were unresectable. Two patients suffered postoperative mortality. Disease-specific survival of the resected patients was significantly better than that of the unresectable patients (P < 0.01). The two long-term survivors (53 and > 109 months) underwent definitive surgery after a palliative procedure elsewhere. Complete resection of pancreatic carcinoma contributes to increased survival. The intraoperative definition of unresectability in pancreatic cancer varies with the degree of pancreatitis present, the surgical expertise of the surgeon, and the available ancillary services. Given the extremely grave prognosis of patients with unresectable pancreatic carcinoma, locally unresectable patients without peritoneal seeding or distant metastases at exploration should be considered for referral for protocol therapy to centers where expertise in radical surgery for pancreatic cancer exists. (This article is a US Government work and, as such, is in the public domain in the United States of America.) © 1996 Wiley-Liss, Inc.     

Surgical resection after preoperative chemoradiotherapy benefits selected patients with unresectable pancreatic cancer

Simultaneous chemoradiation is used in unresectable pancreatic cancer for palliation. It is not known if the use of adjuvant surgery will benefit this group of patients. From November 1991 to September 1998, 47 patients with unresectable pancreatic cancer were treated with simultaneous preoperative radiation therapy (45 Gy) and chemotherapy. Chemotherapy followed three different protocols: cisplatin, 5-fluorouracil +/- paclitaxel; cisplatin, 5-fluorouracil (protracted infusion); and docetaxel and gemcitabine. Whipple pancreatoduodenectomy was performed 1 month after the end of radiation in patients selected for resection. Twenty-three unresectable tumors after preoperative treatment (47%) received an additional dose (10-12 Gy) of radiotherapy using intraoperative or external radiation therapy. Twelve patients (26%) were considered to have clinically resectable tumors after the preoperative treatment. Nine patients had surgery (19% of the total number of patients), and 2 of them had complete pathologic response. After chemoradiation, two patients died of pneumonia and gastrointestinal bleeding, respectively, and another two patients died in the postoperative period. Local recurrence was observed in 22% of the patients and 57% had distant metastases. Three-year survival rates for patients with unresectable and resectable tumors was 0% (median survival 10 months) and 48% (median survival 23 months), respectively (p = 0.0004). Preoperative treatment with chemotherapy and radiotherapy in patients with unresectable pancreatic cancer is feasible. In some patients, the tumor can be resected, and in addition some cases of complete pathologic response were found. Long-term survivors were observed in the group of resected tumors. More effective chemotherapy regimens are needed because the majority of the patients died of metastatic disease.     

Gemcitabine following radiotherapy with concurrent 5-fluorouracil for nonmetastatic adenocarcinoma of the pancreas

Gemcitabine has been shown to be an active agent in the treatment of pancreatic cancer. This study was conducted to prospectively examine the tolerance and early efficacy of adjuvant gemcitabine following radiotherapy with concurrent 5-fluorouracil (5-FU) for nonmetastatic pancreatic adenocarcinoma. Twenty-three patients, median age 64 years, were treated with combined modality therapy. Nine patients underwent tumor resection before chemoradiation; 14 patients with locally unresectable tumors received definitive chemoradiation. Radiotherapy utilized four fields to the tumor and lymphatics to 45 Gy, plus a lateral boost to 50.4 Gy. Concurrent 5-FU 500 mg/m(2)/day was administered on days 1-3 and 29-31, followed by 4 months of gemcitabine 1,000 mg/m(2)/week for 3 weeks (fourth week break). Adjuvant gemcitabine was well tolerated. Eighty-three percent of the patients completed three to four cycles. The primary dose-limiting toxicity was leukopenia, which was observed in 10 patients (43%). Nonhematologic toxicities were reported in five patients (22%). There were no cases of gemcitabine-induced radiation recall and there have been no deaths attributed to treatment toxicity. Median follow-up for the 23 patients was 12 months (range, 5-50); the actuarial median survival was 13 months. This report confirms that adjuvant gemcitabine following radiotherapy with concurrent 5-FU for nonmetastatic pancreatic adenocarcinoma can be safely administered.     

Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma.

PURPOSE: In the West, curative (R0) resection is achieved in approximately 50% of patients with localized gastric carcinoma, and more than 60% die of cancer following an R0 resection. A multi-institutional study of preoperative chemoradiotherapy was done to assess the R0 resection rate, pathologic complete response (pathCR) rate, safety, and survival in patients with resectable gastric carcinoma. PATIENTS AND METHODS: Operable patients with localized gastric adenocarcinoma were eligible. Staging also included a laparoscopy and endoscopic ultrasonography (EUS). Patients received up to two 28-day cycles of induction chemotherapy of fluorouracil, leucovorin, and cisplatin, followed by 45 Gy of radiation plus concurrent fluorouracil. Patients were then staged and surgery was attempted. RESULTS: Thirty-four patients were registered at three institutions. One ineligible patient was excluded. Most patients had a promixal cancer and EUST3N1 designation. Twenty-eight (85%) of 33 patients underwent surgery. The R0 resection rate was 70% and pathCR rate was 30%. A pathologic partial response (< 10% residual carcinoma in the primary) occurred in eight patients (24%). EUS T plus N and postsurgery T plus N correlation showed significant downstaging (P = <.01). The median survival time for 33 patients was 33.7 months. Patients achieving a pathCR or pathPR had a significantly longer median survival time (63.9 months) than those achieving less than pathPR (12.6 months; P =.03). There were two treatment-related deaths. CONCLUSION: Our data suggest that the three-step strategy of preoperative induction chemotherapy followed by chemoradiotherapy resulted in substantial pathologic response that resulted in durable survival time. This strategy is worthy of a direct comparison with postoperative adjuvant chemoradiotherapy.     

Adjuvant chemoradiation for patients with adenocarcinoma of the pancreas: an expirence of single institute

Only a small percentage of patients with pancreatic cancer have limited disease suitable for curative resection. Even with surgery, patients often have poor long-term survival due to relapse of the disease. There are controversies about the adjuvant treatment of these patients. We reported the survival of resected pancreatic cancer from a single institute. About 128 consecutive patients who had complete resection of the pancreatic ductal adenocarcinoma were evaluated, retrospectively. Chemoradiotherapy (45 Gy plus 5-fluorouracil) was given to 63 patients. Fifty-five patients declined to take chemoradiotherapy or with poor performance status were observed without additional treatment. Eight patients took only chemotherapy and two patients took only radiotherapy. The median survival of chemoradiotherapy group was significantly higher than the observation group (13 months vs. 4 months, respectively; P < 0.001). In multivariate analyses the most important factors improving survival were the application of chemoradiation (P < 0.001), low-level serum LDH (P = 0.026), good performance status (P = 0.033) and low serum CA19-9 (P = 0.037). Although adjuvant chemoradiotherapy has a significant survival benefit when compared with the observation group, the survival data are still poor for pancreatic cancer. Therefore, we need more effective additional or adjuvant treatment modalities.     

Surgical treatment of pancreatic adenocarcinoma; actual survival and prognostic factors in 343 patients

Survival data of patients with pancreatic carcinoma are often overestimated because of incomplete follow-up. Therefore, the aim of this study was to approach complete follow-up and to analyse survival and prognostic factors of patients who underwent surgical treatment for pancreatic adenocarcinoma. Between 1992 and 2002, 343 patients underwent surgical treatment for pancreatic adenocarcinoma. One hundred and sixty patients underwent a resection with a curative intention and 183 patients underwent bypass surgery for palliation. Follow-up was complete for 93% of patients. Median survival after resection and bypass was 17.0 and 7.5 months, and 5-year survival was 8% and 0, respectively. In multivariate analysis, tumour-positive lymph nodes, non-radical surgery, poor tumour differentiation, and tumour size were independent prognostic factors for survival after resection. For patients treated with bypass surgery, metastatic disease and tumour size independently predicted survival. In conclusion, actual survival of patients with pancreatic adenocarcinoma is disappointing compared with the actuarial survival rates reported in the literature. The independent prognostic factors for survival of patients who underwent surgical treatment for pancreatic adenocarcinoma are tumour-related.     

Value of CT criteria in predicting survival in patients with potentially resectable pancreatic head carcinoma

BACKGROUND AND OBJECTIVE: Survival is often poor after resection of pancreatic tumors. We correlated the pre-operative CTs with survival to find criteria that have prognostic value. To establish the prognostic value of CT in patients with potentially resectable pancreatic head carcinoma. METHODS: In 71 consecutive patients with potentially resectable pancreatic head carcinoma, prognostic factors on CT were scored, for example, tumor size, peripancreatic infiltration, grades of vascular encasement, and local irresectability. All patients underwent surgical exploration. CT findings were compared with results of surgery and histopathology. Prognostic factors for resected and unresected tumors were analyzed using single and multivariate analysis. RESULTS: Forty-one of 71 tumors were resected (24 radical). The sensitivity, specificity, and positive predictive value of CT for surgical irresectability were 0.67, 0.63, and 0.57, respectively. For a non-radical resection, these were 0.62, 0.75, and 0.83, respectively. The median survival was 21 months for resectable tumors and 9.7 months for unresectable tumors. For resected tumors, a tumor diameter of > 3 cm (relative hazard 3.8) and CT signs of local unresectability showed a poor survival. The median survival of resected tumors <2 cm was nearly 30 months. CONCLUSION: CT signs of local irresectability and a tumor diameter of >3 cm predict a poor survival after resection.     

Intensity-modulated radiotherapy in treatment of pancreatic and bile duct malignancies: toxicity and clinical outcome

PURPOSE: To assess the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) in pancreatic and bile duct (cholangiocarcinoma) malignancies. METHODS AND MATERIALS: Twenty-five patients with pancreatic and bile duct cancer were treated with IMRT. Twenty-three received concurrent 5-fluoruracil. One patient with a pancreatic primitive neuroectodermal tumor received concurrent etoposide and ifosfamide. Eight patients had resected tumors, and 17 had unresectable primary (n = 14) or recurrent (n = 3) tumors. Six patients underwent treatment planning with conventional three-dimensional four-field techniques for dosimetric comparison with IMRT. RESULTS: Compared with conventional RT, IMRT reduced the mean dose to the liver, kidneys, stomach, and small bowel. IMRT was well tolerated, with 80% experiencing Grade 2 or less acute upper GI toxicity. At a median follow-up of 10.2 months, no resected patients had local failure, and only 1 of 10 assessable patients with unresectable cancer had local progression. The median survival and distant metastasis-free survival of the 24 patients with adenocarcinoma was 13.4 and 7.3 months, respectively. Grade 4 late liver toxicity occurred in 1 patient surviving >5 years. The remainder of the assessable patients experienced no (n = 9) or Grade 1 (n = 4) late toxicity. CONCLUSION: In this hypothesis-generating analysis, the acute and chronic toxicity profile with IMRT in the treatment of pancreatic and bile duct cancer was encouraging. Local control was not compromised, despite efforts to increase conformality and avoid doses to normal structures. Distant failure remains a major obstacle in pancreatic cancer.     

Patterns of treatment failure and prognostic factors associated with the treatment of esophageal carcinoma with chemotherapy and radiotherapy either as sole treatment or followed by surgery .

PURPOSE: The records of patients with esophageal cancer who were treated with a combined modality therapy were reviewed to determine the effects of simultaneously administered chemotherapy and radiotherapy (RT) at sites of recurrence and the relationship between treatment outcome and clinicopathologic variables. PATIENTS AND METHODS: One hundred seventeen patients were treated with fluorouracil (800 mg/m2) [corrected] and cisplatin (80 mg/m2) combined with either 36 Gy (36 patients) or 54 to 60 Gy (35 patients) of RT as sole therapy. Forty-six patients underwent surgery after they had received chemotherapy and 36 Gy of RT as initial treatment. Patients with either squamous cell cancer (SCC) or adenocarcinoma were included. RESULTS: Complete endoscopic regression after an initial 36 Gy of RT and chemotherapy occurred in more than 50% of patients and in both tumor types. Relief of dysphagia accompanied tumor regression. Forty-two tumors were resected, and 11 showed a complete histologic response. Significant associations were demonstrated between enhanced survival and a diagnosis of SCC, a complete endoscopic response to initial chemotherapy and RT, and a tumor length of less than 5 cm. Multivariate analyses suggested that tumor length and complete endoscopic response were independent prognostic variables. The survival rate of patients treated by resection or radical-dosage RT was not significantly different. CONCLUSIONS: The relief of dysphagia demonstrates the palliative value of chemotherapy and RT in both tumor types. The similar survival rates of patients with SCC or adenocarcinoma treated either surgically or with high-dose combined therapy (54 to 60 Gy) emphasize the need to evaluate the role of surgery and combined treatment in randomized studies.     

Successful treatment with cetuximab combination chemotherapy in a case of FOLFOX-refractory rectal cancer with previously unresectable multiple liver metastases leading to complete resection

Most colorectal cancer patients with liver metastases are not resectable upon initial diagnosis. Recently, chemotherapy improves overall survival of initially unresectable patients by allowing tumor downstaging and complete resection. We report a FOLFOX-refractory rectal cancer patient with unresectable multiple liver metastases, whose tumors could be downstaged and completely resected after initiation of FOLFIRI with cetuximab. Case: A 41-year-old male demonstrated rectal cancer with unresectable multiple liver metastases. He was treated by FOLFOX4 therapy as first-line chemotherapy. After initiating 14 courses, he was treated by FOLFIRI with cetuximab because of disease progression. After initiation of chemotherapy, radiographic examination demonstrated remarkable reduction of primary rectal tumor and metastatic liver tumors. He underwent complete rectal tumor resection after 13 courses of chemotherapy, and metastatic liver tumor resection after 18 courses of chemotherapy.     

Locally advanced pancreatic adenocarcinoma. Chemoradiotherapy, reevaluation and secondary resection]

Induction chemoradiotherapy (CRT) may downstage locally advanced pancreatic tumors but secondary resections are unfrequent. However some responders' patients may benefit of a R0 resection. PATIENTS AND METHODS: We report 18 resections among 29 locally advanced pancreatic cancers; 15 patients were treated with neoadjuvant 5-FU-cisplatin based (13) or taxotere based (2 patients) chemoradiotherapy (45 Gy), and 3 patients without histologically proven adenocarcinoma were resected without any preoperative treatment. RESULTS: The morbidity rate was 28% and the mortality rate was 7%; one patient died after resection (5.5%) and one died after exploration (9%). The R0 resection rate was 50%. The median survival for the resected patients was not reached and the actuarial survival at 3 years was 59%. Two specimens showed no residual tumor and the two patients were alive at 15 and 46 months without recurrence; one specimen showed less than 10% viable tumoral cells and the patient was alive at 36 months without recurrence. A mesenteric infarction was the cause of a late death at 3 years in a disease free patient (radiation induced injury of the superior mesenteric artery). The median survival of the 11 non-resected patients was 21 months and the actuarial survival at 2 years was 0%. When the number of the resected patients (18) was reported to the entire cohort of the patients with locally advanced pancreatic cancer treated during the same period in our institution, the secondary resectability rate was 9%. CONCLUSION: Preoperative chemoradiotherapy identifies poor surgical candidates through observation and may enhance the margin status of patients undergoing secondary resection for locally advanced tumors. However it remains difficult to evaluate the results in the literature because of the variations in the definitions of resectability. The best therapeutic strategy remains to be defined, because the majority of patients ultimately succumb with distant metastatic disease.     

Clinical experience with chronomodulated infusional 5-fluorouracil chemoradiotherapy for pancreatic adenocarcinoma

PURPOSE: To evaluate retrospectively the efficacy and chronic toxicities of concurrent radiotherapy and chronomodulated infusion 5-fluorouracil (5-FU) in patients with pancreatic adenocarcinoma. METHODS AND MATERIALS: Twenty-eight patients with pancreatic adenocarcinoma were treated between January 1997 and May 2000 with 5-FU chronomodulated chemoradiotherapy. Chronomodulated delivery of chemotherapy was chosen on the basis of a lower toxicity profile in the treatment of GI malignancies. The median age was 64 years. Of the 28 patients, 12 were men and 16 were women. Eight patients had unresectable disease and 20 were treated after pancreatic resection. The median radiation dose was 50.4 Gy given in 28 fractions. The median field length and width was 10.6 cm and 10.9 cm, respectively. Concurrent chemotherapy with 5-FU was administered 5 d/wk, with a median total dose of 8.4 g/m2 (300 mg/m2/d). Chronomodulated 5-FU delivery consisted of a low basal infusion for 16 h followed by an 8-h escalating-deescalating infusion peaking at 10 pm. Survival and recurrence data were evaluated using Kaplan-Meier actuarial analysis. Toxicities were recorded using the Radiation Therapy Oncology Group grading system. RESULTS: The median follow-up for all patients was 26 months (range, 4-68 months). The median overall survival for the 20 patients treated postoperatively was 34 months, with a 3- and 5-year actuarial survival rate of 40% and 21%, respectively. If the 3 patients with carcinoma of the ampulla were removed from the data set, the mean overall survival in the resected patients was 34 months, with a 3-year and 5-year actuarial survival rate of 40% and 17%, respectively. The 8 unresectable patients had a median overall survival of 14 months, and none lived past 2 years. No patient experienced Grade 3 or 4 hematologic toxicity or weight loss. Five patients had nausea and dehydration requiring i.v. fluids; only one (4%) was hospitalized. Four patients required a dose reduction of 5-FU, one for nausea, one for a transient ischemic attack, one for an infection, and one because of myocardial infarction. Seven resected patients, four of whom had no evidence of disease, developed diabetes mellitus 1-2 years after radiotherapy. CONCLUSION: Chronomodulated 5-FU administration, based on the concept of chronotolerance, has relatively low acute toxicity. Our median survival rate was greater than that after most chemoradiotherapy programs that result in more acute toxicity. Additional study is warranted to evaluate chronomodulated radiosensitizing chemotherapy schedules in prospective trials and with attention to late effects after radiotherapy, including diabetes mellitus.     

食管癌术前放化疗临床研究进展

手术治疗是可切除食管癌的标准治疗方案,但对局部晚期食管癌,同步放化疗显示了良好的疗效。但是同步放化疗治疗食管癌存在较多的局部区域复发,影响了患者的生活质量。多个大型前瞻性随机分组研究提示,无论是食管鳞状细胞癌还是腺癌,联合应用同步放化疗及手术治疗有望进一步提高患者生存质量,延长患者的生存期。目前常用的同步化疗方案为顺铂及氟尿嘧啶方案,而放疗剂量及靶区不一。研究显示同步放化疗后病理例完全缓解者生存率明显提高,因而疗前预测食管癌患者同步放化疗的敏感性具有重要的地位,可以选择对放化疗抗拒的食管癌患者直接接受手术治疗,避免同步放化疗的不良反应及治疗时机的延搁。目前的常规临床检查手段难以预测及早期判别同步放化疗的疗效,联合应用分子生物标记物有望选择放化疗敏感的患者接受术前放化疗,而对放化疗不敏感的患者则直接接受手术治疗,从而实现食管癌患者的个体化治疗。      

Malignant tumors of the anal canal: the spectrum of disease, treatment, and outcomes

BACKGROUND: Cancers of the anal canal are a rare and diverse group of tumors of the gastrointestinal tract currently managed most often with surgery, chemoradiotherapy, or both. Previous investigations of cancer of the anal canal have reported on small numbers of patients, included only squamous histology, or included a select group of patients. The current study reviewed a large consecutive series of patients with cancer of the anal canal, including all histologies, who received chemoradiotherapy as the primary treatment modality. METHODS: The spectrum of pathology, treatment, and outcomes for 192 patients with malignant tumors of the anal canal over a 10-year period, from 1984 to 1994, was analyzed. Patient charts were reviewed for diagnosis, staging, treatment, survival, and recurrence rates. RESULTS: The pathologies of 192 patients (mean age, 58 years; 119 females and 73 males) included 143 (74%) with squamous cell carcinoma, 36 (19%) with adenocarcinoma, and 7 (4%) with melanoma. The remaining 6 patients (3%) were diagnosed with neuroendocrine tumors (2), carcinoid tumor (1), Kaposi sarcoma (1), leiomyosarcoma (1), or lymphoma (1). T classification distributions were T1 (3%), T2 (46%), T3 (28%), and T4 (12%). The overall crude 5-year survival and recurrence rates were 53% and 34%, respectively. Five-year survival rates were 57% for squamous cell carcinoma, 63% for adenocarcinoma, and 33% for melanoma. Five-year survival rates by T classification were T1 (62%), T2 (57%), T3 (45%), and T4 (17%). Twenty-one (15%) of the patients with squamous cell carcinoma underwent surgical therapy only, with a 5-year survival rate of 60% and a recurrence rate of 23% at 5 years. The remaining 122 patients (85%) with squamous cell carcinoma received chemoradiotherapy only, with a 5-year survival rate of 55% and a recurrence rate of 34% at 5 years. Salvage abdominal perineal resection for recurrent or persistent squamous cell carcinoma after chemoradiotherapy was performed on 13 patients, with 8 (62%) of them alive at a mean follow-up of 32 months. Twenty-two patients (61%) with adenocarcinoma of the anal canal were treated with surgery, and 14 patients (39%) underwent surgery with adjuvant chemoradiation therapy. The 5-year survival and recurrence rates were 63% and 21%, respectively. CONCLUSIONS: Chemoradiotherapy for patients with squamous cell carcinoma offers survival rates equivalent to surgical therapy and preserved sphincter function. Adenocarcinoma managed with surgery, with adjuvant therapy for selected patients, gives good results. Melanoma continues to be associated with a poor prognosis.     

A phase II trial of preoperative concurrent radiation therapy and weekly paclitaxel/carboplatin for patients with locally advanced non-small-cell lung cancer

This study was designed to evaluate the efficacy and toxicity of a novel preoperative combined-modality regimen in patients with locally advanced non-small-cell lung cancer (NSCLC). Patients with clinical stage IIB, IIIA, or IIIB NSCLC received preoperative combined-modality therapy with concurrent radiation therapy (RT) and weekly paclitaxel/carboplatin for 5 consecutive weeks. After this treatment, patients believed to have resectable disease by standard surgical criteria underwent thoracotomy. Patients whose disease remained unresectable after initial therapy received further RT with concurrent paclitaxel/carboplatin. Of 107 patients entered into this clinical trial, only 20 patients (19%) were considered to have surgically resectable disease at the time of study entry. Ninety-eight patients (92%) completed preoperative combined-modality therapy. Forty-nine patients (46%) underwent thoracotomy and 34 patients had definitive resection. Fourteen patients (13%) had pathologic complete response (pCR). Thirteen of 18 patients (72%) with clinical stage T3 N0 (IIB) tumors had definitive resections, and 33% had pCR. After a median follow-up of 32 months, the 1- and 2-year actuarial survival rates for the entire group are 64% and 42%, respectively. Favorable-prognosis subgroups included patients who had definitive resection and patients with clinical stage T3 N0 tumors (2-year survival rates of 67% for both subgroups). Preoperative therapy with RT and weekly paclitaxel/carboplatin showed activity in this patient population; however, disease in the majority of patients with extensive involvement of mediastinal nodes remained unresectable after this treatment. Results in patients who initially had unresectable disease do not appear different than results achieved with concurrent RT/chemotherapy approaches. Postoperative complications associated with this preoperative combined-modality regimen were more frequent than expected with resection alone.     

局部晚期胃癌放化疗不同联合方式及放化疗转化手术治疗的疗效分析

目的:观察分析不能手术局部晚期胃癌放化疗联合的临床疗效及转化治疗疗效,对比不同放化疗联合模式的疗效差异。 方法:回顾性分析2010年06月至2020年06月于我院收治的不能手术的局部晚期胃癌患者75例,其中同步放化疗组33例,序贯放化疗（化疗－放疗－化疗）组42例,观察放化疗联合的临床疗效及转化治疗成功率,对比分析两种治疗方式的临床效果。结果:客观有效率（ORR）53.3%,疾病控制率（DCR）85.3%,转化手术切除率30.7%;同步放化疗组与序贯放化疗组的ORR分别为66.7%和42.9%,差异有统计学意义（P＜0.05）;同步放化疗组转化手术成功率优于序贯放化疗组（36.4% vs 26.2%）,但差异没有统计学意义（P＞0.05）;未手术患者中位生存时间（MST）为14.3个月,1、2年生存率分别为63.5%,15.4%,同步放化疗组生存优于序贯放化疗组,但差异无统计学意义（P＞0.05）;转化手术成功的患者中,R0切除的生存明显优于行R1/R2切除患者（P＜0.05）。结论:对于初始不能手术的局部晚期胃癌,联合放化疗是有效的治疗手段,同步放化疗较序贯放化疗明显提高了客观有效率,有提高转化手术切除率的趋势。     

Radiation therapy for unresectable rectal cancer

The standard approach to patients with unresectable rectal cancer is pre-op radiation therapy followed by surgery. To determine the impact of RT on local failure and survival, we present an analysis of our preliminary results of this approach in patients with unresectable rectal cancer. A total of 22 patients were analyzed (9 primary, 13 recurrent). The median follow-up was 22 months. There were two groups of patients. Group 1 included 12 patients with unresectable tumors in whom surgery was planned following pre-operative radiation therapy. Group 2 included 10 patients in whom no surgery was planned following radiation therapy due to extensive pelvic bone destruction. The whole pelvis received 4680 cGy followed by a boost of 360-1440 cGy. Six underwent brachytherapy. For the total patient group, the 3-year actuarial survival was 52% (Group 1: 91% vs Group 2: 30%). Patterns of failure as a component of failure were: local failure (or local progression): 50%, abdominal: 23%, and distant: 9%. The dose of pelvic radiation had no significant impact on the local failure rate (5040 cGy: 55% vs greater than 5700 cGy:45%). None of the seven patients with negative margins developed local failure compared with 73% of those with positive margins. The complete resection rate in Group 1 patients was 58%, and all are alive without local failure. Further follow-up will be needed to determine the ultimate local failure and survival rates.