Enhanced staging and all chemotherapy preoperatively in patients with potentially resectable gastric carcinoma.

PURPOSE: Patients with local-regional gastric carcinoma have a low rate of curative resection (R0) because of the advanced stage at diagnosis and suboptimal clinical staging. This study was designed to improve clinical staging with the use of laparoscopy and endoscopic ultrasonography (EUS) and to improve R0 resection rates and tolerance by delivering all chemotherapy preoperatively in patients with potentially resectable gastric carcinoma. PATIENTS AND METHODS: All patients with histologic proof of localized adenocarcinoma of the stomach underwent a staging laparoscopy before registration. EUS was performed when feasible. The intention was to administer up to five courses of preoperative chemotherapy consisting of fluorouracil (500 mg/m(2)/d as a continuous infusion on days 1 through 5 and as a bolus on days 12 and 19), interferon alfa-2b (3 million units subcutaneously three times a week for 3 weeks), and cisplatin (15 mg/m(2)/d as a bolus on days 1 through 5). After chemotherapy, surgery was attempted to remove the primary and regional lymph nodes. Clinical response and EUS staging were correlated with surgical pathology. The feasibility of this approach, resection rates, patient survival, and patterns of failure also were assessed. RESULTS: All 30 patients enrolled were assessed for toxicity, response, and survival. Nineteen men and 11 women were enrolled. The median number of courses delivered per patient was three (range, one to five courses). Fourteen patients (47%) received all five preoperative courses of chemotherapy. The overall clinical response rate was 34%. Twenty-nine patients (97%) underwent attempted resection. Twenty-five (83%) had an R0 resection. Two patients (7%) had no evidence of carcinoma in the surgical specimen, and three had only microscopic carcinoma (>/= 90% necrosis). Posttreatment EUS findings did not correlate well with surgical pathology. The median duration of follow-up was 30 months (range, 5 months to 65+ months). The median survival time for 30 patients, calculated by the Kaplan-Meier method, was 30 months (range, 5 months to 65+ months). There were no cases of grade 4 toxicity. CONCLUSION: It is feasible to administer prolonged preoperative therapy in patients with potentially resectable gastric carcinoma. Enhanced staging with laparoscopy and EUS helped in proper selection of patients and better characterization of the stage.     

Neoadjuvant chemotherapy and preoperative chemoradiotherapy in resectable carcinoma of the rectum

Introduction

The effectiveness of neoadjuvant chemotherapy (Mayo clinic schedule) and continuous oral chemotherapy (tegafur 400 mg and folinic acid 15 mg every 12 hours) administered during preoperative radiotherapy (4,500 cGy over 5 weeks) were studied

Materials and methods

A total of 53 patients with surgically-resectable rectal adenocarcinoma were treated.

Results

Toxicities of ≤ grade II were lower with neoadjuvant chemotherapy while the chemoradiotherapy had higher toxicity rates including grade III diarrhoea (4%), grade III mucositis (4%), and grade III–IV neutropenia (9%). Symptom improvement ocurred in 38% of patients after neoadjuvant chemotherapy coparative with 55% following the first week of chemoradiotherapy. Surgery was curative in 97% of the patients: abdominoperineal amputation in 24 patients (47%) and conservative surgery in 28 (53%). Down-staging ocurred in 24 patients (46%), and 7 patients (14%) showed pathological complete response. Overvall survival at 5 years, with a median follow-up of 50 months, was 70% (cancer-specific survival was 75%) with significant differences recorded between N+ and N0 patients (56% and 76%, respectively; p<0.001), and between T-0-1-2 and T3 patients (73% and 56%, respectively; p<0.001). Only 2 patients (3%) had local relapse.

Conclusion

This treatment scheme was well tolerated and had high rate of local control and longterm times.     

Long-term results with oral fluoropyrimidines and oxaliplatin-based preoperative chemoradiotherapy in patients with resectable rectal cancer. A single-institution experience

Introduction

Neoadjuvant 5-FU-based chemoradiotherapy in resectable rectal cancer (RC) is a standard of treatment. The use of oral fluoropyrimidines and new agents such as oxaliplatin may improve efficacy and tolerance.

Material and methods

Between 1999 and 2009, 126 RC patients with T3?CT4 and/or N+ disease were given three successive protocols: UFT (32), UFT-oxaliplatin (75) and capecitabine-oxaliplatin (19), alongside 45 Gy of radiotherapy; with surgery 4?C6 weeks after. Adjuvant treatment was given in all patients. The primary objective was pathologic complete response (pCR).

Results

Preoperative therapy was well tolerated, with no toxic deaths and a 15% grade 3?C4 toxicity rate. Eighty-five percent of patients received the full chemotherapy dose, 56% had an abdominoperineal resection, 6% reinterventions and 57% received the full adjuvant chemotherapy planned. The pCR rate was 13%. The downstaging rate was 80%; 8% had progression of disease. The relapse rate was 20%, with local relapse in 6%. By 5 years of followup, 92% of relapses had occurred. Median follow-up was 73 months, 5- and 10-year disease-free survival rates were 75% and 50%, and 5- and 10-year overall survival rates were 79% and 66% respectively. There was no benefit from the use of oxaliplatin regarding survival or pCR rates. Older patients had worse long-term outcomes.

Conclusions

Neoadjuvant chemoradiotherapy with oral fluoropyrimidines and oxaliplatin is feasible and well tolerated. The risk of early progression is low. However, there was no added benefit with the use of oxaliplatin. There were no relapses in patients with pCR. The role of adjuvant chemotherapy is unclear.     

The prognostic significance of preoperative serum CA 19-9 in patients with resectable gastric carcinoma: comparison with CEA

BACKGROUND AND OBJECTIVES: In this study, the prognostic value of pre-operative serum levels of tumor markers CA 19-9 and carcinoembryonic antigen (CEA) in gastric carcinoma which has been a controversial matter was investigated. METHODS: Preoperative serum CA 19-9 (cut-off value 37 U/ml) and CEA (cut-off value 5 ng/ml) levels were measured in 168 patients with resectable gastric carcinoma. The correlation between tumor marker levels and clinicopathological features and overall survival was studied. RESULTS: CA 19-9 and CEA positivity rates were 31.5 and 17.8% respectively. In CA 19-9 positive patients, the ratio of males, tumors exceeding subserosa and advanced stage tumors (stages III and IV) was significantly higher (P = 0.052, P = 0.0005 and P= 0.029, respectively). A weak correlation was found with CA 19-9 positivity and tumor location; however, no correlation existed between CA 19-9 positivity and age, tumor size, histologic type, lymph node, hepatic and peritoneal metastasis. The proportion of tumors extending beyond subserosa and with lymph node metastasis was significantly higher in CEA positive patients (P = 0.011 and P = 0.045, respectively). No correlation was found between CEA positivity and gender, age, tumor location, tumor size, and hepatic and peritoneal metastasis; however, a weak correlation existed between CEA positivity and histologic type and tumor stage. Overall survival was significantly poorer in CA 19-9 and CEA positive patients (log-rank test, P = 0.014, P = 0.003, respectively). However, the Cox proportional hazards regression analysis did not show independent prognostic value for both tumor markers. CONCLUSIONS: In resectable gastric carcinoma, preoperative serum CA 19-9 and CEA levels may indicate stage of the disease, but neither has an independent prognostic value.     

术前炎症相关指标与可切除胃癌患者预后的相关性

目的 探讨术前外周血系统性免疫炎症指数(Systemic immune-inflammation index,SII)、中性粒细胞与淋巴细胞比值(Neutrophil to lymphocyte ratio,NLR)、血小板与淋巴细胞比值(Platelet to lymphocyte radio,PLR)与可切除胃癌患者预后的相关性及其临床意义。方法 回顾性分析2013年10月—2015年2月哈尔滨医科大学附属肿瘤医院收治的226例经手术治疗胃癌患者的临床病理资料。评估并比较SII、NLR、PLR在可切除胃癌患者中的预后价值。结果 胃癌组SII、NLR、PLR显著高于健康对照组,差异均有统计学意义(P＜0.05)。多因素Cox回归分析结果显示SII高(HR=2.947,95% CI:1.345~6.454,P=0.007)、NLR高(HR=2.876,95% CI:1.445~5.724,P=0.003)、T分期越高(HR=5.885,95% CI:1.641~21.099,P=0.007)、有远处转移(HR=3.010,95% CI:1.472~6.154,P=0.003)是影响可切除胃癌患者预后的独立危险因素。SII预测可切除胃癌患者结局的ROC曲线下面积为0.840,灵敏度为86.6%,特异度为68.0%,高于NLR、PLR及CA199,且差异有统计学意义(P＜0.05)。结论 SII对可切除胃癌患者生存结局的评估价值优于NLR和PLR。     

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.     

Refraining from resection in patients with potentially curable gastric carcinoma

BackgroundSurgical resection is the cornerstone of curative treatment for gastric cancer. The aim of this study was to evaluate reasons for and patient- and tumor characteristics that are associated with refraining from surgical resection in patients with potentially curable gastric cancer.Materials and methodsBetween 2015 and 2017, all patients with potentially curable gastric adenocarcinoma (cT1-4a-x, cN0-3-x, cM0) were included from the Netherlands Cancer Registry (NCR). Patients were divided into a resection (RG) and a no-resection group (nRG). Reasons for not undergoing resection as registered by the NCR were evaluated. Using multivariable logistic regression analyses, patient and tumor characteristics associated with refraining from resection were assessed.ResultsOf the 1679 analyzed patients with potentially curable disease, 1127 patients (67%) underwent resection, and 552 patients (33%) did not. Most common registered reasons for refraining from surgery were patient refusal (25%), low performance status (23%), comorbidity and extent of disease (both 10%). Factors associated with not undergoing resection were: age ≥80 years (OR 4.77, [95%CI 2.27–10.06], p < 0.001), low Social-Economic-Status (SES) (OR 2.68 [95%CI 1.31–5.46], p = 0.007), WHO performance status 3–4 (OR 10.48 [95%CI 2.41–45.73], p = 0.002) with several accompanying comorbidities, unclassified Lauren classification (OR 3.93 [95%CI 1.61–9.56], p = 0.003) and overlapping/diffuse tumors (OR 3.51, [95%CI 1.54–8.05], p = 0.003).ConclusionA third of patients with potentially curable gastric cancer did not undergo resection. Most frequent registered reasons for refraining from surgery were patient refusal, performance status, comorbidity and extent of disease. Additionally, multivariable analyses identified higher age, lower SES, and poor tumor characteristics as associated factors.     

A phase I trial of preoperative radiotherapy and capecitabine for locally advanced, potentially resectable rectal cancer

The purpose of the study was to determine the maximum-tolerated dose (MTD) of oral capecitabine, combined with concurrent, standard preoperative pelvic radiotherapy, when given twice daily, from Monday to Friday throughout the course of radiotherapy, for locally advanced potentially resectable rectal cancer. Maximum-tolerated dose was defined as the total (given in two equally divided doses) oral dose of capecitabine that caused treatment-related grade 3 or 4 toxicity in one-third or more of the patients treated. Radiotherapy involved 50.4 Gy given in 28 fractions in 5 weeks and 3 days. Eligible patients had a newly diagnosed clinical stage T3-4 N0-2 M0 rectal adenocarcinoma located within 12 cm of the anal verge suitable for curative resection. Surgery was performed 4-6 weeks from completion of preoperative chemoradiotherapy. In all, 28 patients were enrolled in the study at predefined dose levels: 850 mg m(-2) day(-1) (n=3), 1000 mg m(-2) day(-1) (n=6), 1250 mg m(-2) day(-1) (n=3), 1650 mg m(-2) day(-1) (n=3), 1800 mg m(-2) day(-1) (n=8) and 2000 mg m(-2) day(-1) (n=5). The mean age was 62.3 years (range: 33-80 years). Five patients were female and 23 male. The median distance of tumour from the anal verge was 6 cm (range: 1-11 cm). Endorectal ultrasound was performed in 93% of patients. A total of 26 patients (93%) had T3 disease and two patients had resectable T4 disease. Dose-limiting toxicity (DLT) developed in one patient at dose level 1000 mg m(-2) day(-1) (RTOG grade 3 cystitis). Two of the five patients at dose level 2000 mg m(-2) day(-1) had a total of three DLT (grade 3 perineal skin reaction, grade 3 diarrhoea and grade 3 dehydration). Dose escalation of capecitabine was ceased at 2000 mg m(-2) day(-1) after reaching MTD. None of the eight patients at dose level 1800 mg m(-2) day(-1) developed DLT. All except one patient underwent surgery. A total of 15 patients had the clinical T stage reduced by at least one stage in pathologic specimens. Five patients (19%) achieved a pathologic complete response. We conclude that the MTD of capecitabine was reached at a dose level of 2000 mg m(-2) day(-1), given as 1000 mg m(-2) twice daily, from Monday to Friday throughout the course of preoperative pelvic irradiation of 50.4 Gy. For patients with resectable rectal cancer receiving concurrent, full dose radiotherapy, the recommended dose of capecitabine for further study is 1800 mg m(-2) day(-1) when given in this schedule.     

Usefulness of magnetic resonance volumetric evaluation in predicting response to preoperative concurrent chemoradiotherapy in patients with resectable rectal cancer

PURPOSE: We performed magnetic resonance (MR) volumetry before and after neoadjuvant chemoradiation for evaluating response to therapy in T3 and T4 rectal cancer. To investigate the utility of MR volumetry for predicting the response to neoadjuvant chemoradiation, we compared results from MR volumetry before chemoradiation with those after chemoradiation. METHODS AND MATERIALS: A total 112 patients with T3 or T4 rectal cancer who successfully underwent MR volumetry and completed neoadjuvant chemoradiation followed by radical resection for cure were identified. MR volumetries were performed before and after chemoradiation. We compared pre- and postchemoradiation tumor volume and % volume reduction rates of patients whose tumors were down-staged with those of patients that were not down-staged. The same analyses were also performed between those patients having a complete histologic regression and those with residual disease in the operative specimen. We assessed the difference of % volume reduction rate according to Dworak's rectal cancer regression grades. RESULTS: Fifty-seven patients (50.9%) demonstrated a tumor down-staging after chemoradiation therapy. Both pre- and posttreatment MR tumor volumes were significantly less in patients whose tumors were down-staged than in patients that were not down-staged (p = 0.04, 0.031), and % volume reduction rates were significantly higher in patients whose tumors were down-staged (p = 0.024). Sixteen patients (14.3%) showed pathologically complete tumor regression. The differences of MR tumor volumes before and after chemoradiation and % volume reduction rates were not significantly different between patients having a complete histologic regression and those with residual disease (p = 0.688, 0.451, and 0.480). The differences of % volume reduction rates according to Dworak's grades were statistically significant (p = 0.03). CONCLUSION: The MR volumetric examinations before and after chemoradiation demonstrated the significant difference of tumor volume and % volume reduction rate between patients whose tumors were down-staged and those that were not down-staged. The volume reduction rates were significantly different among groups according to Dworak's grades. However, the MR volumetric evaluation could not identify any differences between those patients having a complete histologic regression and those with residual disease.     

The role of chemoradiation for patients with resectable or potentially resectable pancreatic cancer

Conflicting data and substantial controversy exist regarding optimal adjuvant treatment for those patients with resectable or potentially resectable adenocarcinoma of the pancreas. Despite improvements in short-term surgical outcomes, the use of newer chemotherapeutic agents, development of targeted agents and more precise delivery of radiation, the 5-year survival rates for early-stage patients remains less than 25%. This article critically reviews the existing data for various adjuvant treatment approaches for patients with surgically resectable pancreatic cancer. Our review confirms that despite several randomized clinical trials, the optimal adjuvant treatment approach for these patients remains unclear.     

Evaluation of chest computed tomography in the staging of patients with potentially resectable liver metastases from colorectal carcinoma.

BACKGROUND: Chest computed tomography (CT) often is used to rule out lung metastases in patients with potentially resectable liver metastases from colorectal carcinoma. In the current study the authors evaluated whether CT of the chest was necessary in patients with a negative chest radiograph. METHODS: The authors performed a retrospective analysis of 202 patients with negative initial chest X-rays who were undergoing evaluation for potentially resectable liver metastases from colorectal carcinoma. Patients with highly suspicious pulmonary lesions on the initial chest CT scan underwent a thoracoscopy and biopsy. All patients were monitored for the development of pulmonary metastases. RESULTS: Sixty patients (30%) had a positive initial chest CT scan. Two patients were found to have metastases by comparison with prior CT scans. Seventeen patients had highly suspicious lesions that were biopsied, but only 2 were found to have pulmonary metastases; the other lesions were benign. An additional 13 of these 60 patients developed lung metastases during follow-up, 6 of whom were diagnosed in retrospect. Of the 142 patients with a negative initial CT scan, 33 (23%) developed pulmonary metastases. The rate of pulmonary metastases in both groups was not significantly different, regardless of whether the CT scans were positive or negative. CONCLUSIONS: During routine preoperative workup for liver resection, the majority of lesions appearing on chest CT scans of patients with negative chest radiographs were not malignant. The positive yield of CT-guided workup was only 10 of 202 patients (5%). Based on this review the authors question the use of chest CT scans in this setting.     

Multi-institutional analysis of cervical esophageal carcinoma patients treated with definitive chemoradiotherapy: TROD 01-005 study

The aim of this study was to examine the prognostic factors and treatment outcomes of cervical esophageal carcinoma (CEC) patients who underwent definitive chemoradiotherapy (CRT). The clinical data of 175 biopsy-confirmed CEC patients treated with definitive CRT between April 2005 and September 2021 were retrospectively analyzed. The prognostic factors predicting overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were assessed in uni- and multivariable analyses. The median age of the entire cohort was 56 years (range: 26–87 years). All patients received definitive radiotherapy with a median total dose of 60 Gy, and 52% of the patients received cisplatin-based concurrent chemotherapy. The 2-year OS, PFS, and LRFS rates were 58.8%, 46.9%, and 52.4%, respectively, with a median follow-up duration of 41.6 months. Patients’ performance status, clinical nodal stage, tumor size, and treatment response were significant prognostic factors for OS, PFS, and LRFS in univariate analysis. Non-complete treatment response was an independent predictor for poor OS (HR = 4.41, 95% CI, 2.78–7.00, p < 0.001) and PFS (HR = 4.28, 95% CI, 2.79–6.58, p < 0.001), whereas poor performance score was a predictor for worse LRFS (HR = 1.83, 95% CI, 1.12–2.98, p = 0.02) in multivariable analysis. Fifty-two patients (29.7%) experienced grade II or higher toxicity. In this multicenter study, we demonstrated that definitive CRT is a safe and effective treatment for patients with CEC. Higher radiation doses were found to have no effect on treatment outcomes, but a better response to treatment and a better patient performance status did.     

65例可切除老年胃癌临床病理特征和预后分析

目的:分析65例可切除老年胃癌患者的临床病理特征和预后。方法:回顾性分析病理证实的65例年龄≥65岁老年可切除胃癌患者的临床病理特征和预后。60例(92.3%)患者行R0切除。62例(95.4%)患者行D2术。18例(27.7%)患者行术后辅助化疗。Kaplan-Meier法分析生存率,Log-rank检验比较组间生存差异。结果:65例患者中,男49例,女16例。60例(92.3%)患者为腺癌。TNM分期为I-II和III期患者分别为15例(23.1%)和50例(76.9%)。32例(49.2%)患者伴有合并症,6例(9.2%)伴有1个以上合并症。全组患者2年总生存率(overall survival,OS)、无进展生存率(progression-free survival,PFS)和癌症特异生存率(cancer-specific survival,CSS)分别为42.6%、28.4%和49.0%。单因素分析发现,N0-1患者的预后明显优于N2-3的患者,2年OS、PFS和CSS分别为77.9%和31.6%(P=0.010)、78.6%和16.3%(P=0.002)以及83.1%和37.3%(P=0.023)。死亡原因分析发现,33例死亡患者中,肿瘤相关死亡25例(75.8%),治疗相关或合并症相关死亡8例(24.2%)。结论:可切除老年胃癌的合并症多见,治疗相关或合并症相关死亡多见,N分期是最重要的临床预后因素。     

Concentrated preoperative radiotherapy for resectable gastric cancer: 20-years follow-up of a randomized trial

BACKGROUND AND OBJECTIVES: The role of radiation therapy in resectable gastric cancer is questionable. To study the value of concentrated preoperative radiotherapy, a randomized clinical trial had been carried out. METHODS: From 1974 to 1978, 152 patients were randomized and underwent exploratory laparotomy; in 50 patients curative surgery was not possible, while 102 patients satisfied protocol requirements and entered in the trial. Patients in the experimental group were treated with preoperative radiotherapy (20 Gy/5 days) and subtotal or total gastrectomy. Patients in the control group underwent surgery alone. RESULTS: Study showed acceptable tolerance of radiotherapy regime with no increase of postoperative mortality and morbidity. There was no significant difference in survival between the two treatment groups (chi 2 = 0.349, df = 1, P = 0.555). Subset analysis also failed to demonstrate significant survival advantages of the combined treatment; however, some positive trends were seen in patients with locally advanced gastric cancer. CONCLUSIONS: Concentrated preoperative radiotherapy in the dose of 20 Gy is safe and feasible, but seems to be insufficient to improve survival in gastric cancer patients. However, the results are promising in selected subgroups of patients, which encourages future trials with adjuvant radiation therapy.     

潜在可切除胃癌新辅助化疗的临床疗效观察

目的探讨潜在可切除胃癌新辅助化疗的临床疗效。方法收集本科收治的进展期及局部晚期潜在可切除胃癌患者31例，予以改良DCF方案（mDCF）化疗2～4个周期，观察其临床疗效及不良反应。结果全组获CR1例，PR15例，SD10例，PD5例，临床有效率为51．61％，疾病控制率为83．86％。手术切除率为64．52％（20／31），其中R0切除率为45．16％（14／31），R1切除率为12．90％（4／31），R2切除率为6．45％（2／31）。姑息性手术7例（22．58％）。2例术后出现并发症，并发症发生率为10％（2／20）。主要不良反应为骨髓抑制、恶心呕吐及轻度肝功能损害，经对症处理后均可缓解及恢复。结论改良DCF方案应用于潜在可切除胃癌的新辅助化疗的临床疗效较好，该疗法可使肿瘤降期，增加手术切除的机会，化疗相关不良反应可耐受，安全性较高。     

Multicenter phase II trial of preoperative chemoradiotherapy with S-1 for locally advanced oral squamous cell carcinoma

Purpose

We evaluated whether preoperative chemotherapy with S-1 and concurrent radiotherapy is feasible and efficacious in the treatment of advanced oral squamous cell carcinoma.

Methods

Participants comprised 39 patients with oral carcinoma (stage III, n = 15; stage IVA, n = 24). All patients received a total radiation dose of 40 Gy, in once-daily 2-Gy fractions, and received S-1 at 65 mg/m²/day for 5 consecutive days, over 4 consecutive weeks with concurrent radiotherapy.

Results

Hematological toxicity was mild and reversible. The most common non-hematological toxicity was grade 3 mucositis, but this was transient and tolerable. Radical surgery was performed for 37 patients, with the remaining 2 patients declining the surgery. Postoperatively, local failure developed in 1 patient, and neck failure in 2 patients. Distant metastases were identified in 4 patients. At a median follow-up of 38.0 months (range 23–88 months), locoregional control, disease-specific survival, and overall survival rates at 3 years were 91.5, 83.8, and 83.8 %, respectively.

Conclusion

Concurrent administration of S-1 and radiotherapy combined with surgery offers a well-tolerated method of successfully treating advanced oral squamous cell carcinoma. The locoregional control rate remains high even at 3 years of follow-up, and no serious adverse effects have been encountered.     

Complete response of a highly advanced gastric carcinoma to preoperative chemoradiotherapy with S-1 and low-dose cisplatin

S-1 has been developed as a new oral anticancer drug, based on the biological modulation of 5-fluorouracil. We report a patient with highly advanced gastric carcinoma who was treated successfully with a new combination chemoradiotherapy using S-1 and cisplatin (CDDP). The patient was a 37-year-old man who was diagnosed with advanced gastric carcinoma (T4N3M0) that had invaded the diaphragm and the paraaortic tissues. Remarkable tumor reduction was observed in the primary tumor and metastatic lymph nodes around the stomach after three cycles of the therapy. Radiological examination before surgery determined that a partial response (PR) had been achieved by the initial therapy. Adverse effects included only a gastrointestinal disorder that was limited to grade 2 when low-dose CDDP was utilized in the regimen, while an initial high dose of CDDP resulted in grade 3 toxicity, due to myelosuppression. The patient underwent curative surgery, including total gastrectomy, D2 lymph node dissection, and splenectomy, after completion of the radiochemotherapy regimen. No surgical complication was observed. No tumor cells were detected by pathological evaluation of the resected stomach and all the regional lymph nodes, confirming a pathological complete response (CR; grade 3). This regimen is a potent treatment for advanced gastric carcinoma, especially when used as preoperative chemotherapy to control cancer cells.     

Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma.

PURPOSE: A pilot study of 43 patients with potentially resectable esophageal carcinoma treated with an intensive regimen of preoperative chemoradiation with cisplatin, fluorouracil, and vinblastine before surgery showed a median survival of 29 months in comparison with the 12-month median survival of 100 historical controls treated with surgery alone at the same institution. We designed a randomized trial to compare survival for patients treated with this preoperative chemoradiation regimen versus surgery alone. MATERIALS AND METHODS: One hundred patients with esophageal carcinoma were randomized to receive either surgery alone (arm I) or preoperative chemoradiation (arm II) with cisplatin 20 mg/m2/d on days 1 through 5 and 17 through 21, fluorouracil 300 mg/m2/d on days 1 through 21, and vinblastine 1 mg/m2/d on days 1 through 4 and 17 through 20. Radiotherapy consisted of 1.5-Gy fractions twice daily, Monday through Friday over 21 days, to a total dose of 45 Gy. Transhiatal esophagectomy with a cervical esophagogastric anastomosis was performed on approximately day 42. RESULTS: At median follow-up of 8.2 years, there is no significant difference in survival between the treatment arms. Median survival is 17.6 months in arm I and 16.9 months in arm II. Survival at 3 years was 16% in arm I and 30% in arm II (P = .15). This study was statistically powered to detect a relatively large increase in median survival from 1 year to 2.2 years, with at least 80% power. CONCLUSION: This randomized trial of preoperative chemoradiation versus surgery alone for patients with potentially resectable esophageal carcinoma did not demonstrate a statistically significant survival difference.     

Acute respiratory disease syndrome with preoperative chronomodulated chemoradiotherapy in patients with esophageal cancer. Early termination of a phase I trial

A phase I trial was initiated to establish the dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of chronomodulated 5-fluorouracil and cisplatin given concurrently with preoperative radiotherapy in patients with esophageal cancer. Patients with stage I or II esophageal cancer received preoperative radiation therapy (28–30 daily 1.8-Gy fractions for a total of 50.4 or 54 Gy) and concurrent three fortnightly cycles of chronomodulated 5-fluorouracil (700–835 mg/m² per day, d1–d4, with peak delivery at 4.00 am) and cisplatin (50 mg/m², d1, with peak delivery at 4.00 pm) administered by a time-programmable pump. Ten patients were treated on this study. Two of six patients treated at the starting dose-level experienced acute DLTs (esophagitis, asthenia) which required de-escalation of 5-fluorouracil. Five patients out of ten experienced seven DLTs (severe esophagitis, asthenia, vomiting: 5/1/1) at any dose-level. The MTD was not assessed because the study was halted due to slow accrual. Finally, two patients deceased from an Acute Respiratory Distress Syndrome due to inadequate radiation therapy planning. Without definitively ruling out any possible impact of chronomodulation in that setting, our data reinforce the need of a better selection of patients aimed to be treated by CRT plus surgery.