Patterns of locoregional failure in stage III non-small cell lung cancer treated with definitive chemoradiation therapy

PurposeChemoradiation therapy (CRT) is the core treatment of locally advanced non-small cell lung cancer (LA-NSCLC), but potential toxicities limit radiation therapy dose. These toxicities, plus the advent of increasingly conformal radiation therapy, have prioritized target definition and the use of involved-field radiation therapy (IFRT). Published data largely focus on regional rather than local failure patterns. We report our pattern-of-failure experience treating patients with LA-NSCLC with definitive CRT, focusing on both local and regional recurrences with detailed dosimetric analyses of failure location.Methods and materialsPatients treated between December 2004-2010 were included. Imaging scans from date of failure were fused with the RT-planning CT scan, and recurrent nodes were contoured to determine if the recurrence was in a previously irradiated region, defined as involved nodal recurrence (INR) versus elective nodal recurrence (ENR). Local failures were contoured and identified as in-field, marginal, or out-of-field based on dose received. Actuarial overall survival (OS) and progression-free survival (PFS) were calculated, and the cumulative incidences of local, regional, locoregional, and distant recurrence (CILR, CIRR, CILRR, CIDR) were determined with death as a competing risk.ResultsOne hundred five patients were included with a median survival of 21.8 months. The 3-year OS and PFS were 36% and 22%, respectively. The 3 year CILRR, CILR, CIRR, CIDR were 41%, 38%, 40%, and 58%, respectively. Thirty patients failed regionally, but only 7 patients developed an ENR with no concurrent local failure or INR, and only 1 of these patients did not develop distant metastases within 1 month of recurrence. A total of 21 patients (20%) developed an ENR with or without other areas of recurrence.ConclusionsElective regional recurrences rarely occurred as the sole site of failure, despite the use of IFRT. Moreover, the pattern of local failure was entirely in-field. These data strongly support field design focusing on gross nodal and primary disease.     

累及野调强放疗联合同步化疗治疗局部晚期非小细胞肺癌的疗效观察

目的比较累及野照射（IFI）和选择性淋巴结照射（ENI）调强放射治疗联合同步化疗治疗局部晚期非小细胞肺癌（LA-NSCLC）的不良反应和疗效。方法49例LA-NSCLC患者前瞻性随机分为IFI组和ENI组,同步化疗两周期,行根治性调强放射治疗。结果IFI组和ENI组≥2级放射性肺炎发生率分别为8.0％和37.5％（P=0.01）;GTV平均剂量分别是（66.2±6.5）Gy和（61.3±6.3）Gy,（P=0.01）;总有效率为92.0％和66.7％（P=0.03）;预防照射区内淋巴结复发率为4.2％和4.0％,（P=0.49）;1年局部失败率分别为8.0％和16.7％（P=0.62）;1年生存率为72.0％和62.5％（P=0.48）。结论IFI同步放化疗治疗LA-NSCLC可降低正常组织并发症的概率,提高靶区照射剂量和肿瘤控制率,预防照射区内淋巴结复发率无增加,有望延长患者生存期。     

局部晚期非小细胞肺癌累及野和选择性淋巴结照射前瞻性随机研究

目的 前瞻性比较局部晚期非小细胞肺癌(LA-NSCLC)采用累及野照射(IFRT)或选择性淋巴结照射(ENI)局部失败的差异及对生存的影响。方法 99例LA-NSCLC经紫杉醇加卡铂化疗2周期后无远处转移患者随机分为IFRT组(45例)或ENI组(54例),IFRT组照射原发病灶、同侧肺门和纵隔阳性淋巴结,ENI组照射原发病灶、同侧肺门、双侧中上纵隔淋巴引流区及双侧锁骨上区。在满足双肺 V₂₀≤35%、脊髓受量≤50 Gy条件下给予尽可能高剂量,每周紫杉醇40 mg/m²放疗增敏。采用Kaplan-Meier法计算生存率并Logrank法检验。结果 随访率为99%,随访时间满1、2、3年者分别为49、29、17例。IFRT组与ENI组放疗剂量>60 Gy的分别占49%和26%(χ²=5.59,P=0.018),局部失败率分别为29%和36%(χ²=0.46,P=0.497),1、2、3年局部无进展生存率分别为76%、69%、65%和80%、53%、49%(χ²=0.74,P=0.389),1、3、5年总生存率分别为80%、41%、33%和69%、32%、13%(χ²=3.97,P=0.046)。两组不良反应相似(χ²=3.91~0.16,P=0.142~0.925)。结论 IFRT较ENI照射剂量高并增加了总生存率,未增加选择性照射区淋巴结复发率,不良反应相近,还需大样本研究。     

Combined chemoradiation vs radiation therapy alone in stage-II nasopharyngeal carcinoma: A meta-analysis of the published literature

The aim of this meta-analysis was to evaluate the efficacy and toxicity of adding chemotherapy to radiotherapy (RT) in the treatment of stage-II nasopharyngeal carcinoma (NPC). We searched Pubmed, Cochrane Library, Embase, China National Knowledge Internet, China Biology Medicine, VIP, and Wanfang database for studies of the RT with or without chemotherapy in patients with stage-II NPC that were published in any language. Analyses were carried out using RevMan 5.3 software. The relative risk was used to evaluate the data, the I² test was used to compare heterogeneity, sensitivity analysis was used to evaluate the stability and reliability of the results. There were 16 studies with 3038 patients that were included in this analysis. Risk ratios (RR) of 1.04 (95% CI: 1.01-1.06), 1.05 (95% CI: 1.00-1.10), 1.05 (95% CI: 1.02-1.07), and 1.00 (95% CI: 0.97-1.03) were observed for overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFS), and distant metastasis-free survival (DMFS). Subgroup analysis showed that compared with conventional RT alone, chemoradiation (CRT) could significantly improve OS (RR = 1.09, 95% CI: 1.03-1.15), PFS (RR = 1.20, 95% CI: 1.08-1.35), and LRFS (RR = 1.09, 95% CI: 1.04-1.14), but did not significantly improve the rate of DMFS (RR = 1.03, 95% CI: 0.94-1.12). However, compared with intensity modulated radiation therapy alone, CRT did not significantly improve the rate of OS (RR = 1.01, 95% CI: 0.99-1.03), PFS (RR = 0.99, 95% CI: 0.95-1.03), LRFS (RR = 1.02, 95% CI: 0.99-1.05), and DMFS (RR = 0.99, 95% CI: 0.96-1.01). Compared with conventional RT alone, CRT could significantly improve patients’ prognoses in terms of OS, PFS, and LRFS for stage-II NPC, but not DMFS, and CRT can provide greater benefits from concurrent chemotherapy than neoadjuvant chemotherapy. With intensity modulated radiation therapy, the stage-II NPC patients did not benefit from the addition of chemotherapy.     

Involved-field irradiation concurrently combined with nedaplatin/5-fluorouracil for inoperable esophageal cancer on basis of 18FDG-PET scans: A phase II study

PurposeA prospective study was performed on chemoradiotherapy (CRT) for esophageal cancer using involved-field radiation therapy (IFRT) based on 18-fluorodeoxyglucose positron-emission tomography. The goal of this phase II study was to evaluate the efficacy of the IFRT procedure in newly diagnosed esophageal cancer.Patients and methodsEligible patients were adults with newly diagnosed untreated, inoperable esophageal cancer in stages I–IV with lymph node metastases. Patients received nedaplatin 80 mg/m² per day on day 1, 5-fluorouracil 800 mg/m² on days 1–4 intravenously repeated every 28 days for 2–4 cycles, and combined IFRT. Elective nodal irradiation was not performed. Irradiation was applied only to the primary tumor and positive lymph nodes.ResultsFrom September 2009 to July 2012, of the 63 patients enrolled, 58 were evaluable for response. The primary end point of isolated out-of-field loco-regional nodal recurrence was seen in only two patients. The expectant rate was assumed to be less than 5%. The threshold value was set as 10% to calculate the number of registrations. Progression-free and overall survival rates at 36 months were 47.7% and 51.1%, respectively. The median progression-free survival was 34.6 months, and overall survival was 38.4 months. Salvage surgery was tried for 11 patients (17.5%) due to residual or recurrent disease.ConclusionThe primary end point of the trial was demonstrated, indicating the efficacy of IFRT in the treatment of inoperable esophageal cancer mostly of squamous cell carcinoma.     

Prognostic factors of dose-response relationship for nodal control in metastatic lymph nodes of cervical cancer patients undergoing definitive radiotherapy with concurrent chemotherapy

ObjectiveRegional control is occasionally unsatisfactory in cervical cancer, with the optimal radiation dose for nodal metastases in definitive radiotherapy (RT) with concurrent chemotherapy (CRT) remaining controversial. We investigated dose-response relationship for nodal local control in cervical cancer.MethodsWe identified 115 patients with 417 metastatic nodes who received definitive CRT for cervical cancer with nodal metastases. External beam radiation therapy and brachytherapy plans were summated to determine total dose received by each node. Prognostic factors of nodal control and dose-response relationship were investigated using Cox-regression and restricted cubic spline function.ResultsThe 2-year progression-free survival rate was 69.4%. Among 43 patients with failures, 17 patients (37.5%) had regional failure included in first failure sites of which all except one were in-field only regional failures. Total 30 nodes showed recurrence at initial metastatic site after treatment. Neutrophil-to-lymphocyte ratio (NLR) ≥3.1, total radiation dose (minimum dose received by 98% of the target volume in equivalent dose in 2 Gy per fractions), and initial nodal volume ≥5.29 mL were poor prognostic factors (all p<0.050) of nodal local control. Restricted cubic spline functions revealed strongest dose-response relationship in high NLR (NLR ≥3.1) and initial nodal volume ≥5.29 mL subgroup.ConclusionInitial nodal volume, radiation dose_, and NLR were significant factors of nodal local control in cervical cancer; a stronger dose-response relationship was seen in bulky nodes with high NLR. Clinicians may consider these factors when determining the RT dose and the need for boost to nodal metastases in cervical cancer.     

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.     

Phase II Study: The Outcome of Hypofractionated Involved-Field Radiation Therapy With Concurrent Chemotherapy for the Treatment of Locally Advanced Non-small Cell Lung Cancer

PurposeThis phase II study aimed to evaluate the efficacy and safety of hypofractionated involved-field radiation therapy (HypoFx-IFRT) in 2.5 Gy fractions and concurrent chemotherapy for locally advanced stage IIIA and B nonsmall cell lung cancer (LA-NSCLC) without prolonging treatment delivery time beyond 6 weeks. We analyzed the overall survival (OS), progression-free survival, and safety of the treatment.Methods and MaterialsThis prospective, single center, single-arm trial was initiated in 2010. All LA-NSCLC patients were treated with HypoFx-IFRT using 3-dimensional conformal radiation therapy. The median total dose of HypoFx-IFRT was 67.5 Gy (range, 60-70).ResultsFrom December 2010 to October 2016, 36 patients were ultimately enrolled and evaluated. The trial closed early owing to slow accrual. The median follow-up duration was 50 months in all patients and 65 months in surviving patients. The 1-, 3-, and 5-year OS rates were 88.9% (95% confidence interval [CI], 78.6%-99.2%), 61.1% (95% CI, 45.2%-77.0%), and 54.1% (95% CI, 37.3%-70.9%), respectively. The median time for OS was not reached. The median time for progression-free survival was 10.7 months. The incidence rates of grade 3 radiation pneumonitis, esophagitis and esophageal stenosis were 8.3%, 2.8%, and 2.8%, respectively, and no acute or late toxicities of grade 4 or 5 were observed.ConclusionsThis study indicated that HypoFx-IFRT with concurrent chemotherapy yielded an acceptable safety profile and might be beneficial in the survival outcomes of patients with LA-NSCLC.     

Elective nodal irradiation (ENI) vs. involved field radiotherapy (IFRT) for locally advanced non-small cell lung cancer (NSCLC): A comparative analysis of toxicities and clinical outcomes

Background

Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with locally advanced non-small cell lung cancer (NSCLC). ENI delivers prophylactic radiation to clinically uninvolved lymph nodes, while IFRT only targets identifiable gross nodal disease. Because clinically uninvolved nodal stations may harbor microscopic disease, IFRT raises concerns for increased nodal failures. This retrospective cohort analysis evaluates failure rates and treatment-related toxicities in patients treated at a single institution with ENI and IFRT.

Methods

We assessed all patients with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy from 2003 to 2008. Each physician consistently treated with either ENI or IFRT, based on their treatment philosophy.

Results

Of the 108 consecutive patients assessed (60 ENI vs. 48 IFRT), 10 patients had stage IV disease and 95 patients received chemotherapy. The median follow-up time for survivors was 18.9 months. On multivariable logistic regression analysis, patients treated with IFRT demonstrated a significantly lower risk of high grade esophagitis (Odds ratio: 0.31, p = 0.036). The differences in 2-year local control (39.2% vs. 59.6%), elective nodal control (84.3% vs. 84.3%), distant control (47.7% vs. 52.7%) and overall survival (40.1% vs. 43.7%) rates were not statistically significant between ENI vs. IFRT.

Conclusions

Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients.     

Locally Advanced Non-Small Cell Lung Cancer: Clinical Outcome,Toxicity and Predictive Factors in Patients Treated with Hypofractionated Sequential or Exclusive Radiotherapy

Background: This study evaluated the outcome, toxicity and predictive factors in patients unfit for concurrent chemo-radiotherapy (CT-RT) treated with hypofractionated sequential CT-RT or exclusive radiotherapy (RT) for locally advanced non-small cell lung cancer (LA-NSCLC). Methods: We included patients affected by LA-NSCLC (stage IIA-IVA) treated with a total dose of 50–60 Gy in 20 fractions. The primary outcomes were local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS). Univariate analysis was used to correlate outcomes with prognostic factors. Results: Between 2011 and 2019, 210 patients were treated, 113 (53.8%) with sequential CT-RT and 97 (46.2%) with exclusive RT. After a median follow-up of 15.3 months, 74 patients (35.2%) had a local progression and 133 (63.3%) had a distant progression. The one-, two- and five-year LC were 73.6%, 55.3% and 47.9%, respectively. At the time of analysis, 167 patients (79.5%) died. The one-, two- and five-year OS were 64.7%, 36% and 20%, respectively. PTV volume correlated with PFS (p = 0.001) and LC (p = 0.005). Acute and late toxicity occurred in 82% and 26% of patients. Conclusions: Albeit with the known limitations of a retrospective and heterogeneous study, our work shows that hypofractionated sequential CT-RT or exclusive RT offer a good local control and toxicity profile and a promising survival rate in LA-NSCLC patients unfit for the concurrent CT-RT scheme.     

Sphincter-sparing local excision and adjuvant radiation for anal-rectal melanoma.

PURPOSE: To evaluate the outcome and toxicity of a sphincter-sparing treatment strategy in the management of patients with anal-rectal melanoma. PATIENTS AND METHODS: Between 1989 and 2000, 23 patients with invasive anal-rectal melanoma were managed with sphincter-sparing surgical resection and adjuvant radiation. Surgery consisted of primary local excision, as well as dissection for patients with documented regional nodal disease. Adjuvant radiation was delivered using a hypofractionated regimen of 30 Gy in five fractions over 2.5 weeks. Adjuvant systemic therapy was delivered to nine patients: cytotoxic chemotherapy in seven and immunotherapy in two. RESULTS: After a median follow-up of 32 months, 15 patients had relapsed and 15 patients had died. The actuarial 5-year overall, disease-specific, disease-free, and distant metastasis-free survival rates were 31%, 36%, 37%, and 35%, respectively. The actuarial 5-year local and regional nodal control rates were 74% and 84%, respectively. No patient had locoregional failure as the sole site of failure and no patient required salvage abdominoperineal resection (APR). By univariate analysis, patients with nodal disease at presentation had a decreased actuarial 5-year disease-specific (0% v 45%, P =.004), disease-free (0% v 45%, P <.001), and distant metastasis-free survival (0% v 42%, P <.001). The actuarial complication-free survival rate was 71%. Two patients developed mild scrotal edema (grade 1), and four patients developed moderate proctitis requiring prolonged medical management (grade 2). CONCLUSION: Sphincter-sparing local excision and adjuvant radiation is well tolerated and can effectively control local-regional disease while avoiding the functional morbidity of APR.     

临床T1~2N0~1M0食管癌放疗长期疗效、治疗失败原因和选择性淋巴结照射结果分析

目的 明确和评价临床可手术切除食管癌放射治疗的疗效,分析其治疗失败的原因,同时对选择性淋巴结照射的可行性进行分析。方法　对可能影响入组食管癌患者预后的生存因素进行分析,并对其死亡原因进行详细分析。同时对进行了选择性淋巴结照射的21例患者的生存相关情况与其他102例患者进行了比较研究。疾病治疗失败原因分为复发、远处转移和淋巴结转移。结果 全组患者1、3、5年总生存率及局部控制率分别为87.8%、47.2%、36.5%和89.7%、67.7%、49.0%。多因素分析显示病变X线长度、临床N分期及近期疗效是其独立的预后因素。选择性淋巴结照射并未给患者生存及局控率上带来益处,但对纵膈淋巴结转移和（或）远处转移患者有益（χ2=5.778,P=0.016）。结论 三维适形放射治疗可作为早期食管癌有效的治疗方式之一;选择性淋巴结照射可能会降低淋巴结转移率,但需要后续进一步研究证实,是否能提高患者的生存率也有待进一步研究。     

Pathologic Implications of Magnetic Resonance Imaging-detected Extramural Venous Invasion of Rectal Cancer

BackgroundExtramural venous invasion (EMVI) is a poor prognostic factor in rectal cancer. Recent advances in magnetic resonance imaging (MRI) allow for the detection of EMVI before surgery. This study aimed to analyze the correlations between MRI-detected EMVI (MR-EMVI) and pathologic parameters in patients with rectal cancer.Materials and MethodsThis study retrospectively analyzed 721 patients who underwent radical resection for locally advanced rectal cancer between 2018 and 2019 at the Asan Medical center. All patients underwent an MRI before surgery. The lesions of patients who received neoadjuvant chemoradiation therapy (CRT) were evaluated by MRI before and after the neoadjuvant CRT.ResultsOf the 721 patients, 118 (16.4%) showed a positive MR-EMVI, which significantly correlated with advanced pathologic T-category and N-category, extranodal extension, poor differentiation, lymphatic invasion, venous invasion, and perineural invasion. In addition, MR-EMVI was an independent factor for predicting the pathologic nodal status (OR 3.476, 95% CI, 2.186-5.527, P < .001). Patients with a positive MR-EMVI had a sensitivity of 28.0% and specificity of 91.9% for predicting regional lymph node metastasis, whereas the MR-N category had a sensitivity of 88.7% and specificity of 30.6%. Patients whose MR-EMVI changed from positive to negative after neoadjuvant CRT had no significant differences in pathologic parameters except for lymphatic invasion with patients who were negative before and after neoadjuvant CRT.ConclusionMR-EMVI correlated with aggressive pathologic features, which indicated a poor prognosis. MR-EMVI may be a complementary imaging biomarker for predicting nodal status and evaluating tumor response to neoadjuvant CRT.     

乳腺癌全乳房切除术后单纯区域复发的放疗和预后分析

目的 分析乳腺癌全乳房切除术后单纯区域复发(RR)患者的预后,探讨放疗的价值和靶区。方法 回顾性分析2001-2018年间 144例全乳房切除术后无辅助放疗、首次孤立性RR的乳腺癌患者,主要研究终点为再次局部区域复发(sLRR)、远处转移(DM)、无进展生存(PFS)和总生存(OS)。结果 RR后中位随访82.5个月,全组患者 5年sLRR、DM、PFS和OS分别为42.1%、71.9%、22.9%和62.6%。局部治疗+全身治疗是sLRR (P<0.001)和PFS (P=0.013)的独立影响因素。局部治疗时手术+放疗组的sLRR率最低(P<0.001)。手术+放疗组的 5年原RR部位再次复发率最低(P<0.001)。做和不做胸壁放疗患者的 5年胸壁复发率分别为12.1%和14.8%(P=0.873)。非锁骨上复发者,做和不做锁骨上放疗的 5年锁骨上复发率分别为9.9%和23.8%(P=0.206)。非腋窝或内乳复发者,无论放疗与否,腋窝或内乳的 5年复发率均<10%。结论 单纯RR患者有较高的 5年OS,推荐对复发部位行手术+放疗的局部治疗联合全身治疗。不建议常规对所有患者行胸壁、腋窝或内乳的预防放疗。锁骨上预防性放疗的价值需要进一步探讨。     

Results of a preliminary study using hypofractionated involved-field radiation therapy and concurrent carboplatin/paclitaxel in the treatment of locally advanced non-small-cell lung cancer

Background

We aimed to evaluate the feasibility and efficacy of hypofractionated involved-field radiation therapy (IFRT) omitting elective nodal irradiation (ENI) with concurrent chemotherapy for locally advanced non-small-cell lung cancer (NSCLC).

Methods

Between July 2004 and July 2006, ten patients with locally advanced NSCLC were included in this study. One had stage IIIA and 9 had stage IIIB disease. The treatment consisted of IFRT in fractions of 2.5 Gy and weekly carboplatin (CBDCA)/paclitaxel (PTX). Hypofractionated IFRT with a median total dose of 65 Gy with median percent total lung volume exceeding 20 Gy (V20) of 20.2%, and a median of five courses of chemotherapy with weekly CBDCA (area under the curve, 1.5?2.0)/PTX (30?35 mg/m²) were given to all patients.

Results

The median survival time and the 1-, 2-, and 3-year overall survival rates were 29.5 months and 90.0%, 58.3%, and 43.8%, respectively. No elective nodal failure was encountered during the median follow up of 18.2 months. No acute or late toxicities of grade 3 or worse were observed. No in-field recurrence occurred in the group with a total dose of 67.5 Gy or more, but there was such recurrence in 83.3% of those in the group with less than 67.5 Gy.

Conclusion

Hypofractionated IFRT with weekly CBDCA/PTX was a feasible treatment regimen. Hypofractionated IFRT with a total dose of 67.5 Gy or more could be a promising modality to improve the treatment results in patients with locally advanced NSCLC.     

Pretreatment prognostic factors in patients with early-stage (I/II) non-small-cell lung cancer treated with hyperfractionated radiation therapy alone

PURPOSE: To investigate influence of various pretreatment prognostic factors in patients with early stage (I/II) non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy alone. PATIENTS AND METHODS: One hundred and sixteen patients were treated with tumor doses of 69.6 Gy, 1.2-Gy, twice-daily fractionation. There were 49 patients with Stage I and 67 patients with Stage II. Eighty patients had Karnofsky performance status (KPS) 90-100 and 95 patients had <5% weight loss. Peripheral tumors were observed in 57 patients. Squamous histology was observed in 70 patients and the majority of patients had concomitant disease (n=72). RESULTS: The median survival time for all patients was 29 months; 5-year survival was 29%. The median time to local progression and the distant metastasis were not achieved, whereas 5-year local progression-free and distant metastasis-free survivals were 50% and 72%, respectively. Multivariate analysis identified KPS, weight loss, location, histology, and the reason for not undergoing surgery as prognostic factors for survival. KPS, location, and histology influenced local progression-free survival, whereas only KPS and weight loss influenced distant metastasis-free survival. CONCLUSIONS: This retrospective analysis identified KPS and weight loss as the most important prognostic factors of outcome in patients with early-stage NSCLC treated with hyperfractionation radiation therapy.     

Ablative 5-Fraction Stereotactic Magnetic Resonance–Guided Radiation Therapy With On-Table Adaptive Replanning and Elective Nodal Irradiation for Inoperable Pancreas Cancer

PurposeRadiation therapy dose escalation using stereotactic body radiation therapy may significantly improve both local control (LC) and overall survival (OS) for patients with inoperable pancreas cancer. However, ablative dose cannot be routinely offered because of the risk of causing severe injury to adjacent normal organs. Stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) represents a novel technique that may achieve safe delivery of ablative dose and improve long-term outcomes.Methods and MaterialsWe performed a single institution retrospective analysis of 35 consecutive pancreatic cancer patients treated with SMART in mid-inspiration breath hold on an MR-linear accelerator. Most had locally advanced disease (80%) and received induction chemotherapy (91.4%) for a median 3.9 months before stereotactic body radiation therapy. All were prescribed 5 fractions delivered in consecutive days to a median total dose of 50 Gy (BED₁₀ 100 Gy₁₀), typically with a 120% to 130% hotspot. Elective nodal irradiation was delivered to 20 (57.1%) patients. No patient had fiducial markers placed and all were treated with continuous intrafraction MR visualization and automatic beam triggering.ResultsWith median follow-up of 10.3 months from SMART, acute (2.9%) and late (2.9%) grade 3 toxicities were uncommon. One-year LC, distant metastasis-free survival, progression-free survival, cause-specific survival, and OS were 87.8%, 63.1%, 52.4%, 77.6%, and 58.9%, respectively.ConclusionsTo our knowledge, this is the first report of 5-fraction pancreas SMART delivered on an MR-linear accelerator. We observed minimal severe treatment-related toxicity and encouraging early LC. Prospective confirmation of feasibility and long-term clinical outcomes of dose intensified SMART is warranted.     

Survival After Induction Chemotherapy and Chemoradiation Versus Chemoradiation and Adjuvant Chemotherapy for Locally Advanced Rectal Cancer

BackgroundTotal neoadjuvant therapy (TNT) improves tumor response in locally advanced rectal cancer (LARC) patients compared to neoadjuvant chemoradiotherapy alone. The effect of TNT on patient survival has not been fully investigated.Materials and MethodsThis was a retrospective case series of patients with LARC at a comprehensive cancer center. Three hundred and eleven patients received chemoradiotherapy (chemoRT) as the sole neoadjuvant treatment and planned adjuvant chemotherapy, and 313 received TNT (induction fluorouracil and oxaliplatin-based chemotherapy followed by chemoradiotherapy in the neoadjuvant setting). These patients then underwent total mesorectal excision or were entered in a watch-and-wait protocol. The proportion of patients with complete response (CR) after neoadjuvant therapy (defined as pathological CR or clinical CR sustained for 2 years) was compared by the χ² test. Disease-free survival (DFS), local recurrence-free survival, distant metastasis-free survival, and overall survival were assessed by Kaplan-Meier analysis and log-rank test. Cox regression models were used to further evaluate DFS.ResultsThe rate of CR was 20% for chemoRT and 27% for TNT (P=.05). DFS, local recurrence-free survival, metastasis-free survival, and overall survival were no different. Disease-free survival was not associated with the type of neoadjuvant treatment (hazard ratio [HR] 1.3; 95% confidence interval [CI] 0.93-1.80; P = .12).ConclusionsAlthough TNT does not prolong survival than neoadjuvant chemoradiotherapy plus intended postoperative chemotherapy, the higher response rate associated with TNT may create opportunities to preserve the rectum in more patients with LARC.     

Phase II Study of Immunotherapy With Tecemotide and Bevacizumab After Chemoradiation in Patients With Unresectable Stage III Non-Squamous Non–Small-Cell Lung Cancer (NS-NSCLC): A Trial of the ECOG-ACRIN Cancer Research Group (E6508)

IntroductionAlthough chemoradiotherapy (CRT) is the standard of care for patients with unresectable stage III non–small-cell lung cancer (LA-NSCLC), most patients relapse. Tecemotide is a MUC1 antigen-specific cancer immunotherapy vaccine. Bevacizumab improves survival in advanced nonsquamous (NS)-NSCLC and has a role in immune modulation. This phase II trial tested the combination of tecemotide and bevacizumab following CRT in patients with LA-NSCLC.Patients and MethodsSubjects with stage III NS-NSCLC suitable for CRT received carboplatin/paclitaxel weekly + 66 Gy followed by 2 cycles of consolidation carboplatin/paclitaxel ≤ 4 weeks of completion of CRT (Step 1). Patients with partial response/stable disease after consolidation therapy were registered onto step 2, which was 6 weekly tecemotide injections followed by every 6 weekly injections and bevacizumab every 3 weeks for up to 34 doses. The primary endpoint was to determine the safety of this regimen.ResultsSeventy patients were enrolled; 68 patients (median age, 63 years; 56% male; 57% stage IIIA) initiated therapy, but only 39 patients completed CRT and consolidation therapy per protocol, primarily owing to disease progression or toxicity. Thirty-three patients (median age, 61 years; 58% male; 61% stage IIIA) were registered to step 2 (tecemotide + bevacizumab). The median number of step 2 cycles received was 11 (range, 2-25). Step 2 worst toxicity included grade 3, N = 9; grade 4, N = 1; and grade 5, N = 1. Grade 5 toxicity in step 2 was esophageal perforation attributed to bevacizumab. Among the treated and eligible patients (n = 32) who were treated on step 2, the median overall survival was 42.7 months (95% confidence interval, 21.7-63.3 months), and the median progression-free survival was 14.9 months (95% confidence interval, 11.0-20.9 months) from step 1 registration.ConclusionsThis cooperative group trial met its endpoint, demonstrating tolerability of bevacizumab + tecemotide after CRT and consolidation. In this selected group of patients, the median progression-free survival and overall survival are encouraging. Given that consolidation immunotherapy is now a standard of care following CRT in patients with LA-NSCLC, these results support a role for continued investigation of antiangiogenic and immunotherapy combinations in LA-NSCLC.     

Effect of Positive Surgical Margins in Patients Who Undergo a Partial Nephrectomy Regarding Recurrence,Overall Survival,Recurrence/Progression-Free Survival,and Metastasis-Free Survival. A Systematic Review and Meta-Analysis

BackgroundTo determine the effect of positive surgical margins in patients who undergo a partial nephrectomy regarding recurrence, overall survival, disease-free survival, recurrence and progression-free survival, and metastasis-free survival.MethodsWe performed a systematic review accomplishing with Cochrane recommendations. We searched in Medline, Embase, and central. We also looked for unpublished literature. There was no language or setting restrictions. We performed a random-effects meta-analysis for all outcomes.ResultsWe included 44 studies for qualitative and quantitative analysis. We found that positive margins increase the risk of local recurrence (RR 4.14 95%CI 2.75-6.24), recurrence (RR 4.8 95%CI 3.38-6.62), mortality (RR 1.83 95%CI 1.08-3.1), metastasis (RR 8.1 95%CI 3.88-16.92), and improved the recurrence/progression-free survival (HR 2.9 95%CI 1.88-4.49) and metastasis-free survival (HR 2.91 95%CI 1.25-6.79) with moderate, moderate, very low, very low, and high certainty of the evidence, respectively. We found no change in overall survival (HR 1.48 95%CI 0.98-2.22) with very low certainty of evidence.ConclusionsA positive margin is an independent predictor of local recurrence, recurrence, mortality, metastasis, with no effect on overall survival. Therefore, a tailored intense and prolonged follow-up is mandatory.