Volumetric modulated arctherapy for locally advanced nasopharyngeal carcinoma: Clinical efficacy and late toxicity

PurposeWe report our experience of 86 consecutive patients with locally advanced nasopharyngeal carcinoma who were treated with volumetric modulated arc therapy.Materials and methodsWe retrospectively reviewed the medical records of 86 patients with histologically proven primary nasopharyngeal carcinoma treated with volumetric modulated arctherapy technique radiotherapy. Primary endpoints were local, regional, distant control, and overall survival, second endpoint was late toxicity.ResultsThe median age was 47.5 years (range: 13–79 years) with sex ratio 1.09. At diagnosis, rhinologic symptoms represented the most common clinical presentation, reported by 61 patients (70.9%). Almost 88.4% of patients presented non-keratinizing undifferentiated carcinoma histology (n = 76). Most of the patients presented a locally advanced disease defined by stage III and IVa (95.3%). Therefore, 31 patients were treated by concurrent chemoradiation (36%), 52 patients received induction chemotherapy followed by concurrent chemoradiotherapy (57%), three patients received induction chemotherapy followed by exclusive radiotherapy (3.5%). and three patients treated with exclusive irradiation (3.5%). With a median follow up of 15.7 months (range: 4–33.3 months), nine patients died (10.4%), three presented local or locoregional relapse (3.4%), while nine patients presented distant recurrences (10.4%). The two years overall and disease-free survival rates were 88.7% and 83.1% respectively, locoregional control was 100% at 12 months and 96.2% at 24 months, and the two years distant failure-free survival was 86.7%. Time to relapse was the only prognostic factor in univariate analysis for overall survival in our study. The therapeutic tolerance was good with 61.7% of grade 3 and 2.3% grade 4 hyposialia respectively, 46.5% of otological disorders and no radionecrosis was noted.ConclusionVolumetric modulated arctherapy technique with concurrent chemoradiotherapy is an effective treatment for nasopharyngeal carcinoma with excellent overall and locoregional control without severe toxicity. Distant metastasis is the major site of failure, so induction chemotherapy added to chemoradiotherapy must be discussed in multidisciplinary consultation meeting because it significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone.     

Upfront chemotherapy and short-course radiotherapy with delayed surgery for locally advanced rectal cancer with synchronous liver metastases

BackgroundThe optimal treatment of locally advanced rectal cancer with synchronous liver metastases remains controversial. In this study, we aimed to evaluate the safety, efficacy, and oncologic outcomes of upfront chemotherapy and short-course radiotherapy with delayed surgery in patients with locally advanced rectal cancer and synchronous liver metastases.MethodsForty-four patients who underwent upfront chemotherapy and short-course radiotherapy with delayed surgery for locally advanced rectal cancer (cT3/4, <2.0 mm from the mesorectal fascia) with synchronous liver metastases between January 2010 and June 2017 were reviewed retrospectively. Primary and metastatic liver lesions were resected with curative intent. Upfront chemotherapy and short-course radiotherapy were administered. Thereafter, restaging, surgery only, or additional chemotherapy followed by surgery was performed.ResultsAt the time of initial diagnosis, 20 patients had <3 liver metastases; 24 patients had ≥3 liver metastases. Twenty-three patients had hemi-liver metastases; 21 patients had bilobar liver metastases. R0 resection of rectal lesions was achieved in 43 patients. Synchronous R0 resection of liver metastases was achieved in 41 patients. Postoperative complications (Clavien–Dindo Grade ≥ III) were noted in 5 patients. Grade 3/4 adverse events were observed in 26 patients. All adverse events were managed effectively with medication and supportive care. The 3-year overall survival and progression-free survival rates were 65.3% and 26.9%, respectively.ConclusionUpfront chemotherapy and short-course radiotherapy with delayed surgery appear to be safe and effective in patients with locally advanced rectal cancer and synchronous liver metastases without substantially increasing treatment induced morbidity.     

Palliative radiotherapy and chemotherapy instead of surgery in symptomatic rectal cancer with synchronous unresectable metastases: a phase II study

BackgroundIn stage IV rectal cancer, palliative surgery is often carried out upfront. This study investigated whether the surgery can be avoided.Patients and methodsForty patients with symptomatic primary rectal adenocarcinoma and synchronous distant metastases deemed to be unresectable received 5 × 5 Gy irradiation and then oxaliplatin-based chemotherapy. Before treatment, 38% of patients had a near-obstructing lesion. The palliative effect was evaluated by questionnaires completed by the patients.ResultsThe median follow-up for living patients was 26 months (range 19–34). The median overall survival was 11.5 months. Eight patients (20%) required surgery during the course of their disease: seven patients required stoma creation and one had local excision. Thirty percent of patients had a complete resolution of pelvic symptoms during the whole course of the disease, and 35% had significant improvement. In the subgroup with a near-obstructing lesion, 23% of patients required stoma creation. In all patients, the probability of requiring palliative surgery at 2 years was 17.5% [95% confidence interval (CI) 13% to 22%), and the probability of sustained good palliative effect after radiotherapy and chemotherapy was 67% (95% CI 58% to 76%).ConclusionShort-course radiotherapy and chemotherapy allowed most patients to avoid surgery, even those with a near-obstructing lesion.ClinicalTrialsThe trial is registered with ClinicalTrials.gov: number NCT01157806.     

Comment traiter un cancer du rectum avec métastases hépatiques synchrones ? Une question de stratégie thérapeutique

The prognosis of patients with rectal cancer and synchronous liver metastasis has improved thanks to chemotherapy and rectal and liver surgery progresses. However, there is no consensus about optimal management and practices remain heterogeneous. A curative treatment may be considered for 20 to 30% of patients with complete resection of metastasis and primary tumor after induction chemotherapy. To this end, a primary optimal evaluation by a multidisciplinary board including hepatic and colorectal surgeons is crucial. The therapeutic strategy associates chemotherapy, radiotherapy, hepatic and rectal surgery. The most threatening site guides the sequence of treatments. If hepatic resectability is uncertain, a “liver first” strategy associating induction chemotherapy and hepatic surgery is preferred. In non-resectable metastatic cases, chemotherapies with targeted therapies might lead to secondary resection for 30% of patients (conversion). This has changed our practice and triggers reconsidering resectability after chemotherapy. When metastases remain non-resectable, additional treatment focusing on primary tumor should control pelvic symptoms otherwise hardly impacting quality of life. Rectal surgery, short-course radiotherapy (5 × 5 Gy), conformational long-course chemoradiotherapy or intensity-modulated radiation therapy with dose escalation are options discussed in this review.     

241例局部晚期中低位直肠癌术前同步放化疗联合TME根治术长期疗效分析

目的 回顾性分析 241例局部晚期中低位直肠癌行术前同步放化疗联合TME根治性手术的长期疗效以及影响预后因素。方法 2006—2014年中国医学科学院北京协和医学院肿瘤国家癌症中心连续收治经盆腔MRI或腹盆CT确诊的局部晚期中低位直肠腺癌患者 241例进行分析,该组患者术前盆腔放疗剂量 42.0~50.4 Gy (中位数50 Gy),同步化疗采用卡培他滨 ±奥沙利铂,于同步放化疗后 4~15周(中位数7周)接受TME原则的根治性手术(R0切除),术后均建议行辅助化疗,但需考虑患者恢复情况及意愿。Kaplan-Meier法计算DFS、LRR、DM及OS并Logrank法检验,Cox模型多因素分析。结果 全组患者中位随访42个月,3年LRR、DFS、OS和DM分别为3.8%、76.2%、85.9%和20.6%。亚组分析发现ypT0-2、ypN阴性、pCR、TRG4级患者可以获得更高的DFS (ypT0-2∶ypT3-4:86.0%∶69.3%,P=0.002;ypN阴性∶ypN阳性:88.1%∶56.9%,P=0.000;pCR∶非pCR:100%∶72.4%,P=0.001;TRG4级∶TRG2-3级∶TGR0-1级:94.9%∶73.6%∶66.3%,P=0.011),多因素分析结果显示术后ypN状态是影响DFS的因素(P=0.000)。结论 局部晚期中低位直肠癌行术前同步放化疗联合根治性手术局部区域控制较理想,远处转移是治疗失败的主要原因,放化疗后ypN状态是影响DFS的独立预后因素。     

The reliability of lymph-node staging in rectal cancer after preoperative chemoradiotherapy

AimsTo determine the prognostic significance of the nodal stage and number of nodes recovered in the surgical specimen after preoperative synchronous chemoradiation (SCRT) and surgery for locally advanced or unresectable rectal cancer.Materials and MethodsOne hundred and eighty-two consecutive patients with locally advanced or unresectable (T3/T4) rectal carcinomas were entered on a prospective database and treated in this department with preoperative chemoradiation, followed 6–12 weeks later by surgical resection. Most patients received chemotherapy in the form of low-dose folinic acid and 5-fluorouracil (5-FU) 350 mg/m² via a 60-min infusion on days 1–5 and 29–33 of a course of pelvic radiotherapy delivered at a dose of 45 Gy in 25 fractions over 33 days to a planned volume. After resection, patients with a positive circumferential margin (≤1 mm), extranodal deposits or Dukes' C histology received adjuvant 5-FU-based-chemotherapy (n = 40).ResultsAfter SCRT, 161 patients underwent resection. Twenty-one patients remained unresectable or refused an exenterative operation. Median follow-up is 36 months. Down-staging was achieved in most patients, with 19 having a complete pathological response (pT0). The median number of lymph nodes recovered for all patients was five (range 0–21). The 3-year survival rate for node-positive patients is 47%, for node-negative patients with less than three lymph nodes recovered is 62% and for node-negative patients with three or more lymph nodes recovered is 70%. Compared with node-positive patients, simple regression models revealed a reduced hazard ratio (HR) of 0.72 (0.36–1.43) for node-negative patients with less than three nodes recovered and 0.48 (0.26–0.89) for node-negative patients with three or more lymph nodes recovered. In a multivariate model, including nodal status, excision status, age and sex only positive excision margins significantly predicted a poor outcome: HR = 3.05 (1.55–5.97).ConclusionsThe number of nodes found after preoperative chemoradiation is a significant prognostic factor by univariate analysis. In this study, patients with node-negative histology, and at least three nodes recovered, had better long-term survival than patients in whom two or less nodes were recovered or with positive nodes. This effect was attenuated by the inclusion of excision status in multivariate models.     

Is primary tumour resection associated with survival improvement in patients with colorectal cancer and unresectable synchronous metastases? A pooled analysis of individual data from four randomised trials

ObjectiveTo evaluate the impact on survival of primary tumour resection in patients with unresectable synchronous metastases from colorectal cancer (CRC).Summary background dataPrimary tumour resection in this setting remains controversial.Patients and methodsWe retrieved individual data of 1155 patients with metastatic CRC included in four first-line chemotherapy trials: Fédération Francophone de Cancérologie Digestive (FFCD)-9601, FFCD-2000-05, Actions Concertées dans les cancers COloRectaux et Digestifs (ACCORD)-13, and ML-16987. Patients with unresectable synchronous metastases were eligible for this study. We used univariate and multivariate analyses (Cox models stratified on the trial) to assess the impact of primary tumour resection and other potential prognostic variables on overall survival (OS) (the primary endpoint).ResultsAmongst the 1155 patients, 810 patients met the inclusion criteria and 59% (n = 478) underwent resection of their primary tumour, prior to trial entry (resection group). Compared to patients in the non-resection group (n = 332 [41%]), those in the resection group were more likely to have a colonic primary, lower baseline carcinoembryonic antigen (CEA) and alkaline phosphatase levels, and normal white-blood-cell count (p < 0.001 each). Primary tumour resection was independently associated to better OS in multivariate analysis (hazard ratio (HR), 0.63 [0.53–0.75]; p < 0.001, with a more favourable impact of resection on OS in case of rectal primary and low CEA level. Primary tumour resection was also independently associated to a better progression-free survival in multivariate analysis (HR, 0.82 [0.70–0.95]; p < 0.001).ConclusionPrimary tumour resection was independently associated to a better OS in patients with CRC and unresectable synchronous metastases.     

The impact of pelvic retroperitoneal invasion and distant nodal metastases in epithelial ovarian cancer

BackgroundThe absence of disease after debulking surgery is the most important prognostic factor in the treatment of advanced epithelial ovarian cancer (EOC). Occasionally, the presence of extra-abdominal disease complicates the ability to obtain a complete surgery, considering some locations of the metastatic disease as unresectable. The objective of the study was to estimate the survival impact of pelvic retroperitoneal invasion and extrapelvic and aortic distant nodal metastases in EOC patients. The anatomical landmarks of primary cytoreductive surgery will be discussed.Material and methodsWe reviewed data from 116 consecutive Mayo Clinic patients with epithelial ovarian cancer (EOC) stage IIIC and IV, undergoing primary cytoreduction surgery between 1996 and 2000. Univariate and multivariate analysis for patients with positive distant nodes and pelvic retroperitoneal invasion was performed, including 57 patients with no residual disease after surgery. Kaplan–Meier curves were used to estimate the probability of survival.ResultsThe median patient's age was 65 years (range 24–87 years). The 5 years overall survival was 44.8% (range 30.1–57.9 months) and the median length of survival was 39.9 months (range 0.13–60 months, 95% confidence interval: 30.1–57.9). Pelvic retroperitoneal invasion was present in 22 EOC patients (18.9%) and distant positive nodes were noted in 11 (9.5%): suprarenal/celiac (5.2%), inguinal (4.3%) and supraclavicular (0.9%). Univariate and multivariate Cox regression analysis, identified distant positive lymph nodes and pelvic retroperitoneal invasion as factors statistically associated with overall survival (p = 0.002 and p = 0.025, respectively).ConclusionsMetastatic distant nodes and pelvic retroperitoneal invasion are independent prognostic factors for survival in patients with advanced EOC.     

不能切除和复发的局部进展期胃癌放疗疗效分析

目的 回顾分析不能切除和复发的局部进展期胃癌行腹部放疗的疗效及影响因素。方法 回顾分析2009—2015年我院收治的57例患者,其中不能切除36例(包括局部晚期19例、术后肉眼残留17例),术后复发21例。接受3DCRT 17例、IMRT 40例,照射中位剂量50 Gy (42~60 Gy)。81%患者放疗同期口服氟尿嘧啶类药物化疗。结果 全组患者放疗后中位随访时间为16个月(3.9~77.5个月),放疗后缓解率65%。局部晚期、术后肉眼残留(R₂术后) 、术后复发组放疗后中位生存时间分别为13.9、13.9、19.0个月。全组放疗后2年的预期OS、PFS、LRRFS分别为50%、37%、50%。多因素分析显示病变分组是预后影响因素,而第3站淋巴结受侵并不是不良预后因素。结论 对不能切除及术后复发的局部进展期胃癌进行中等剂量放疗并结合化疗能取得较好的LC并改善患者生存,而术后复发和第3站淋巴结受侵病例均应被视为挽救性放化疗的良好适应征。     

Preoperative irradiation for tethered rectal carcinoma

Twenty-eight patients with resectable but tethered rectal carcinomas were treated with preoperative irradiation (EBRT) and surgical resection. The 5-year actuarial disease-free survival and local control rates of these 28 patients were 66 and 76%, respectively. Two patients have developed local failure only, 2 patients concurrent local failures and distant metastases, and 4 patients distant metastases only. All local failures occurred in areas of tumor adherence to unresectable structures (sacrum, pelvic side wall). Patients with tethered rectal tumors are at risk for local failure despite preoperative irradiation and surgical resection. To improve local control in this subset of patients, an intraoperative radiation therapy (IORT) boost is given to areas of tumor adherence at resection following EBRT.     

Preoperative radiation with concurrent 5-fluorouracil continuous infusion for locally advanced unresectable rectal cancer

Background and Purpose: To determine the percentage of complete responders and the resectability rate for patients with locally advanced carcinoma of the rectum treated by 5-fluorouracil (5-FU) infusional chemotherapy and pelvic radiation.Materials and Methods: Between October 1992 and June 1996, 29 patients with a diagnosis of locally advanced unresectable rectal cancer received preoperative 5 FU by continuous intravenous infusion at a dose of 225 mg/m²/day concurrent with pelvic radiation (median 54 Gy/28 fractions). All patients were clinical stage T4 on the bases of organ invasion or tumor fixation. Median time for surgical resection was 6 weeks.Results: Median follow-up for the group was 28 months (range 5–57 months). Six patients were felt to be persistently unresectable or developed distant metastases and did not undergo surgical resection. Of the 29 patients, 23 proceeded to surgery, 18 were resectable for cure, 13 by abdominoperineal resection, 3 by anterior resection and 2 by local excision. Of the 29 patients, 4 (13%) had a complete response, and 90% were clinically downstaged. Of the 18 resected patients, 1 has died of his disease, 17 are alive, and 15 disease-free. The regimen was well tolerated; there was only one treatment-related complication, a wound dehiscence.Conclusion: The combination of 5 FU infusion and pelvic radiation in the management of locally advanced rectal cancer is well tolerated and provides a baseline for comparison purposes with future combinations of newer systemic agents and radiation.     

术前同期放化疗治疗局部进展期中低位直肠癌疗效分析

目的 评价术前同期放化疗用于局部进展期中低位直肠癌的有效性和耐受性。方法 2007—2013年 共入组 51例 T₃、T₄期或N (+)的病理证实初治直肠癌患者。全盆腔三维放疗技术, 45.0~ 50.4 Gy分 25~ 28次;化疗采用FOLFOX4或XELOX方案,化疗在放疗开始第1、4周进行共2个周期;放化疗结束后 4~ 8周手术,术后1个月内开始行同方案巩固化疗。Kaplan-Meier 法计算生存率并 Logrank 检验和单因素分析及 Cox 模型行多因素预后分析。结果 49例 患者完成术前放化疗及手术治疗,中位随访时间2.9年 ,总保肛率为65%,总降期率为59%。pCR为20%。总≥3级不良反应发生率为25%,总并发症发生率为31%。3、5年 样本数分别为24、12例 ,3、5年 OS分别为81%、69%, DFS分别为76%、60%, LRFS分别为78%、70%,DMFS分别为82%、74%。多因素分析显示肿瘤降期为 5年 DFS、LRFS的独立预后因素。 结论 局部进展期中低位直肠癌术前放疗同期FOLFOX4或XELOX方案化疗能提高病理降期率和pCR率及保肛率,降期者可能有更好的生存优势。     

术前同步放化疗后yp0-Ⅰ期直肠癌预后分析

目的 探讨局部晚期直肠癌术前同步放化疗后yp0-Ⅰ期的预后及影响因素。方法 ２００８-２０１３ 年纳入研究８７ 例局部晚期直肠癌术前同步放化疗后ｙｐ０-Ⅰ期患者,均接受术前同步放化疗后４～８ 周进行ＴＭＥ。放疗给予全盆腔外照射４５.０～５０.４ Ｇｙ,同步给予单药卡培他滨或卡培他滨联合奥沙利铂化疗。采用Ｋａｐｌａｎ?Ｍｅｉｅｒ 法计算ＬＲＦＳ、ＤＭＦＳ、ＤＦＳ 和ＯＳ 并Ｌｏｇｒａｎｋ 检验和单因素预后分析,Ｃｏｘ 模型多因素预后分析。结果　术前同步放化疗与手术间隔中位时间为５１ ｄ。ＴＭＥ 术后共４５％接受了术后辅助化疗。３ 年ＬＲＦＳ、ＤＭＦＳ、ＤＦＳ 和ＯＳ 分别为９８％、９３％、９３％和９６％。多因素分析发现基于疗前临床分期和术后病理分期的降期深度评分与ＤＭＦＳ、ＤＦＳ 相关（Ｐ ＝ ０.０２０、０.００５）。降期深度评分５ 分为界值,预测３ 年ＤＦＳ 的ＲＯＣ 的ＡＵＣ 值为０.８０３。结论　术前同步放化疗后ｙｐ０-Ⅰ期直肠癌的长期生存结果较好。降期深度评分可以预测预后     

Adjuvant Treatment for Locally Advanced Rectal Cancer Patients After Preoperative Chemoradiotherapy: When,and for Whom?

BackgroundThe standard treatment for patients with locally advanced rectal cancer (clinical tumor, node, metastases [TNM] stage II or III) is radiotherapy before surgery (with or without concomitant fluoropyrimidine-based chemotherapy) followed by surgery. The role of adjuvant chemotherapy in this setting of patients is controversial in terms of the overall benefit on survival, the subgroup of patients who might not need it, and the best regimen (combination regimens vs. fluoropyrimidine alone).Patients and MethodsBased on the retrospective analysis of the clinical outcome of all patients with locally advanced rectal adenocarcinoma treated at our institute during the past 9 years, we comment on prognostic factors for local and distant metastases of patients who received neoadjuvant treatment followed by surgery, and the scientific evidence that can help to decide the adjuvant chemotherapy.ResultsWe conclude that pathological TNM stage after neoadjuvant chemoradiation (ypTNM) stage after surgery significantly affects disease-free and overall survival. In particular, patients with pathologically positive lymph nodes (ypN+) after surgery have a high probability of developing distant metastases.ConclusionypN+ patients are candidate for intensified adjuvant chemotherapy.     

Effective pelvic symptom control using initial chemoradiation without colostomy in metastatic rectal cancer

PURPOSE: To assess pelvic chemoradiotherapy (CXRT) without colostomy as a component of the multidisciplinary management of patients presenting with metastatic rectal cancer. METHODS AND MATERIALS: Eighty patients with synchronous distant metastases from rectal cancer were treated with initial CXRT. Hypofractionated radiotherapy was administered usually with concurrent 5-FU (92%, 300 mg/m(2)/day, M-F). Three-field belly-board technique was used in 89%. Group 1 had CXRT alone (n = 55). Group 2 (n = 25) patients were selected for primary disease resection, and sometimes HAI chemotherapy (n = 10) or hepatic resection (n = 5). Subsequently, 78% received systemic chemotherapy. RESULTS: Symptoms from primary tumor resolved in 94%. Endoscopic complete clinical response rate was 36%. Two-year survival (11% vs. 46%, p < 0.0001) and symptomatic pelvic control (PC, 81% vs. 91%, p = 0.111) were higher in Group 2, but colostomy-free rate (CFR) was lower (79% vs. 51% p = 0.02). CFR was 87% in Group 1 patients managed initially without fecal diversion (n = 50). Examining all patients using multivariate analysis, pelvic pain at presentation (p < 0.00001), BED (biologic equivalent dose at 2 Gy/fraction) < 35 Gy (p = 0.077), and poor differentiation (0.079) predicted worse PC. Poor differentiation (p = 0.017) and selection for CXRT alone (p < 0.0001) predicted worse survival. There were 4 RTOG of Grade 3 or greater acute complications, 5 severe perioperative complications, and no significant late treatment-related complications. CONCLUSION: Durable PC can be safely achieved without colostomy in most patients presenting with primary rectal cancer and synchronous systemic metastases using hypofractionated pelvic chemoradiation. A BED greater than 35 Gy is recommended. Selected patients appear to benefit from resection of primary disease. Higher doses should be investigated in patients with pelvic pain.     

47例局部晚期为主直肠癌放化疗临床分析

目的 探讨局部晚期为主直肠癌单纯放化疗疗效与预后因素分析。方法 回顾分析2003—2010年收治的47例放化疗为主的局部晚期直肠癌患者资料,其中3例单纯放疗。Kaplan-Meier法计算OS、PFS、DMFS并Logrank检验和单因素预后分析,Cox模型多因素预后分析。结果 全组3、5年OS率分别为53%和33%,PFS率分别为37%和31%。局部进展15例(32%),PFS期1~60个月(中位数14个月);远处转移23例(49%),DMFS期2~60个月(中位数17个月)。中剂量和高剂量放疗的3、5年局部进展率分别为54%和11%、57%和11%(P=0.004)。放化疗后pCR 9例(19%),其3、5年OS和PFS均8例。单因素分析显示肿瘤距肛门距离(P=0.026)和是否cCR (P=0.000)均是影响预后因素,但多因素分析仅cCR是影响生存的因素(HR=12.24,95%CI=1.64~91.29,P=0.015)。结论 因各种原因放弃手术治疗或未能行手术切除的局部晚期直肠癌,放化疗或单纯放疗是一种安全有效方法。高剂量放疗可提高直肠癌LC率,放化疗的获得CR预示良好的预后。     

Preoperative concomitant radiotherapy and chemotherapy in ultrasound-staged T3 and T4 rectal cancer

BACKGROUND: To analyze early results of a single institution's experience using neo-adjuvant chemoradiotherapy in locally advanced, ultrasound-staged rectal cancer. PATIENTS AND METHODS: Since 1998, 67 consecutive patients (36 males and 31 females; mean age, 59.5) have received preoperative combined treatment for T3 or T4 rectal cancer. All patients were staged by endorectal ultrasound and computed tomography, and all had a pathology-demonstrated invasive adenocarcinoma of the rectum. Patients were treated preoperatively with concomitant radiochemotherapy: pelvic irradiation (50 Gy in 25 fractions) and protracted-venous-infusion 5-fluorouracil (225 mg/m2/d, 7 days per week). Patients were restaged within 4 weeks, then submitted to surgery within 6-7 weeks after the end of therapy. Adjuvant postoperative chemotherapy with 5-fluorouracil plus folinic acid--the "de Gramont" schedule--for 24 weeks was purposed to all patients. RESULTS: Radiotherapy was completed in all cases; only one patient required suspension of the treatment for grade 4 toxicity (diarrhea). Instead, chemotherapy was interrupted in 3 cases (2 for central venous catheter thrombosis and 1 for grade IV diarrhea). Sixty-six patients underwent surgical resection (1 patient died before surgical treatment). Radical surgery was performed in 94%, and 46% of the 26 patients with distal rectal cancer had a conservative sphincter-sparing surgery. A complete pathologic response (defined as no evidence of viable tumor cells) was obtained in 22%. At a median follow-up of 17 months, distant metastases have been observed in 10 patients, and 3 of them developed a local recurrence. The actuarial estimations of 4-year overall survival, disease-free survival, local and distant control are 79%, 61%, 94% and 61%, respectively. CONCLUSIONS: Preoperative chemoradiotherapy seems to be an effective and well-tolerated treatment with a low complication rate. The high percentage of down-staging and sphincter sparing, also in distal rectal cancer, shows the efficacy of the treatment, which could significantly influence the incidence of relapses and quality of life.     

Prognostic Significance of Weight Gain During Definitive Chemoradiotherapy for Locally Advanced Non–Small-Cell Lung Cancer

BackgroundThe successful treatment of locally advanced non–small-cell lung cancer (NSCLC) with chemoradiotherapy (CRT) is still compromised by poor locoregional and distant control rates. Given the morbidity associated with treatment, it is critical to determine clinical prognostic factors to risk stratify patients before and after aggressive therapy. This study aimed to discern the prognostic value of weight gain during CRT in patients with locally advanced NSCLC.Patients and MethodsThis was a retrospective analysis of 92 patients treated with definitive split-course CRT between 2004 and 2010 at Rush University Medical Center. Weight gain was defined as a weight change greater than the highest quartile of change between the start and finish of CRT (4.5 lb). Overall survival (OS), locoregional progression-free survival (PFS), and distant metastasis-free survival (DMFS) were determined using Kaplan-Meier analysis, and the cumulative incidences of locoregional and distant recurrence were calculated. Cox regression (multivariate analysis) was used to determine independent predictors of OS.ResultsWith a median follow-up of 50 months for surviving patients, the median, 3- and 5-year OS probabilities were 25 months, 37%, and 29%, respectively. The 3-year cumulative risks of locoregional and distant metastases were 51% and 64%. Patients who experienced weight gain were significantly more likely to survive (3-year OS, 55% vs. 31%; P = .04) and prolonged DMFS resulted. Weight gain was the only significant predictor of survival on multivariate analysis.ConclusionsWeight gain during split-course CRT was associated with superior OS and DMFS. The presence of weight gain may have utility in risk stratification after CRT as well as in identifying novel treatment approaches for patients with locally advanced NSCLC.     

Preoperative chemoradiation and IOERT for unresectable or borderline resectable pancreas cancer

Background and objectives

Pre-operative chemoradiation (preop CRT) plus intraoperative electron irradiation (IOERT) has been used in the multidisciplinary treatment for patients with locally advanced unresectable or borderline resectable pancreas cancer. This review was performed to evaluate survival, relapse patterns and prognostic factors in patients treated with curative intent.

Methods

Between January 2002 and December 2010, 48 patients with locally advanced pancreatic ductal adenocarcinoma received preop CRT prior to an attempt at resection and IOERT. 31/48 (65%) patients proceeded to curative-intent surgical resection. Resection status prior to preop CRT was locally unresectable (20 patients) and borderline resectable (11 patients). Preop CRT (45-50.4 Gy/25-28 Fx in 27/31) was delivered with concurrent 5FU or gemcitabine-based regimens. Subsequent gross total resection was achieved in 16 patients (R0, 11; R1, 5). IOERT was delivered in 28 patients (dose, 10-20 Gy). 16 patients also received adjuvant post-operative systemic chemotherapy. Outcomes evaluated include survival, local failure in the EBRT field (LF), central failure in the IOERT field (CF), and distant metastases.

Results

Resection status was predictive for survival and for patterns of relapse. For patients with at least a gross total resection after preop CRT (R0/R1; n=16) vs. no resection (n=15), both median and overall survival were improved (median 23 vs. 10 months; 2-year, 40% vs. 17%; 3-year, 40% vs. 0%; P=0.002). Liver or peritoneal relapse was documented in 22/31 patients (71%); LF/CF in 5/26 (16%).

Conclusions

Long term survival and disease control are achievable in select patients with borderline resectable or locally unresectable pancreas cancer when gross total surgical resection is achieved after preop CRT. Continued evaluation of curative-intent combined modality therapy is warranted in this high risk population, but additional strategies are needed to improve resectability and disease control.Key Words: Pancreatic neoplasms, radiotherapy, chemotherapy, surgery, intraoperative procedures     

Liposome-paclitaxel and carboplatin combination chemoradiotherapy for patients with locally advanced esophageal squamous cell carcinoma

PurposeThe aim of this study was to evaluate the efficacy of liposome-paclitaxel and carboplatin combination chemoradiotherapy for patients with locally advanced esophageal squamous cell carcinoma (ESCC).Patients and methodsSeventy-nine consecutive patients treated with liposome-paclitaxel based concurrent chemoradiotherapy between January 2015 and December 2019 at Cancer hospital of the University of Chinese Academy of Sciences (Zhejiang cancer hospital) were enrolled in this study. The overall response, toxicities, progression-free survival and overall survival were analyzed with SPSS software.ResultsA total of 302 cycles of weekly chemotherapy were delivered, with a median 4 courses. After concurrent chemoradiotherapy (CCRT), the efficacy was classified as CR in 4 cases (5.1%), PR in 22 cases (28.2%) and SD in 51 cases (65.4%). The median PFS and OS time were 18.2 months and 23.4 months. The 3-year PFS and OS rates were 45.1% and 43.6%, respectively.ConclusionsLiposome-paclitaxel and carboplatin concurrent with radiotherapy is a safe and effective modality for locally advanced ESCC. Further clinical investigation are warranted to evaluate the efficacy of this regimen.