Neoadjuvant Concurrent Chemoradiotherapy Research Articles

Outcomes of neoadjuvant concurrent chemoradiotherapy followed by surgery for non-small-cell lung cancer with N2 disease

ObjectivesThe objective of this study was to evaluate the treatment outcomes and prognostic factors of neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgical resection for non-small cell lung cancer (NSCLC) with N2 disease. Materials and methodsA retrospective review of patients with N2 disease who underwent neoadjuvant CCRT followed by surgery at our institution was performed and multivariate Cox regression analysis was used to determine the factors associated with survival outcomes. ResultsFrom 1997 to 2013, 574 patients underwent curative-intent surgery after neoadjuvant CCRT for NSCLC with N2 disease. The mean age was 59 years (444 men, 77%). The extent of surgery included lobectomy in 418 patients (73%), pneumonectomy in 73 (13%), and sleeve resection in 25 (4.3%). Complete resection was obtained in 543 patients (95%). Postoperative complications and in-hospital mortality occurred in 199 patients (35%) and 21 (3.7%), respectively. Pathologic complete response was achieved in 72 patients (13%) and 304 (53%) experienced mediastinal clearance. With a mean follow-up of 36 months, median overall survival (OS) and recurrence-free survival (RFS) were 56 months and 18 months, respectively. The 5-year OS rates were 61% in ypN0, 49% in ypN1, and 35% in ypN2 (p=0.001). The 5-year RFS rates were 45% in ypN0, 23% in ypN1, and 17% in ypN2 (p<0.001). Older age, advanced pT stage, persistent N2, large cell carcinoma, and pneumonectomy were independent prognostic factors associated with worse OS and poorer RFS. ConclusionNeoadjuvant CCRT followed by surgery could be performed with acceptable early postoperative outcomes, satisfactory local control, and encouraging long-term survival. Care should be taken in selecting patients when necessitating pneumonectomy after neoadjuvant CCRT. Further efforts to improve outcomes in patients with persistent N2 disease are required.

Survival analysis of patients with advanced-stage nasopharyngeal carcinoma according to the Epstein-Barr virus status.

PurposeThe main aim of this study is to analyze the prognostic differences in nasopharyngeal carcinoma (NPC) patients who are positive and negative for Epstein-Barr virus (EBV).ResultsOf the 1106 patients, 248 (22.4%) had undetectable pre-treatment plasma EBV DNA levels. The total distant metastasis rate for EBV-negative group vs. EBV-positive group were 3.6% (9/248) vs. 15.0% (128/858) (P < 0.001). The estimated 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) for EBV-negative group vs. EBV-positive group were 88.9% vs. 76.9% (P < 0.001), 93.6% vs. 85.9% (P = 0.001), 96.7% vs. 84.8% (P < 0.001) and 94.1% vs. 90.0% (P = 0.1), respectively. Multivariate analysis revealed that the EBV status was an independent prognostic factor for DFS (HR, 1.813; 95% CI, 1.219-2.695; P = 0.003), OS (HR, 1.828; 95% CI, 1.075-3.107; P = 0.026) and DMFS (HR, 3.678; 95% CI, 1.859-7.277; P <0.001), and overall stage still remained the most important prognostic factor in patients with stage III-IVB NPC.Methods and MaterialsData on 1106 patients with non-metastatic, histologically proven advanced-stage (III-IVB) NPC who underwent intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Patient survival between different EBV status groups were compared.ConclusionsEBV status was an independent prognostic factor for patients with stage III–IVB NPC. Neoadjuvant chemotherapy (NCT) plus concurrent chemoradiotherapy (CCRT) should be better treatment regimen for EBV-positive patients since distant metastasis was the main failure pattern, and CCRT may be enough for EBV-negative patients.

Effect of MRI-guided intensity-modulated radiotherapy with bone marrow protection on hematologic toxicity in patients with rectal cancer undergoing concurrent chemoradiotherapy

Objective To reduce the radiation dose to the hematopoietic bone marrow (hBM) and acute hematologic toxicity (HT) in patients with rectal cancer undergoing intensity-modulated radiotherapy (IMRT). Methods The previously untreated patients with rectal cancer were enrolled in a prospective study. Pelvic magnetic resonance imaging (MRI) was used to determine and delineate the distribution of hBM, and dose limitations were set (V5<95%, V10<90%, V20<80%, V30<65%). The neoadjuvant therapeutic regimen incl uded concurrent IMRT (95% PTV 50 Gy/25 fractions, 2 Gy/fractions), oxaliplatin 50 mg/m2, qw, and capecitabine 1650 mg/m2, 1 fractions/d (twice a day during radiotherapy). Results A total of 35 patients were enrolled and completed the therapeutic regimen. The incidence of grade 2-4 HT was 31.4%; among these patients, 9(26%) experienced leucopenia, 6(17%) experienced neutropenia, 1(3%) experienced erythropenia, and 1(3%) experienced thrombocytopenia. No patients experienced grade ≥3 anemia. The multivariate logistic linear regression analysis showed that hBM-V5 was significantly correlated with the lowest counts of leukocytes (P=0.005), neutrophils (P=0.002), and platelets (P=0.017). Conclusions The radiation dose to the hBM in the pelvis on MRI is significantly correlated with the incidence and severity of acute HT in patients with rectal cancer undergoing neoadjuvant concurrent chemoradiotherapy. Clinical Trial Registry ClinicalTrials.gov, registration number: NCT01863420. Key words: Rectal neoplasms/intensity-modulated radiation therapy; Magnetic resonance; Bone marrow; Hematologic toxicity

The X-linked inhibitor of apoptosis protein is an independent prognostic marker for rectal adenocarcinoma after preoperative chemoradiotherapy.

Rectal cancer (RC) is a common malignancy of the gastrointestinal tract. Preoperative neoadjuvant concurrent chemoradiotherapy (CCRT) is considered an effective treatment as it down-stages advanced RC. X-linked inhibitor of apoptosis protein (XIAP) and survivin participate in the regulation of apoptosis, a key process in carcinogenesis and tumor progression. However, the prognostic value of concomitant expression of XIAP and survivin in RC patients undergoing neoadjuvant CCRT is not well established. Expression of XIAP and survivin proteins was evaluated by immunohistochemical staining of pre-CCRT and post-CCRT specimens of 58 rectal cancer patients. Clinicopathological parameters were also analyzed. In pre-CCRT biopsy specimens, high survivin expression was significantly associated with perineural invasion (p=0.025), metastatic status (p=0.015), and advanced disease stage (I-IV, p=0.025; early vs. late, p=0.047). In post-CCRT surgical specimens, high XIAP expression was significantly associated with age (p=0.037), T stage (p=0.025), disease stage (p=0.019), and tumor regression grade (TRG) (p=0.000). High survivin expression was significantly correlated with T stage (p=0.044), N stage (p=0.028), metastasis (p=0.007), disease stage (p=0.001), and TRG (p=0.033). Pearson correlation calculations showed a positive correlation between XIAP and survivin immunoreactivity (p=0.000). Patients with low XIAP and low survivin expression tended to have significantly longer overall survival (p=0.006 and 0.001, respectively). In multivariable Cox regression analysis, patients with high XIAP, perineural invasion, and advanced stage had significantly shorter overall survival (p=0.000, 0.002 and 0.000, respectively). In conclusion, high expression of XIAP and survivin is associated with advanced stage and poor prognosis. Expression of XIAP is positively correlated with that of survivin. These data suggest that XIAP is an independent prognostic marker and might be considered as therapy target for rectal cancer after neoadjuvant therapy.

Magnitude and Timing of Gross Tumor Volume Response to Neoadjuvant Chemotherapy and Concurrent Chemoradiation in the Treatment of Locally Advanced Nasopharyngeal Carcinoma

Magnitude and Timing of Gross Tumor Volume Response to Neoadjuvant Chemotherapy and Concurrent Chemoradiation in the Treatment of Locally Advanced Nasopharyngeal Carcinoma

MRI Risk Stratification for Tumor Relapse in Rectal Cancer Achieving Pathological Complete Remission after Neoadjuvant Chemoradiation Therapy and Curative Resection.

PurposeRectal cancer patients achieving pCR are known to have an excellent prognosis, yet no widely accepted consensus on risk stratification and post-operative management (e.g., adjuvant therapy) has been established. This study aimed to identify magnetic resonance imaging (MRI) high-risk factors for tumor relapse in pathological complete remission (pCR) achieved by rectal cancer patients who have undergone neoadjuvant concurrent chemoradiation therapy (CRT) and curative resection.Materials and MethodsWe analyzed 88 (male/female = 55/33, median age, 59.5 years [range 34–78]) pCR-proven rectal cancer patients who had undergone pre-CRT MRI, CRT, post-CRT MRI and curative surgery between July 2005 and December 2012. Patients were observed for post-operative tumor relapse. We analyzed the pre/post-CRT MRIs for parameters including mrT stage, mesorectal fascia (mrMRF) status, tumor volume, tumor regression grade (mrTRG), nodal status (mrN), and extramural vessel invasion (mrEMVI). We performed univariate analysis and Kaplan-Meier survival analysis.ResultsPost-operative tumor relapse occurred in seven patients (8.0%, n = 7/88) between 5.7 and 50.7 (median 16.8) months. No significant relevance was observed between tumor volume, volume reduction rate, mrTRG, mrT, or mrN status. Meanwhile, positive mrMRF (Ppre-CRT = 0.018, Ppre/post-CRT = 0.006) and mrEMVI (Ppre-CRT = 0.026, Ppre-/post-CRT = 0.008) were associated with higher incidence of post-operative tumor relapse. Kaplan-Meier survival analysis revealed a higher risk of tumor relapse in patients with positive mrMRF (Ppre-CRT = 0.029, Ppre-/post-CRT = 0.009) or mrEMVI (Ppre-CRT = 0.024, Ppre-/post-CRT = 0.003).ConclusionPositive mrMRF and mrEMVI status was associated with a higher risk of post-operative tumor relapse of pCR achieved by rectal cancer patients, and therefore, can be applied for risk stratification and to individualize treatment plans.

Long-term oncologic outcomes of neoadjuvant concurrent chemoradiotherapy with capecitabine and radical surgery in locally advanced rectal cancer: 10-year experiences at a single institution

PurposeOral capecitabine has demonstrated to be safe and efficient as neoadjuvant concurrent chemoradiotherapy (NCRT) for locally advanced rectal cancers. The aim of this study was to evaluate the long-term oncologic outcomes of NCRT with capecitabine and radical surgery.MethodsFrom January 2000 to June 2010, 238 patients were treated at our center for locally advanced rectal cancers using conventional NCRT with capecitabine and radical surgery. Univariate and multivariate analyses were used to evaluate the factors associated with oncologic outcomes with log rank and Cox regression tests.ResultsThe incidence of grade >3 capecitabine-related toxicity was found to be 4.6%. A pathologic complete response was observed in 14.7% of patients. The 5-year overall and 5-year disease-free survival rate, local and systemic recurrence rate were 82.8%, 75.1%, 4.8%, and 20.3%. Abdominoperineal resection and node-positive disease were independent prognostic factors of 5-year overall survival, 5-year disease-free survival, and systemic recurrence.ConclusionNCRT with capecitabine and radical surgery showed favorable long-term oncologic outcomes with benefits of acceptable toxicity and convenience. We suggest that capecitabine can be one of the favorable therapeutic options for NCRT in rectal cancer.

Pancreatic cancer planning: Complex conformal vs modulated therapies

To compare the roles of intensity-modulated radiation therapy (IMRT) and volumetric- modulated arc therapy (VMAT) therapy as compared to simple and complex 3-dimensional chemoradiotherpy (3DCRT) planning for resectable and borderline resectable pancreatic cancer. In all, 12 patients who received postoperative radiotherapy (8) or neoadjuvant concurrent chemoradiotherapy (4) were evaluated retrospectively. Radiotherapy planning was performed for 4 treatment techniques: simple 4-field box, complex 5-field 3DCRT, 5 to 6-field IMRT, and single-arc VMAT. All volumes were approved by a single observer in accordance with Radiation Therapy Oncology Group (RTOG) Pancreas Contouring Atlas. Plans included tumor/tumor bed and regional lymph nodes to 45Gy; with tumor/tumor bed boosted to 50.4Gy, at least 95% of planning target volume (PTV) received the prescription dose. Dose-volume histograms (DVH) for multiple end points, treatment planning, and delivery time were assessed. Complex 3DCRT, IMRT, and VMAT plans significantly (p < 0.05) decreased mean kidney dose, mean liver dose, liver (V30, V35), stomach (D10%), stomach (V45), mean right kidney dose, and right kidney (V15) as compared with the simple 4-field plans that are most commonly reported in the literature. IMRT plans resulted in decreased mean liver dose, liver (V35), and left kidney (V15, V18, V20). VMAT plans decreased small bowel (D10%, D15%), small bowel (V35, V45), stomach (D10%, D15%), stomach (V35, V45), mean liver dose, liver (V35), left kidney (V15, V18, V20), and right kidney (V18, V20). VMAT plans significantly decreased small bowel (D10%, D15%), left kidney (V20), and stomach (V45) as compared with IMRT plans. Treatment planning and delivery times were most efficient for simple 4-field box and VMAT. Excluding patient setup and imaging, average treatment delivery was within 10minutes for simple and complex 3DCRT, IMRT, and VMAT treatments. This article shows significant improvements in 3D plan performance with complex planning over the more frequently compared 3- or 4-field simple 3D planning techniques. VMAT plans continue to demonstrate potential for the most organ sparing. However, further studies are required to identify if dosimetric benefits associated with inverse optimized planning can be translated into clinical benefits and if these treatment techniques are value-added therapies for this group of patients with cancer.

Abstract A002: Serum biomarkers of VEGF-A and TGF-β1 predict pathological response and survival of esophageal cancer patients treated with neoadjuvant chemoradiotherapy and esophagectomy

Abstract This study is aimed to identify serum biomarkers that predict treatment response and survival by screening proximity ligation assay (PLA) and verified enzyme-linked immunosorbent assay (ELISA) for patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant concurrent chemoradiotherapy (CCRT) followed by esophagectomy. One hundred and three patients with ESCC receiving CCRT consisting of taxane-/5-fluorouracil-based chemotherapy and 40Gy radiotherapy followed by surgery were prospectively enrolled. Serum samples were collected before and within 1 month after completion of CCRT. With the use of PLA, 15 biomarkers were simultaneously analyzed in the initial 79 patients. The biomarkers significantly associated with pathological response (PathR)/survival were verified by ELISA in an expanded group of 103 patients. Associations between serum levels of biomarkers and clinical factors correlating with PathR, disease-free survival (DFS), and overall survival (OS) were evaluated by ANOVA and log-rank tests. Following CCRT, 38 patients had pathologically complete response (37%), 44 microscopic (43%), and 21 macroscopic residual disease (20%). With a median follow-up of 66 months, the median DFS and OS were 23.7 months and 43.5 months, respectively. Among the 15 biomarkers screened by PLA, vascular endothelial growth factor-A (VEGF-A) and transforming growth factor-β1 (TGF-β1) were significantly associated with PathR and/or DFS. These biomarkers were further analyzed by ELISA to confirm initial biomarker findings by PLA. On ELISA, both pre- and post-CCRT VEGF-A levels were significantly correlated with PathR (p=0.042 and 0.019, respectively). Patients with high pre-CCRT VEGF-A/TGF-β1 levels (≥median) had significantly worse median DFS (9.3 months vs. 34.6 months, p=0.007) and worse median OS (26.7 months vs. 51.5 months, p=0.05). On multivariate analysis, PathR (p=0.001) and pre-CCRT high levels (≥median) of both VEGF-A and TGF-β1 (p=0.005) were independent factors for DFS. PathR (p=0.002) was the only significant factor for OS, while pre-CCRT high levels of both VEGF-A and TGF-β1 were borderline significant (p=0.065). In conclusion, serum VEGF-A may be used to predict post-CCRT pathological response. High serum levels of VEGF-A and TGF-β1 before CCRT associate with significantly worse DFS and a trend toward worse OS. Citation Format: Jason Chia-Hsien Cheng, Yun Chiang, Feng-Ming Hsu, Chiao-Ling Tsai, Chih-Hung Hsu, Jang-Ming Lee. Serum biomarkers of VEGF-A and TGF-β1 predict pathological response and survival of esophageal cancer patients treated with neoadjuvant chemoradiotherapy and esophagectomy. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A002.

Predictors of Survival in Esophageal Squamous Cell Carcinoma with Pathologic Major Response after Neoadjuvant Chemoradiation Therapy and Surgery: The Impact of Chemotherapy Protocols.

Tumor recurrence is an important problem threatening esophageal cancer patients after surgery, even when they achieve a pathologic major response (pMR) after neoadjuvant concurrent chemoradiation therapy (CCRT). The predictors related to overall survival and disease progression for these patients remain elusive. We aimed to identify factors that predict disease progression and overall survival in esophageal squamous cell carcinoma (SCC) patients who achieve a pMR after neoadjuvant CCRT followed by surgery. We conducted a retrospective study to analyze the factors influencing survival and disease progression after esophagectomy for esophageal cancer patients who had a major response to CCRT, which is defined by complete pathological response or microscopic residual disease without lymph node metastasis. From our study cohort, 285 patients underwent CCRT and subsequent esophagectomy; 171 (60%) of these patients achieved pMR. After excluding patients with lymph node metastases, incomplete clinical data, and adenocarcinomas, we enrolled 117 patients in this study. We found that the CCRT regimen was the only factor that influenced overall survival. The overall survival of the patients receiving taxane-incorporated CCRT was superior to that of patients receiving traditional cisplatin and 5-fluorouracil (PF) (P = 0.011). The CCRT regimen can significantly influence the clinical outcome of esophageal SCC patients who achieve pMR after neoadjuvant CCRT and esophagectomy. Incorporation of taxanes into cisplatin-based CCRT may be associated with prolonged survival.

Profiling of rectal cancers MRI in pathological complete remission states after neoadjuvant concurrent chemoradiation therapy

To fully characterise the magnetic resonance imaging (MRI) traits of rectal cancers in a large sample of patients, each experiencing pathological complete remission (pCR) after neoadjuvant concurrent chemoradiation therapy (CCRT). A total of 120 patients (77 male, 43 female; median age, 59.5 years; range, 32-81 years) with rectal cancers in CCRT-induced pCR states who underwent pre- and post-CCRT MRI and eventual surgery between July, 2005 and September, 2014 were retrospectively reviewed. In most (n=100), diffusion-weighted imaging was also performed. Tumour volume, tumour regression grade (TRG), T-stage, mesorectal fascia (MRF) status, and T2 signal intensity (T2-SI) were analysed. Paired t-test and McNemar's test were applied for statistical comparisons. Tumour volume declined sharply after CCRT (pre-CCRT, 21.5 ± 22.4 cm(3); post-CCRT, 6.6 ± 8.4 cm(3); p<0.001). TRG distribution was as follows: G1 (clinical CR), 3; G2, 38; G3, 78; G4, 1; and G5 (marked progression), 0. Downstaging of T-stage (34%,16/47) and MRF status (19.7%,13/66) did occur; but on post-CCRT MRI, 25.8% (31/120) remained at T3 ≥ 5 mm or T4 stage, and 44.2% (53/120) were MRF-positive. A majority (88.3%, 106/120) of patients displayed intermediate T2-SI prior to CCRT. Most converted to dark T2-SI after CCRT, with 12.5% (15/120) unchanged. On post-CCRT MRI, 11% (11/100) of patients showed diffusion restriction. MRI findings in CCRT-induced pCR-status rectal cancers were highly variable. Tumour volume and T2-SI mostly decreased; however, such lesions occasionally presented with unexpected atypical features, such as large residual volume and/or intermediate T2-SI.

Cost-effectiveness of neoadjuvant concurrent chemoradiotherapy versus esophagectomy for locally advanced esophageal squamous cell carcinoma: A population-based matched case-control study.

BackgroundNeoadjuvant concurrent chemoradiotherapy (NCCRT) is often considered for locally‐advanced esophageal squamous cell carcinoma (LA‐ESCC) patients; however, no data regarding the cost‐effectiveness of this treatment is available. Our study aimed to evaluate the cost‐effectiveness of NCCRT versus esophagectomy for LA‐ESCC at population level.MethodsWe identified LA‐ESCC patients diagnosed within 2008–2009 and treated with either NCCRT or esophagectomy through the Taiwan Cancer Registry. We included potential confounding covariables (age, gender, residency, comorbidity, social‐economic status, disease stage, treating hospital level and surgeon's experience, and the use of endoscopic ultrasound before treatment) and used propensity score (PS) to construct a 1:1 population. The duration of interest was three years within the date of diagnosis. Effectiveness was measured as overall survival. We took the payer's perspective and converted the cost to 2014 United States dollars (USD). In sensitivity analysis, we evaluated the potential impact of an unmeasured confounder on the statistical significance of incremental net benefit at suggested willingness‐to‐pay.ResultsOur study population constituted 150 PS matched subjects. The mean cost (2014 USD) and survival (year) were higher for NCCRT compared with esophagectomy (US$91,460 vs. $75,836 for cost; 2.2 vs. 1.8 for survival) with an estimated incremental cost‐effectiveness ratio of US$39,060/life‐year.ConclusionsWhen compared to esophagectomy, NCCRT is likely to improve survival and is probably more cost‐effective. Cost‐effectiveness results should be interpreted with caution given our results were sensitive to potential unmeasured confounder(s) in sensitivity analysis.

Changes in tumour expression of programmed death-ligand 1 after neoadjuvant concurrent chemoradiotherapy in patients with squamous oesophageal cancer

BackgroundProgrammed death-ligand 1 (PD-L1) expression has been suggested as a potential predictive biomarker of response to anti-PD-1/PD-L1 therapy. In this study, we investigated whether the expression of PD-L1 in tumour cells is affected by neoadjuvant concurrent chemoradiotherapy (CCRT) or chemotherapy in oesophageal squamous cell carcinoma. Patients and methodsBetween 2004 and 2014, we collected the medical records of locally advanced oesophageal cancer patients consecutively diagnosed and treated with neoadjuvant CCRT or chemotherapy, followed by curative resection. PD-L1 expression in acquired tissue specimens was evaluated by immunohistochemistry using the H-score. The changes in PD-L1 expression between paired samples were evaluated and we also analysed PD-L1 expression in surgical tumour specimens to evaluate its prognostic role. ResultsTwenty-eight paired tumour tissues that were acquired before and after neoadjuvant therapy were available: 19 patients with CCRT and 9 with chemotherapy before complete oesophagectomy. The PD-L1 H-score increased significantly from baseline tumour tissues to surgical tumour tissues after neoadjuvant CCRT (P = 0.007, median H-score from 28 to 52), whereas it decreased significantly after neoadjuvant chemotherapy (P = 0.048, median H-score from 53 to 22). In a total of 73 patients, including 45 additional cases for the prognosis analysis, patients with higher PD-L1 H-scores (≥20) had poorer overall survival (median 16.7 versus 32.9 months, P = 0.02) than those with lower H-scores (<20). ConclusionsPD-L1 expression in tumour cells increased in oesophageal cancer patients who received neoadjuvant CCRT. Further studies with more cases are necessary to validate these findings.

Identification of surrogate endpoints in patients with locoregionally advanced nasopharyngeal carcinoma receiving neoadjuvant chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone.

BackgroundIn the era of intensity-modulated radiotherapy (IMRT), the efficacy of additional neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) is currently being investigated in ongoing trials. Overall survival (OS) is the gold standard endpoint in NPC trials. We performed this analysis to identify surrogate endpoints for OS, which could shorten follow-up duration and speed up assessment of treatment effects.MethodsWe retrospectively analysed 208 matched-pair patients with locoregionally advanced NPC receiving NACT+CCRT or CCRT. Progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) and locoregional failure-free survival (LR-FFS) at 2 and 3 years were assessed as surrogates for 5-year OS according to Prentice’s criteria. The strength of the associations were assessed using Spearman’s rank correlation coefficient.ResultsNo significant differences were observed between treatment arms for any surrogate endpoint at 2 years, which rejected Prentice’s second criterion. In contrast, 3-year LR-FFS, PFS, FFS and D-FFS were consistent with all four of Prentice’s criteria; the rank correlation coefficient (0.730) between 3-year PFS and 5-year OS was highest.Conclusions3-year PFS, FFS and D-FFS could be valid surrogate endpoints for 5-year OS; 3-year PFS may be the most accurate.

Predictors of pathologic complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

Objective To evaluate the potential influencing factors associated with pathologic complete response (pCR) after neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Methods A retrospective analysis was performed on the clinical data 265 patients with stage Ⅱ and Ⅲ(the 7th version of AJCC) rectal cancer admitted to our hospital from 2011 to 2013. All patients underwent neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery with/or without induction chemotherapy during the interval between the complete of CCRT and surgery. The predictors associated with pCR were analyzed by univariate and multivariate logistic regression analyses. With the use of the independent predictive variables for pCR from multivariate analysis, a clinical risk score model was established according to the following criteria: no-risk group (0 factor); low-risk group (1 factor); high-risk group (2 factors). Results Among these 265 patients, 50(18.9%) achieved pCR. The univariate analysis showed that carcinoembryonic antigen (CEA) level before CCRT (P=0.017), T stage before CCRT (P=0.001), interval between complete of CCRT and surgery (P=0.000), and the maximum tumor thickness before CCRT (P=0.040) were significantly associated with pCR. The multivariate analysis showed that pre-CCRT CEA level (P=0.021 or 0.446) and interval between the complete of CCRT and surgery (P=0.000 or 3.774) were significant predictors of pCR. When stratifying for smoking status, only low pre-CCRT CEA level was significantly associated with pCR in the non-smoking patients (P=0.044). For the prediction of pCR by the clinical risk score model, the sensitivity was 0.805, the specificity was 0.460, the area under the receiver operating curve was 0.690(95% CI=0.613-0.767), the positive predictive value was 35.49%, the negative predictive value was 86.5%, and the predictive accuracy was 73.9%. Conclusions For locally advanced rectal cancer, pCR can be achieved in some patients after neoadjuvant therapy. Low pre-CCRT CEA level and long interval time between CCRT and surgery are independent factors associated with pCR, and only low pre-CCRT CEA level is an associated factor in the group of nonsmokers. The clinical risk score model based on pre-CCRT CEA level>5 ng/ml and time interval from CCRT completion to surgery ≤8 weeks can be used to predict pCR after neoadjuvant chemoradiotherapy for LARC. Key words: Rectal neoplasms/neoadjuvant therapy; Pathologic complete response; Factors analysis

Tumor invasion depth is a useful pathologic assessment for predicting outcomes in cervical squamous cell carcinoma after neoadjuvant radiotherapy.

BackgroundTo evaluate whether tumor invasion depth can be a reliable and easily applicable pathologic assessment strategy to predict outcomes using surgically resected cervical squamous cell carcinoma specimens from patients who have received neoadjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT).MethodsWe included 173 patients with cervical squamous cell carcinoma who received neoadjuvant CCRT (n = 125) or RT (n = 48) and underwent subsequent radical hysterectomy. Data for the pre-operative clinical International Federation of Gynecology and Obstetrics (FIGO) stage, post-operative pathologic FIGO stage, World Health Organization (WHO) double diameter measurement evaluation, response evaluation criteria in solid tumors (RECIST 1.1) criteria, tumor necrosis rate (TNR), and tumor regression grade (TRG) were investigated to identify correlations with outcomes related to distant metastasis and survival. The tumor invasion depth (TID) and the tumor invasion depth with cytokeratin immunostaining correction (TIDC) at the cervical internal surface were measured to assess their relations to patients’ outcomes.ResultsBased on measurements taken via transvaginal ultrasound, the pre-operative clinical and post-operative pathologic FIGO staging as well as the WHO double diameter measurement evaluation and RECIST 1.1 criteria were predictive of distant metastasis and survival-related outcomes. Also, lymph node involvement was found to be an independent prognostic factor for recurrence and distant metastasis. Finally, univariate analysis showed both the TID and TIDC were highly related to distant metastasis, overall survival, and progression-free survival, irrespective of the clinical stage of carcinomas.ConclusionThe TID or TIDC measured at the cervical internal surface is a useful and easily applied pathologic prognostic factor for distant metastasis and survival outcomes in patients with cervical squamous cell carcinoma treated with neoadjuvant RT or CCRT.Electronic supplementary materialThe online version of this article (doi:10.1186/s13000-015-0426-6) contains supplementary material, which is available to authorized users.

Magnitude and Timing of GTV Response to Neoadjuvant Chemotherapy and Concurrent Chemoradiation in the Treatment of Locally Advanced Nasopharyngeal Carcinoma

Curative radiation therapy for locally advanced nasopharyngeal carcinoma (NPC) is based on the gross tumor volume (GTV), but the magnitude and timing of GTV changes during combined modality therapy remain unclear. This study analyzes GTV changes at phases of induction chemotherapy and sequential concurrent chemoradiation therapy (CRT) in patients with locally advanced NPC. Subjects include 13 patients with newly diagnosed stage III-IV NPC who underwent treatment between 2011 and 2014. Criteria for eligibility included 2 cycles of neoadjuvant chemotherapy, at least 5 cycles of concurrent chemotherapy and 3 magnetic resonance imaging (MRI) scans at specific phases of treatment (T0: before treatment, T1: postinduction and T3: 3 months after CRT). Induction phase consisted of 2 cycles of gemcitabine and cisplatin. CRT phase consisted of weekly cisplatin and radiation therapy delivered using volumetric modulated arc therapy (VMAT). The total dose was 70 Gy over 35 daily fractions administered 5 days/week. A subset of 3 patients received an additional MRI 4 to 5 weeks into CRT (T2). Gross tumor volume primary (GTVp) was defined as GTV at the primary site and adjacent retropharyngeal LN when involved. GTVp delineated on gadolinium-enhanced fat-saturation T1weighted MRIs by 2 observers and included primary tumor volume and adjacent involved lymph nodes. Mean values are reported ± 1 standard deviation. Preliminary analysis includes 6 (out of 13) patients. The mean initial GTVp was 62.7±32.8 cc. The mean GTVp response after induction phase was 21.4±12.3% with a mean rate of volume change 0.31±0.19 cc/day which corresponds to 0.56±0.35% daily reduction in volume. Total mean GTVp response after completion of treatment (T3) was 77.6±21.6%. Subgroup analysis of subjects who underwent an additional MRI showed a mean GTV reduction of 42.5±22.6% and a mean rate of volume change of 0.87±0.08 cc/day corresponding to 1.7±0.93% daily reduction in volume (from T1 to T2). Preliminary results suggest that the GTV progressively diminishes following both induction chemotherapy and CRT. The mean GTVp response at 4 to 5 weeks into CRT was twofold higher than the response observed after induction chemotherapy. The rate of volume change observed 4 to 5 weeks into CRT exceeded the rate of change during induction phase threefold. These observations may help delineate the optimal timing of imaging and replanning in the context of adaptive field radiation therapy. Analysis of the full NPC patient dataset is ongoing and will be reported.

The influence of neoadjuvant therapy for the prognosis in patients with rectal carcinoma: a retrospective study.

Rectal cancer, defined as a cancerous lesion of the colon distal to the rectosigmoid junction, is the fourth most common cancer cause of death globally. There were 474 patients with rectal cancer who underwent surgery between October 2007 and May 2013 enrolled in our center. Patients were respectively categorized by neoadjuvant therapy. This study aimed to explore the predictive factors that affected the Progression-free survival and overall survival of the patients with rectal cancer. Clinical characteristics of patients were compared with the groups and potential prognostic factors were analyzed by SPSS 19.0. In our study, neoadjuvant therapy increased the anus-retained rate (64.4 vs 53.4% P = 0.016) and remission rate in the treatment group, compared to the non-treatment group (62.6 vs 34.8%; P = 0.000). The neoadjuvant concurrent chemoradiotherapy, more operative duration, anus retained and micturition damaged are positive prognostic factors of PFS to patients. Poor differentiation, the tumor of ulcer, invasive, and pT4 stage, contributed the poor factors for PFS of patients (P < 0.05). Additionally, the patients with neoadjuvant concurrent chemoradiotherapy and adjuvant chemotherapy underwent the better prognosis of OS. Adjuvant chemotherapy cannot increase PFS of the patients who accepted neoadjuvant therapy after surgery get pCR, but can improve OS. The anus-retained and neoadjuvant radiotherapy, duration of surgery in rectal cancer have the positive correlation. Micturition damaged and neoadjuvant radiotherapy were positively correlated as well. In conclusion, adjuvant chemotherapy does not improve the PFS of patients with pCR to neoadjuvant therapy, but is good for OS. Further prospective and large population-based clinical studies are needed to establish clinical guidelines for the use of neoadjuvant therapy and adjuvant chemotherapy in patients with rectal cancer.

Volume-Based Assessment With 18F-FDG PET/CT Improves Outcome Prediction for Patients With Stage IIIA-N2 Non-Small Cell Lung Cancer.

We evaluated the prognostic impact of volume-based assessment by pretreatment (18)F-FDG PET/CT in patients who had clinical stage IIIA-N2 non-small cell lung cancer (NSCLC) treated with neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgical resection. We reviewed 161 consecutive patients who had stage IIIA-N2 NSCLC treated with neoadjuvant CCRT followed by surgery. In all cases, N2 disease was pathologically confirmed by mediastinoscopic biopsy, endobronchial ultrasound-guided transbronchial needle aspiration, or video-assisted thoracoscopic surgery. We measured the total metabolic tumor volume (total MTV) and the maximum standardized uptake value (SUVmax), including a primary tumor and metastatic nodes on the pretreatment scan. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. The association of PET parameters with OS and DFS was determined by univariable and multivariable analyses performed using the Cox regression model. A higher total MTV was significantly associated with poor DFS (hazard ratio [HR], 1.82; p = 0.036) and OS (HR = 2.97; p = 0.012) in the multivariable analysis. In contrast, a higher SUVmax was not significantly associated with poor DFS and OS. Patients with a high total MTV (> 22 cm(3)) had a median survival time that was significantly shorter than that of patients with a low total MTV (median DFS, 11.3 vs 42.0 months, respectively [p < 0.001]; median OS, 38.3 months vs not reached [p < 0.001]). Kaplan-Meier curves showed significant differences on the basis of total MTV in patients with or without mediastinal downstaging after CCRT. Patients with a high total MTV had significantly worse DFS when they had post-neoadjuvant pathologic (yp) stage 0-II disease (p = 0.020) or yp stage III disease (p = 0.036). Higher total MTV was also associated with worse OS in patients with yp stage 0-II disease (p = 0.013) or yp stage III disease (p = 0.007). A higher pretreatment total MTV is associated with worse outcome, independent of yp stage, in patients with stage IIIA-N2 NSCLC treated with neoadjuvant CCRT followed by surgery.

Serum Transforming Growth Factor-β1 Change After Neoadjuvant Chemoradiation Therapy Is Associated With Postoperative Pulmonary Complications in Esophageal Cancer Patients Undergoing Combined Modality Therapy

Our aim was to investigate the association of clinical factors, dosimetric parameters, and biomarkers with postoperative pulmonary complications (PPCs) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated by neoadjuvant concurrent chemoradiation therapy (CCRT) under strict pulmonary dose constraints and esophagectomy. We prospectively enrolled 112 patients undergoing trimodality treatment (including radiation therapy [40 Gy], concurrent taxane-/5-fluorouracil-based regimens, and radical esophagectomy) for ESCC. A PPC was defined as pneumonia or acute respiratory distress syndrome within 30 days after surgery. Serum samples were collected before and within 1 month after CCRT. The association of serum biomarkers with PPCs was detected by proximity ligation assay (PLA) and verified by enzyme-linked immunosorbent assay. Associations of clinical factors, lung dosimetric parameters, and biomarkers with PPC were tested statistically. Thirty-three patients (29.5%) had PPCs. None of the dosimetric parameters was associated with PPCs. Preoperative functional vital capacity (FVC) was significantly associated with PPCs (P=.004). Of the 15 PLA-screened biomarkers, posttreatment transforming growth factor-β1 (TGF-β1) was borderline significantly associated with PPCs (P=.087). Patients with PPCs had significantly larger pre-CCRT to post-CCRT decrease in serum TGF-β1 concentration (-11,310 vs -5332 pg/mL, P=.005) and higher pre-CCRT to post-CCRT percent decline in serum TGF-β1 concentration (-37.4% vs -25.0%, P=.009) than patients without PPCs. On multivariate analysis, preoperative FVC (P=.003) and decrease in TGF-β1 >7040 pg/mL (P=.014) were independent factors associated with PPCs. Preoperative FVC and decrease in serum TGF-β1 level after dose-limited CCRT to the lung are associated with the development of PPCs.