Differences in toxicity across gender in patients treated with chemoradiation for rectal cancer

The primary objective was to prospectively investigate the efficacy and toxicity of bolus 5‐fluorouracil (5‐FU) chemotherapy compared with the infusional 5‐FU in combination with preoperative radiation in patients with locally advanced rectal cancer. Furthermore, in light of previous reports, toxicity profiles between men and women were also compared. Eighty‐four consecutive patients with rectal adenocarcinoma were prospectively treated. There were no differences in tumour response, local recurrence or survival between bolus versus infusional groups or gender groups. In locally advanced rectal cancer, preoperative infusional chemotherapy combined with radiation was found to be less toxic than bolus chemotherapy and radiotherapy. Both regimens produced more toxic effects in women compared with men.     

A case of rectal cancer treated by preoperative chemoradiation

Fifty-one-year-old male visited our hospital suffering from anal pain and subileus. Further examination revealed that advanced rectal cancer which invaded to presacral space (Ai, N 0, P 0, H 0, M(-), stage IIIa) caused such symptom. We administered neo-adjuvant chemoradiotherapy for fear of non curative resection of the rectum. The regimen was once weekly administration of intravenous CPT-11 40 mg, plus daily oral administration of UFT-E 600 mg/day and Uzel 75 mg/day for 4 weeks. In addition we underwent radiation 2.4 Gy/day and intravenous low-dose cisplatin (CDDP) 5 mg/day, 5 days/week for 3 weeks. Four weeks after the first administration, a partial response was confirmed on CT, and so we carried out an abdominoperineal resection. The postoperative course is almost uneventful without a little perineal infection. The specimen revealed that no malignant lesion remained, which changed to necrotic tissue. The side effects were not so severe. For example, diarrhea, nausea, and mucosal dysfunction were each less than grade 2, and there was much tolerate for renal, liver, and bone marrow function. This combination chemoradiotherapy is considered to be effective for locally advanced rectal cancer.     

Prognostic factors in esophageal squamous cell carcinoma patients treated with neoadjuvant chemoradiation therapy

Background

Definitive evaluation of surgical specimens obtained after neoadjuvant chemoradiation therapy (CRT) is important for assessing additional treatment or prognosis in patients with esophageal squamous cell carcinoma (ESCC). In this study, we examined the histological prognostic factors for ESCC patients treated with CRT and determined an appropriate strategy for their evaluation.

Patients and methods

The present study involved 38 consecutive ESCC patients who underwent CRT followed by curative operation. CRT consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. We examined histological variables as follows: CRT effect on primary tumor (T-effect: T-effective/T-ineffective), tumor depth (pT), lymph node metastases (pN: pN0/N1), number of lymph node metastases (number-pN), lymphatic invasion, and venous invasion. Univariate and multivariate analyses were performed to examine the independent prognostic factors. Survivals and mode of recurrence were then evaluated according to the independent prognostic factors.

Results

In the univariate analyses, T-effect, pN, number-pN, lymphatic invasion, and venous invasion were found to be prognostic factors with p < 0.01, and pT was a factor with p < 0.05. In the multivariate analysis, pN and T-effect were independent prognostic factors. The five-year survival rate of pN0 patients was more than 75%, even though the T-effect was poor. The 5-year survival rate of patients judged as pN1/T-effective was 50%, whereas all of the pN1/T-ineffective patients died within 2 years with relapse disease.

Conclusion

The evaluation method using both pN status and T-effect is useful for assessing prognosis of ESCC patients treated with neoadjuvant CRT.     

食管癌患者放化疗前后代谢组学指标改变的观察

目的:检测并比较食管癌患者放化疗前后血浆代谢产物的含量差异,分析化疗前与化疗后食管癌代谢物的特异性的改变.方法:收集食管癌患者放化疗前后清晨空腹血液标本,共71例,采用核磁共振法测定血浆标本中代谢产物的含量,用正交偏最小二乘判别法(OPLS-DA)分析化疗前后血浆代谢产物含量差异及其临床意义.结果:放化疗后与放化疗前相比,血浆中乳酸盐、血肌酐、脂类、甘油酯、不饱和脂肪酸含量增加(P<0.05),甲酸、天冬氨酸、三甲胺、胆碱含量减少(P<0.05).结论:食管癌患者化疗前与化疗后血浆中代谢产物明显不同,基于核磁共振法的代谢组学可以很好的反映放化疗前后代谢产物的差异.     

Improved survival with adjuvant chemotherapy in locally advanced rectal cancer patients treated with preoperative chemoradiation regardless of pathologic response

ObjectiveThe aim of this study is to examine the effect of postoperative chemotherapy on survival in patients with stage II or III rectal adenocarcinoma who undergo neoadjuvant chemoradiation (CRT) and surgical resection.MethodsA retrospective review of the National Cancer Database (NCDB) from 2006 to 2013 was performed. Cases were analyzed based on pathologic complete response (pCR) status and use of adjuvant therapy. The Kaplan-Meier method was used to estimate overall survival probabilities.Results23,045 cases were identified, of which 5832 (25.31%) achieved pCR. In the pCR group, 1513 (25.9%) received adjuvant chemotherapy, and in the non-pCR group, 5966 (34.7%) received adjuvant therapy. In the pCR group, five-year survival probability was 87% (95% CI 84%–89%) with adjuvant therapy and 81% (95% CI 79%–82%) without adjuvant therapy. In the non-pCR group, five-year survival probability was 78% (95% CI 76%–79%) with adjuvant therapy and 70% (95% CI 69%–71%) without adjuvant therapy. In the non-pCR and node-negative subgroup (ypN-), five-year survival probability was 86% (95% CI 84%–88%) with adjuvant therapy and 76% (95% CI 74%–77%) without adjuvant therapy. In the non-pCR and node-positive subgroup (ypN+), five-year survival probability was 67% (95% CI 65%–70%) with adjuvant therapy and 60% (95% CI 58%–63%) without adjuvant therapy.ConclusionsAdjuvant chemotherapy in stage II or III rectal adenocarcinoma is associated with increased five-year survival probability regardless of pCR status. We observed similar survival outcomes among non-pCR ypN- treated with adjuvant chemotherapy compared with patients achieving pCR treated with adjuvant chemotherapy.     

Association of beclin 1 expression with response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal carcinoma

Beclin 1 is an essential regulator of autophagy that is induced in response to cellular stress and serves to maintain cell survival in established tumors. We recently demonstrated that Beclin 1 suppression can sensitize colorectal cancer cells to radiation‐induced DNA damage and apoptosis. Therefore, we hypothesized that the level of Beclin 1 expression may be associated with radiation sensitivity in vivo. We determined the association of Beclin 1 expression in pretreatment rectal cancer tissues with response to neoadjuvant chemoradiation in surgical resection specimens. Stages II and III (n = 96) rectal adenocarcinoma patients were treated with neoadjuvant chemoradiation followed by surgical resection with curative intent. Beclin 1 was analyzed by immunohistochemistry and the expression level was dichotomized at the median value with categorization into low and high groups. We identified 56 (58.3%) and 40 (41.7%) patients whose tumors had high‐ versus low‐level Beclin 1 expression, respectively. Rectal cancers with high versus low Beclin 1 expression were significantly less likely to be downstaged after chemoradiation treatment (45% [25/55] vs. 58% [22/38]; p = 0.02). In a multivariable analysis adjusted for age, sex, histological grade and baseline tumor node metastasis (TNM) stage, the impact of Beclin 1 expression on tumor downstaging remained statistically significant (p = 0.03). The association of the level of Beclin 1 expression with the rate of tumor downstaging after chemoradiation is consistent with in vitro data, and suggests that Beclin 1 may be a predictive biomarker for the efficacy of chemoradiation in patients with rectal cancer.     

Definitive chemoradiation in patients with inoperable oesophageal carcinoma

We performed a retrospective study of 90 consecutive cases with inoperable carcinoma of the oesophagus treated with definitive chemoradiation at a single cancer centre between 1995 and 2002. For the last 4 years, 73 patients have received therapy according to an agreed protocol. This outpatient-based regimen involves four cycles of chemotherapy, cycles 3 and 4 given concurrently with 50 Gy external beam radiotherapy (XRT) delivered in 25 fractions over 5 weeks. Cisplatin 60 mg m(-2) day(-1) is given every 3 weeks together with continuous infusional 5-fluorouracil 300 mg m(-2) day(-1), reduced to 225 mg m(-2) day(-1) during the XRT. In all, 45 (50%) patients suffered one or more WHO grade 3/4 toxicity, grade 3 in 93% cases. Patients received more than 90% of the planned chemoradiation schedule. The median overall survival was 26 (15, >96) months, 51% (41, 64) and 26% (13, 52) surviving 2 and 5 years, respectively. Advanced stage, particularly T4 disease, was associated with a worse prognosis. Patients considered not suitable for surgery for reasons other than their disease, mainly co-morbidity, had a significantly better outcome, median survival 40 (26, >96) months, 2- and 5-year survivals 67% (54, 84) and 32% (13, 79), respectively (P<0.001). This schedule is a feasible, tolerable and effective treatment for patients with oesophageal cancer considered unsuitable for surgery.     

Salivary gland carcinoma treated with concomitant chemoradiation with intraarterial cisplatin and docetaxel

Malignant neoplasms of the salivary gland are uncommon entities in which surgical resection of the primary lesion has been accepted as a standard therapeutic option. The efficacy of radiation and systemic chemotherapy has been limited for patients with recurrent, metastatic, or unresectable disease because of unfavorable response rates and the short duration of the response. We treated one patient with recurrent adenoid cystic carcinoma arising from the sublingual gland and one patient with primary adenocarcinoma arising from the parotid gland with transfemoral intraarterial chemotherapy, based on full-dose cisplatin and docetaxel and concurrent external-beam radiotherapy. The doses of cisplatin and docetaxel in the two patients were 80–100 mg/m² and 10–15 mg/m², respectively. Docetaxel was infused first, followed by cisplatin. Both patients obtained complete responses. Although complications such as mucositis, anorexia, neutropenia, and ischemic colitis were observed, they were well tolerated and manageable. The concomitant chemoradiotherapy of cisplatin and docetaxel seemed to be a practicable option for patients with recurrent and unresectable salivary gland carcinomas.     

18F-FDG positron emission tomography staging and restaging in rectal cancer treated with preoperative chemoradiation

PURPOSE: To assess the information supplied by FDG-PET in patients with locally advanced rectal cancer both in the initial staging and in the evaluation of tumor changes induced by preoperative chemoradiation (restaging). METHODS AND MATERIALS: Twenty-five consecutive patients with rectal cancer were included, with tumor stages (c)T(2-4)N(x)M(0), during the period 1997-1999. We prospectively performed two FDG-PET scans in all patients to assess disease stage (1) at initial diagnosis and (2) presurgically, 4 to 5 weeks after protracted chemoradiation. Protracted chemoradiation was carried out during 5-6 weeks with 45-50 Gy, plus concurrent oral tegafur 1200 mg/day or 5-fluorouracil 500-1000 mg/m(2) administered as a 24-h continuous i.v. infusion on Days 1-4 and 21-25 of the radiotherapy treatment. Tumors were staged with CT in 95% of patients, whereas endorectal ultrasound was used in 90% of patients. Maximum standardized uptake value (SUVmax) was used as the quantitative parameter to estimate the tumor:tissue metabolic ratio. RESULTS: Preoperative chemoradiation significantly decreased the SUVMAX: 5.9 (mean SUVmax at initial staging) vs. 2.4 (mean SUVmax after chemoradiation) with p < 0.001. Unknown liver metastases were detected by FDG-PET in 2 patients, in 1 of them with the initial staging FDG-PET scan, and with the restaging FDG-PET scan in the other. After an average follow-up of 39 months, the value of SUVmax > or =6 allowed us to discriminate for survival at 3 years: 92% vs. 60% (p = 0.04). T downstaging (total 62%) was significantly correlated with SUVmax changes: 1.9 vs. 3.3 (p = 0.03). The degree of rectal cancer response to chemoradiation, established as mic vs. mac categories, was not associated with SUVmax differences (mean values of 2.0 vs. 2.7). CONCLUSION: Preliminary results observed suggest the potential utility of FDG-PET as a complementary diagnostic procedure in the initial clinical evaluation (8% of unsuspected liver metastases) as well as in the assessment of chemoradiation response (any T downstaged event) of locally advanced rectal cancer. Initial SUVmax might be of prognostic value related to long-term patient outcome.     

同步放化疗对早期低危宫颈鳞癌术后生存无优势

  目的  探讨早期宫颈鳞癌术后伴有低危复发因素患者减少不良反应的最佳处理方式。  方法  选取2008年2月至2012年3月山东省肿瘤医院共收治经术后病理证实, 伴有1~2个低危不良预后因素的早期宫颈鳞癌患者133例。根据术后治疗方式不同分为单纯放疗组(42例)、化疗+后装治疗组(47例)和同步放化疗组(44例), 比较3组患者的无疾病生存率和治疗相关并发症发生率。  结果  随访时间为6~55个月, 中位随访时间30个月。单纯放疗组、化疗+后装治疗组和同步放化疗组3年无疾病生存率分别为94.0%、93.4%和97.6%, 差异无统计学意义(P>0.05)。3组急性重度不良反应(Ⅲ~Ⅳ级)发生率分别为9.5%、16.7%和34.1%, 同步放化疗组Ⅲ~Ⅳ级不良反应发生率显著高于单纯放疗组和化疗+后装治疗组(P < 0.05), 而单纯放疗组与化疗+后装治疗组之间差异无统计学意义(P>0.05)。3组Ⅰ~Ⅱ度慢性放射性反应发生率分别为19.0%、4.3%和25.0%, 单纯放疗组和同步放化疗组显著高于化疗+后装治疗组(P < 0.05), 单纯放疗组与同步放化疗组比较差异无统计学意义(P>0.05)。  结论  对于早期低危宫颈鳞癌患者, 与同步放化疗相比, 术后采用化疗+后装治疗或单纯放疗均能够取得理想的治疗效果, 而治疗相关并发症发生率明显降低。      

Response to preoperative chemoradiation increases the use of sphincter-preserving surgery in patients with locally advanced low rectal carcinoma

BACKGROUND: Although controversial, some believe that preoperative chemoradiation increases the use of sphincter-preserving surgery in low rectal carcinoma patients. This article investigates the relationship between objective tumor response and sphincter preservation in low rectal carcinoma patients. METHODS: The authors reviewed the records of 238 patients with T3 or T4 low rectal carcinoma (< or = 6 cm from the anal verge) who underwent preoperative pelvic chemoradiation (45 Gy/25 fractions/5 weeks, n = 182 or 52.5 Gy/30 fractions/5 weeks, n = 56 with continuous infusion 5-fluorouracil at 300 mg/m(2), Monday to Friday) followed by mesorectal (n = 223) or local excision (n = 15). A logistic regression analysis was used to analyze the influence of objective tumor response (defined as complete clinical response) and other prognostic factors on sphincter preservation. Because degrees of partial response could not be objectively defined retrospectively, the influence of partial response on sphincter preservation could not be evaluated. RESULTS: Overall, 49% of patients (117 of 238) had sphincter-preserving surgery. The clinical complete response rate was 47%. Independent predictors of sphincter preservation included the year of surgery, tumor distance from the anal verge, circumferential tumor involvement, and response to chemoradiation. The sphincter preservation rate increased over the period of the study (from 28% [December 1989 to December 1992] to 44% [January 1993 to December 1996] to 67% [January 1997 to December 2000]). The difference in the rates of sphincter preservation according to response was most striking among patients with tumors 3 cm or less from the anal verge (44% vs. 22%, P = 0.01). The pelvic disease recurrence rate among patients undergoing sphincter-preserving surgery has been less than 10% since January 1993 and was not statistically different between the groups treated from January 1993 to December 1996 and from January 1997 to December 2000. CONCLUSIONS: There has been an increase in the use of sphincter-preserving surgery without an increase in pelvic disease recurrence over the past decade. Although not necessary for sphincter preservation, clinical response to preoperative chemoradiation independently contributed to sphincter-preserving surgery, particularly in patients with low rectal tumors.     

Failure patterns in patients with esophageal cancer treated with definitive chemoradiation

BACKGROUND:

Local failure after definitive chemoradiation therapy for unresectable esophageal cancer remains problematic. Little is known about the failure pattern based on modern‐day radiation treatment volumes. We hypothesized that most local failures would be within the gross tumor volume (GTV), where the bulk of the tumor burden resides.

METHODS:

We reviewed treatment volumes for 239 patients who underwent definitive chemoradiation therapy and compared this information with failure patterns on follow‐up positron emission tomography (PET). Failures were categorized as within the GTV, the larger clinical target volume (CTV, which encompasses microscopic disease), or the still larger planning target volume (PTV, which encompasses setup variability) or outside the radiation field.

RESULTS:

At a median follow‐up time of 52.6 months (95% confidence interval, 46.1‐56.7 months), 119 patients (50%) had experienced local failure, 114 (48%) had distant failure, and 74 (31%) had no evidence of failure. Of all local failures, 107 (90%) were within the GTV, 27 (23%) were within the CTV, and 14 (12%) were within in the PTV. On multivariate analysis, GTV failure was associated with tumor status (T3/T4 vs T1/T2; odds ratio, 6.35; P = .002), change in standardized uptake value on PET before and after treatment (decrease >52%: odds ratio, 0.368; P = .003), and tumor size (>8 cm, 4.08; P = .009).

CONCLUSIONS:

Most local failures after definitive chemoradiation for unresectable esophageal cancer occur in the GTV. Future therapeutic strategies should focus on enhancing local control. Cancer 2011;. © 2011 American Cancer Society.     

Tumour regression grading in patients with residual rectal cancer after preoperative chemoradiation

Background and purpose

To explore the utility of tumour regression grading (TRG, the amount of residual tumour cells in relation to extension of fibrosis) after chemoradiation of rectal cancer.

Materials and methods

Of 131 patients who received preoperative chemoradiation in the frame of the randomized trial, pathological complete response (pCR, TRG0), good regression (TRG1), moderate regression (TRG2), and poor regression (TRG3) were recorded in 17%, 31%, 31%, and 22% of patients, respectively.

Results

The rates of ypN-positive category for TRG0, TRG1, TRG2, and TRG3 groups were 5%, 23%, 45%, and 46%, respectively, p = 0.001. When ypT-category and TRG were evaluated by the logistic regression analysis, only ypT-category remained significant for independent prediction of the risk for mesorectal nodal metastases, p = 0.006. The 4-year (median follow-up) disease-free survival (DFS) for TRG0, TRG1, TRG2, and TRG3 groups were 91%, 67%, 54%, and 47%. When patients with persistent disease (TRG1 vs. TRG2 vs. TRG3) were analyzed separately, TRG had no prognostic value for DFS, p = 0.402.

Conclusions

TRG in patients with residual cancer had no prognostic value for the incidence of nodal disease and for DFS. Our findings and literature data question the need for the inclusion of TRG assessment into a routine pathological report.     

Altered tryptophan and neopterin metabolism in cancer patients treated with recombinant interleukin 2

Immune stimulation or interferon administration induces indoleamine 2,3-dioxygenase and GTP cyclohydrolase activity in humans, resulting, respectively, in tryptophan degradation to kynurenine and in neopterin production. To determine if similar effects result from interleukin 2 (IL-2) administration, plasma tryptophan and urinary kynurenine and neopterin were measured in patients undergoing a phase 1 toxicity trial of recombinant IL-2 given by daily bolus or continuous i.v. administration for 7 days at doses of 1 x 10(5) to 1 x 10(7) units/m2/day. Significant dose-dependent decreases in plasma tryptophan levels and corresponding increases in urinary kynurenine and neopterin were observed. These metabolic effects of IL-2 are probably mediated by induction of gamma-interferon production, although elevated levels of gamma-interferon were not found in the sera of these patients. In view of the indispensable role of tryptophan in synthesis of protein, niacin, and serotonin, we suggest that some of the toxic side effects may be the result of this loss of tryptophan. Since these metabolic changes were detected at relatively low doses of IL-2, these assays provide a highly sensitive means for monitoring in vivo metabolic responses to IL-2 therapy.     

A case of advanced esophageal carcinoma successfully treated with chemoradiation therapy with low-dose cisplatin and 5-fluorouracil

We have experienced a case of advanced esophageal carcinoma successfully treated with chemoradiation therapy together with low-dose cisplatin and 5-fluorouracil, having only minor toxicity. A 55-year-old man was admitted to our hospital because of dysphagia. Cervical esophageal carcinoma was found to have invaded the larynx through endoscopy, and invasion to thyroid gland and trachea was suspected from a cervical CT. We diagnosed the condition as advanced esophageal carcinoma (A2N(-)M0Pl0 Stage III). We then treated the patient by chemoradiation therapy. After the treatment, the carcinoma could not be detected by CT and endoscopy, and endoscopic biopsy revealed there were no active carcinoma cells. The side effects of the therapy were very mild, therefore the patient could be discharged after a short time. No evidence of a tumor relapse was found 5 months after the therapy. We treated 4 patients with esophageal carcinoma using the same regimen, and the results of the therapy were 2 CR, 1 PR, and 1 PD, with an overall response rate of 75%.