Initial Chemoradiotherapy Research Articles

Combination chemoradiotherapy with temozolomide, vincristine, and interferon-\u03b2 might improve outcomes regardless of O6-methyl-guanine-DNA-methyltransferase (MGMT) promoter methylation status in newly glioblastoma

BackgroundThis investigator-initiated, open-label, single-arm, single-institute study was conducted to investigate the effectiveness of induction combination chemoradiotherapy and long-term maintenance therapy with temozolomide (TMZ) plus interferon (IFN)-β for glioblastoma.MethodsThe initial induction combination chemoradiotherapy comprised radiotherapy plus TMZ plus vincristine plus IFN-β. Maintenance chemotherapy comprised monthly TMZ, continued for 24–50 cycles, plus weekly IFN-β continued for as long as possible. The primary endpoint was 2-year overall survival (2y-OS). The study protocol was to be considered valid if the expected 2y-OS was over 38% and the lower limit of the 95% confidence interval (CI) was no less than 31.7% compared with historical controls, using Kaplan-Meier methods. Secondary endpoints were median progression-free survival (mPFS), median OS (mOS), 5-year OS rate (5y-OS), and mPFS and mOS classified according to MGMT promoter methylation status.ResultsForty-seven patients were analyzed. The 2y-OS was 40.7% (95%CI, 27.5–55.4%). The mPFS and mOS were 11.0 months and 18.0 months, respectively, and 5y-OS was 20.3% (95%CI, 10.9–34.6%). The mPFS in groups with and without MGMT promoter methylation in the tumor was 10.0 months and 11.0 months (p = 0.59), respectively, and mOS was 24.0 months and 18.0 months (p = 0.88), respectively. The frequency of grade 3/4 neutropenia was 19.1%.ConclusionsThe 2y-OS with induction multidrug combination chemoradiotherapy and long-term maintenance therapy comprising TMZ plus IFN-β tended to exceed that of historical controls, but the lower limit of the 95%CI was below 31.7%. Although the number of cases was small, this protocol may rule out MGMT promoter methylation status as a prognostic factor.Trial registrationUniversity Hospital Medical Information Network (number UMIN000040599).

Tumor Volume Predicts High-Risk Patients and Guides Initial Chemoradiotherapy for Early Cervical Cancer.

We evaluated the relationship between the minimum tumor-free margin, tumor volume, and adverse pathological risk factors in early cervical cancer and explored the predictive value of these parameters for different types of risk patients to guide individualized therapeutic strategies. Patients who received the initial treatment of radical operation of cervical cancer and their postoperative pathological reports in our hospital from July 1, 2017, to June 30, 2019, were reviewed. Their minimum tumor-free margin and tumor volume were measured on preoperative magnetic resonance imaging. Student’s t-test and the receiver operating characteristic curve analysis were used for data analysis. A total of 240 patients were included. Adverse pathological risk factors were as follows: deep cervical infiltration, 95 (39.6%) cases; lymph vascular space invasion, 91 (37.9%); lymph node metastasis, 20 (8.3%); parametrial infiltration, 8 (3.3%); tumor diameter ≥4 cm, 7 (2.9%); and positive surgical margin, 1 (0.4%). According to the adverse pathological factors, there were 20 (8.3%) high-risk patients, 50 (20.8%) medium-risk patients, and 170 (70.8%) low-risk patients. The ranges of the minimum tumor-free margin and tumor volume were 0.01–13.5 mm and 105–27,990 mm3, respectively. The minimum tumor-free margin with lymph node metastasis was significantly smaller than that without (P <0.05). The tumor volume with parametrial infiltration, deep cervical infiltration, or lymph vascular space invasion was significantly greater than that without (P < 0.05). The tumor volume was significantly different among low-, medium-, and high-risk patients (P <0.05). Tumor volume was of predictive value for high-risk patients (P < 0.05). With 3,505 mm3 as the cutoff value, the sensitivity and specificity for the prediction of high-risk patients were 88.9% and 84.8%, respectively. Tumor volume can be used as a great predictor of high-risk patients (cutoff value, 3,505 mm3), which could be an indication of initial chemoradiotherapy for early cervical cancer.

Salvage surgery after definitive chemoradiotherapy for patients with non-small cell lung cancer.

Definitive chemoradiotherapy (CRT) has been a standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). However, locoregional recurrence occurs in about 30% of patients after definitive CRT. Recently, the addition of durvalumab as maintenance therapy has shown to improve the outcome of these patients. However, locoregional recurrence will still remain. “Salvage surgery” has been performed to achieve local control in clinical practice, although its clinical significance is unclear. In this review, we define salvage surgery as lung resection for local control of the tumor which was not planned initially, after failure or insufficient treatment effect of the initial CRT for locally advanced cancer and evaluated nine studies to gain some insights on its role in the treatment of lung cancer. The time from radiotherapy (RT) to salvage surgery varied considerably (range, 3 to 282 weeks). Salvage surgery was performed for persistent disease (47%) and locoregional recurrence (52%). Lobectomy (63%) and mediastinal lymph node dissections (90%) were the most common procedures. However, the rate of pneumonectomy was higher in salvage surgery (28%) compared to that in lung resection in general. The median morbidity was 41% (range, 15% to 62%) and the mortality was 4% (range, 0 to 11%) which appeared acceptable. The median recurrence-free survival and overall survival (OS) after salvage surgery ranged from 10 to 22 months and 13 to 76 months, respectively. Favorable prognostic factors of salvage surgery were longer period from RT to salvage surgery and radiological downstaging. The pathological response was also prognostic, although this information cannot be obtained preoperatively. We conclude that salvage surgery can be considered especially for those with late local recurrence or those with the metabolic response. Given the condition where phase III trials are difficult, the accumulation of real-world evidence in a prospective fashion will be necessary.

GCT-31. DIAGNOSTIC CAPABILITY OF CSF-PLAP ON INTRACRANIAL GERM CELL TUMOR

BACKGROUNDSince the majority of intracranial germ cell tumor(GCT) is sensitive for chemoradiation, biopsy specimens are usually tiny and not enough for accurate pathological diagnosis. To supply complementary diagnostic information, a-fetoprotein or human chorionic gonadotropin-b are important biomarkers. Recently CSF-placental alkaline-phosphatase(PLAP) is also reported as an additional biomarker in intracranial GCT. This study’s purpose is to evaluate the significance of CSF-PLAP.METHODSCSF-PLAP was obtained from the patients with the intraventricular and periventricular tumor before any adjuvant therapy. Definitive diagnoses were made by histopathological information and/or their clinical courses; GCT(germinoma or non-germinomatous GCT(NGGCT)) or other tumors. In GCT, the relationship between CSF-PLAP and tumor reduction volume was evaluated. Tumor volumes were calculated on gadolinium-enhanced T1-weighted magnetic resonance imaging before and after initial chemoradiotherapy.RESULTSBetween 2005 and 2019, 42 patients were studied: 24 with GCT and 18 with others. CSF-PLAP value in patients with GCT was significantly higher than those with others: the Specificity was 88% and the sensitivity was 95% at the cutoff value of 8.0 pg/ml. For GCT patients, CSF-PLAP value tended to be higher in germinoma(n=12, mean 4756 pg/ml), compared to the value in NGGCT(n=7, mean 332 pg/ml), although there was no statistical difference. There was a significant positive correlation between initial CSF-PLAP value and tumor reduction volume.CONCLUSIONCSF-PLAP is a useful tumor marker for GCT differentiating from the other tumors located in intraventricular and periventricular region and CSF-PLAP value might correlate with the volume of germinomatous component of the tumor.

NI-11 Clinical significance of intracystic diffusion hyperintensity lesions remaining after treatment of intracranial germ cell tumor

Background and purpose: About 30% of intracranial germ cell tumors are mixed germ cell tumors and teratomas are often found as those components. Intense chemoradiotherapy is performed according to the malignancy of the histopathology, but high-intensity lesion inside the cystic tumor on diffusion weighted imaging (DWI) sometimes remains after completion of the chemoradiotherapy. In this study, we examined the clinical significance of the DWI high-intensity lesion remaining in the cyst. METHODS: Five patients after initial chemoradiotherapy were resected residual tumor by craniotomy at our hospital from 2009 to 2019. Preoperative gadolinium-enhanced MRI defined the non-contrast-enhanced part of the tumor as intracystic, and DWI intensity was classified by its look as low-intensity, equal-intensity, and high-intensity compared to the cortex of the same slice. DWI signals in the solid area, cyst wall, and cyst were evaluated. Results: All cases were mature teratoma in histopathology, and no other tumor components were observed. On DWI, the cyst wall and solid part were visualized with low signal. High-intensity lesions and equal-intensity lesions in the cyst cavity were found in 3 and 1 cases, respectively. In these cases, pathological findings revealed a keratin-like substance in the cyst. Discussion: The intracystic high and equal intensity lesions on DWI removed after completion of chemoradiotherapy are considered to reflect the keratin-like component of mature teratoma. If DWI- high intensity and equal intensity lesions remain in the cyst of the tumor after the completion of chemoradiotherapy, tumor shrinkage cannot be expected even if the chemotherapy is strengthened. In such cases, we should consider to removing them by surgery. Conclusion: When DWI high and equal intensity lesions are found in the cysts of tumors remaining after chemoradiotherapy for intracranial germ tumors, it is possible that mature teratoma remains.

Re-irradiation with or Without Chemotherapy for In-field Local Recurrence among Esophageal Cancer Patients after Initial Definitive Concurrent Chemo-radiotherapy

Re-irradiation with or Without Chemotherapy for In-field Local Recurrence among Esophageal Cancer Patients after Initial Definitive Concurrent Chemo-radiotherapy

Evaluation of a National Comprehensive Cancer Network Guidelines–Based Decision Support Tool in Patients With Non–Small Cell Lung Cancer

The association of guideline-based decision support with the quality of care in patients with non-small cell lung cancer (NSCLC) is not known. To evaluate the association of exposure to the National Comprehensive Cancer Center (NCCN) guidelines with guideline-concordant care and patients' decisional conflict. A nonrandomized clinical trial, conducted at a tertiary care academic institution, enrolled patients from February 23, 2015, to September 28, 2017. Data analysis was conducted from July 19, 2019, to April 22, 2020. A cohort of 76 patients with NSCLC seen at diagnosis or disease progression and a retrospective cohort of 157 patients treated before the trial were included. Adherence to 6 NCCN recommendations were evaluated: (1) smoking cessation counseling, (2) adjuvant chemotherapy for patients with stage IB to IIB NSCLC after surgery, (3) pathologic mediastinal staging in patients with stage III NSCLC before surgery, (4) pathologic mediastinal staging in patients with stage III NSCLC before nonsurgical treatment, (5) definitive chemoradiotherapy for patients with stage III NSCLC not having surgery, and (6) molecular testing for epidermal growth factor receptor and anaplastic lymphoma kinase alterations for patients with stage IV NSCLC. Subgroup analysis was conducted to compare the rates of guideline concordance between the prospective and retrospective cohorts. Secondary end points included decisional conflict and satisfaction. An online tool customizing the NCCN guidelines to patients' clinical and pathologic features was used during consultation, facilitated by a trained coordinator. Concordance of practice with 6 NCCN treatment recommendations on NSCLC and patients' decisional conflict. Of the 76 patients with NSCLC, 44 were men (57.9%), median age at diagnosis was 68 years (interquartile range [IQR], 41-87 years), and 59 patients (77.6%) had adenocarcinoma. In the retrospective cohort, 91 of 157 patients (58.0%) were men, median age at diagnosis was 66 years (IQR, 61-65 years), and 105 patients (66.9%) had adenocarcinoma. After the intervention, patients received more smoking cessation counseling (4 of 5 [80.0%] vs 1 of 24 [4.2%], P < .001) and less adjuvant chemotherapy (0 of 7 vs 7 of 11 [63.6%]; P = .012). There was no significant change in mutation testing of non-squamous cell stage IV disease (20 of 20 [100%] vs 48 of 57 [84.2%]; P = .10). There was no significant change in pathologic mediastinal staging or initial chemoradiotherapy for patients with stage III disease. After consultation with the tool, decisional conflict scores improved by a median of 20 points (IQR, 3-34; P < .001). The findings of this study suggest that exposure to the NCCN guidelines is associated with increased guideline-concordant care for 2 of 6 preselected recommendations and improvement in decisional conflict. ClinicalTrials.gov Identifier: NCT03982459.

Prognostic factors for patients with limited-stage small-cell lung cancer without receiving prophylactic cranial irradiation

ObjectiveThis retrospective study aims to explore the risk factors for brain metastasis and the prognostic factors for overall survival (OS) in patients with limited-stage small-cell lung cancer (LS-SCLC) who have no brain metastases according to magnetic resonance imaging (MRI) and have not received prophylactic cranial irradiation (PCI) after first-line chemoradiotherapy. MethodsA total of 107 patients who were treated in the Fourth Hospital of Hebei Medical University from January 2013 to December 2017 were enrolled in this study. The patients were treated with etoposide/platinum chemotherapy and thoracic radiotherapy (TRT) with involved-field irradiation. The median dose of the radiotherapy was 60 ​Gy (50−64 ​Gy). The primary study endpoints include BMFS (brain-metastasis-free survival) and OS (overall survival). The Kaplan-Meier method was applied to estimate survival, with a log-rank test used to ascertain statistical significance. The multivariate Cox proportional hazards model was used to determine the prognostic factors for survival. ResultsThe median follow-up of all patients was 18.8 months (range: 7.9–65.1 months) and the median follow-up of surviving patients was 26.7 months (range: 18.8–65.1 months). The median OS of the whole cohort was 20.1 months, and the 1-, 2- and 3-year OS rates were 84.9%, 44.9%, and 25.9%, respectively. The 1-, 2-, and 3-year BMFS rates were 69.0%, 49.9%, and 40.7%, respectively. 50 patients (46.7%) developed brain metastases during the follow-up period, and the median time from the start to brain metastasis was 10.7 months (range: 4.8–31.1 months). As shown by multivariate analysis, independent prognostic factors of OS included cycles of chemotherapy (P ​= ​0.019), the response to initial treatment (P ​= ​0.011), and the start time of TRT (P ​= ​0.044). The independent prognostic factors of BMFS included the clinical stage (P ​= ​0.008), the response to initial treatment (P ​= ​0.024), and the start time of TRT (P ​= ​0.028). ConclusionsFor patients with LS-SCLC who have not received PCI, favorable factors for lower brain metastasis and higher survival include early clinical stage, CR to initial chemoradiotherapy, early TRT, and adequate cycles of chemotherapy. PCI is still recommended as the standard modality since the incidence of brain metastases was high (46.7%).

Ketorolac use and anastomotic leak in patients with esophageal cancer

ObjectivesRecent evidence has shown an association between postoperative ketorolac use and anastomotic leak in patients undergoing intestinal and colorectal operations, but this relationship has been minimally explored after esophagectomy. As the use of nonopioid pain control and enhanced recovery protocols is increasingly prioritized, determination of a possible correlation between perioperative ketorolac use and leak is essential. MethodsRecords of patients undergoing esophagectomy for adenocarcinoma at a single institution from 2006 to 2018 reviewed for occurrence of anastomotic leak. Institutional pharmacy records were queried for ketorolac administration during the surgical case through the time of discharge. Multivariable logistic regression was used to determine the relationship between ketorolac administration and anastomotic leak. ResultsA total of 1019 patients met inclusion criteria, the majority of whom were male (907, 89%) with a median age of 62 years. Patients predominantly presented with locoregionally advanced disease and were treated with initial chemoradiation. Ketorolac was administered to 686 patients (67%); use was observed to increase over the study period from 49% in 2006 to 92% in 2016. Conversely, anastomotic leak occurred in 87 patients (9%) overall and decreased over time from 15% (11/72) in 2006 to 2% (2/83) in 2018. Upon multivariable analysis, neither ketorolac administration evaluated as a categoric variable (odds ratio, 0.99; P = .958) or as a continuous variable using dose (odds ratio, 1.00; P = .843) demonstrated an association with anastomotic leak. ConclusionsKetorolac in the postoperative period after esophagectomy has become an integral component of enhanced recovery pathways and does not appear to be associated with anastomotic leak.

A Phase II Trial of Stereotactic Ablative Radiation Therapy as a Boost for Locally Advanced Cervical Cancer

Our purpose was to assess the feasibility, safety, and efficacy of stereotactic ablative radiation therapy (SAbR) as an alternative for intracavitary/interstitial brachytherapy boost for locally advanced cervical cancer (LACC) after initial chemoradiation. A single arm institutional phase II study of SAbR as a boost for LACC was conducted. Eligible patients had LACC FIGO 2009 stage IB2-IVB, performance status 0 to 3, and one of the following: medically unfit or refused intracavitary or tumor extent required interstitial brachytherapy for coverage. The cervix planning target volume boost (PTVboost) received 28 Gy in 4 fractions. The study was closed with 15 of 21 patients completed owing to concern for toxicity. Median follow-up for this cohort was 19 months. Patients had predominantly advanced stage (III-IV, 53%) with median Charlson comorbidity score of 4. Most tumors were large with a median SAbR boost PTV size of 139 cc (range, 51-268 cc). Tumor size and patient comorbidities probably contributed to the lower-than-expected 2-year local control, progression free, and overall survival of 70.1%, 46.7%, and 53.3%, respectively. The SAbR boost 2 year cumulative grade ≥ 3 toxicity of 26.7% was predominantly rectal (ulcer/fistula).The median SAbR PTV volume was 225 cc versus 95 cc for patients with and without grade ≥ 3 toxicity. On dosimetric analysis, only the percentage of rectal circumference receiving 15 Gy (PRC15) for the SAbR boost was associated with development of grade 3 ulcer or rectovaginal fistula (P = .04), with PRC15 > 62.7% being the strongest predictor of toxicity (AUC, 0.93; sensitivity, 100%; specificity, 90%). In this SAbR boost series suboptimal outcomes were probably related to patient selection and very large tumor volume. This approach may still be considered in patients with smaller tumors unable to undergo standard brachytherapy for cervix cancer.

Real-world experience with Temozolomide &amp; Sativex in patients with recurrent High Grade Gliomas

Abstract Background Glioblastoma (GBM) is the most common malignant brain tumour in adults with a median survival from progression of 8 months. A recent phase 1 study of temozolomide (TMZ) and 1:1 CBD:THC (Sativex) offers evidence of efficacy in patients with recurrent GBM (NCT01812603). Methods All patients receiving TMZ &amp; Sativex (75mg/m2 daily d1 – 21 q28; Sativex continuously) for relapsed GBM or grade 3 astrocytoma at our centre were identified. Patient, tumor and treatment characteristics were recorded, and response based on sequential MRI scans using modified RANO criteria assessed. Results 13 patients were treated over 18 months. The median age was 56; 69% were male. All had received initial chemo-radiotherapy (12 patients: 60 or 59.4Gy/30–33#; 1 patient: 45Gy/15#). 6 patients underwent reresection at recurrence. 4 patients were treated at first progression, 7 at second progression, and 2 at third or later progression. The median number of cycles of TMZ and sativex was 2. The combination treatment was tolerated well by all patients treated, with no Grade 3 or 4 toxicities, the only complaints being of discomfort in mouth after spray and ‘spaced out feeling’. Patients stopped treatment due to evidence of progressive disease on sequential MRI sign or physical deterioration. Median Overall Survival (OS) from initiation was 5.9 months (177 days); Progression Free Surival (PFS) at 3 months was 50%. Conclusion These results highlight some discrepancies in OS in comparison to the previous trial (NCT01812603), but our patients were treated at second/ third recurrence. We agree that the combination is well tolerated.

Prophylactic cranial irradiation in small cell lung cancer: a systematic review and meta-analysis

BackgroundThe efficacy of prophylactic cranial irradiation (PCI) in treating patients with small cell lung cancer (SCLC) has not been clear, and recent randomized studies have demonstrated conflicting results from previously published findings. The purpose of this study was to reevaluate the efficacy of PCI in patients with SCLC and to assess factors associated with its efficacy.MethodsWe conducted a quantitative meta-analysis to explore the efficacy of PCI in patients with SCLC. A literature search was performed using EMBASE, MEDLINE, Cochrane and ClinicalTrials.gov databases. We pooled the data and compared overall survival (OS) and brain metastasis (BM) between patients treated with PCI (PCI group) and patients without PCI treatment (observation group).ResultsOf the 1074 studies identified in our analysis, we selected seven studies including 2114 patients for the current meta-analysis. Our results showed that the PCI group showed decreased BM (HR = 0.45, 95% CI: 0.38–0.55, P < 0.001) and prolonged OS (HR = 0.81, 95% CI: 0.67–0.99, P < 0.001). However, in terms of OS, the pooled analysis showed a high heterogeneity (I2 = 74.1%, P = 0.001). In subgroup analyses of OS, we found that the heterogeneity mainly came from patients with brain imaging after initial chemoradiotherapy (HR = 0.94, 95% CI: 0.74–1.18, P = 0.59).ConclusionsThe results of this study showed that PCI has a significant effect on decreasing BM but little benefit in prolonging OS when brain imaging was introduced to confirm lack of BM after initial chemoradiotherapy and before irradiation.

A Case of Hypopituitarism Diagnosed 13 Years After the Initial Chemoradiation Therapy for Nasopharyngeal Carcinoma

A Case of Hypopituitarism Diagnosed 13 Years After the Initial Chemoradiation Therapy for Nasopharyngeal Carcinoma

28 An MRI radiomic signature for predicting brachytherapy outcomes in locally advanced cervical cancer

Introduction The standard treatment of locally advanced cervical cancer (LACC) consists of concomitant chemoradiation followed by brachytherapy. The recent implementation of image-guided adaptive brachytherapy (IGABT) has shown a significant improvement in local control while limiting toxicity. We identified a radiomic signature of LACC relapse based on per-brachytherapy MRI. Methods 100 patients with LACC treated with pulsed-dose-rate IGABT after initial chemoradiation were retrospectively included (TS: N = 60, training; VS: N = 40, validation). Using LIFEx, we extracted 30 textural features from the clinical target volume delineated on T2 FSE MRI. A methodological study was carried out to identify the most robust and informative features. The ability of remaining features to predict relapse was assessed through univariate and multivariate statistical analysis. Results 9 clusters including 24 robust features were considered for the clinical analysis. In univariate analysis, five features were statistically significant predictors of overall recurrence (TS: p 0.05). A 5-feature signature predicting relapse was identified and validated (TS: AUC = 0.88, p 0.00001, VS: AUC = 0.78, p 0.01) and performed better than the five features determined from univariate analysis and the tumor volume (TS, Delong’s test, p 0.05). Conclusion Our radiomics signature has been validated in an institutional cohort. MRI-based texture analysis could provide clinically relevant information to adapt brachytherapy planning. However, standardization of MRI protocols or development of normalization methods is still needed to perform multi-center MRI-based radiomics studies.

Session 2: Are we ready for primary chemotherapy in rectal cancer: who, when, why?

The potential of preoperative chemotherapy in rectal cancer is the subject of investigation in a number of global randomized trials. In this overview and expert discussion, Professor Cervantes summarizes the findings of numerous Phase II trials testing neoadjuvant chemotherapy. The crucial points in the next phase of trials include: patient selection, whether radiotherapy can be omitted altogether and whether chemotherapy can be used to augment the initial response to chemoradiotherapy. Finally, with the emergence of Magnetic Resonance Tumour Regression Grade a reliable method for assessing response after initial chemoradiotherapy, we ask if this can be used to drive the use of further selective chemotherapy to augment response.

PCN239 - Clinical Characteristics, Treatment Patterns, And Health Care Resource Utilization In Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: A Medical Record Review Study In The United States And Canada

To describe real-world clinical characteristics, treatment patterns, and health care resource utilization in patients who did not experience disease progression during their first two cycles of chemoradiation for unresectable, locally advanced, stage III non-small cell lung cancer (NSCLC) in the United States (US) and Canada. A retrospective review of medical records of patients diagnosed with unresectable, locally advanced, stage III NSCLC was conducted in the US and Canada. Eligible patients were aged ≥18 years and completed at least two cycles of concurrent, platinum-based chemoradiation between January 1, 2011, and March 31, 2016, without experiencing disease progression. The start date of the third cycle or 3 weeks following the end of the second cycle defined the index date. Among 135 patients in the US and 39 patients in Canada, 68.2% (US) and 69.2% (Canada) were male; 71.9% (US) and 84.6% (Canada) were white. In the US and Canada, adenocarcinoma was the most common tumor type (71.9% and 48.7%, respectively), followed by squamous cell carcinoma (25.9% and 30.8%, respectively). Only 7.7% (Canada) and 15.6% (US) received programmed cell death ligand-1 (PD-L1) testing at initial diagnosis. At the index date, the median age was 62.7 (US) and 60.7 (Canada) years; 88.9% (US) and 51.3% (Canada) had a performance status of 0 or 1. The most frequently administered initial chemoradiation regimens were carboplatin and paclitaxel (US, 31.9%), cisplatin and etoposide (US, 24.4%; Canada, 33.3%), and carboplatin (Canada, 20.5%). The median number of cycles administered was 2 in the US and 3 in Canada. Of the 46.7% (US) and 12.8% (Canada) who received additional treatment for stage III disease after chemoradiation, 82.5% (US) and 40.0% (Canada) received chemotherapy. Patients treated with concurrent chemoradiation generally initiated treatment according to guidelines. PD-L1 testing is uncommon.

Natural products: a hope for glioblastoma patients.

Glioblastoma (GBM) is one of the most aggressive malignant tumors with an overall dismal survival averaging one year despite multimodality therapeutic interventions including surgery, radiotherapy and concomitant and adjuvant chemotherapy. Few drugs are FDA approved for GBM, and the addition of temozolomide (TMZ) to standard therapy increases the median survival by only 2.5 months. Targeted therapy appeared promising in in vitro monolayer cultures, but disappointed in preclinical and clinical trials, partly due to the poor penetration of drugs through the blood brain barrier (BBB). Cancer stem cells (CSCs) have intrinsic resistance to initial chemoradiation therapy (CRT) and acquire further resistance via deregulation of many signaling pathways. Due to the failure of classical chemotherapies and targeted drugs, research efforts focusing on the use of less toxic agents have increased. Interestingly, multiple natural compounds have shown antitumor and apoptotic effects in TMZ resistant and p53 mutant GBM cell lines and also displayed synergistic effects with TMZ. In this review, we have summarized the current literature on natural products or product analogs used to modulate the BBB permeability, induce cell death, eradicate CSCs and sensitize GBM to CRT.

Efficacy of prophylactic cranial irradiation in patients with limited-disease small-cell lung cancer who were confirmed to have no brain metastasis via magnetic resonance imaging after initial chemoradiotherapy.

BackgroundProphylactic cranial irradiation (PCI) is recommended for patients with limited-disease small-cell lung cancer (LD-SCLC) who achieved good response to definitive chemoradiotherapy. However, most clinical studies lacked brain imaging scans before PCI. Our study aimed to investigate whether PCI has a survival benefit in patients who have no brain metastases (BM) confirmed via magnetic resonance imaging (MRI) before PCI.ResultsEighty patients were included in this study. Sixty patients received PCI (PCI group) and 20 patients did not (non-PCI group). OS was not significantly different between the two groups. The median OS time was 4.3 years (95% CI: 2.6 years–8.6 years) in the PCI group and was not reached (NR) (95% CI: 1.9 years–NR) in the non-PCI group (p = 0.542). Moreover, no differences were observed in the 3-year rates of PFS (46.2% and 44.4%, p = 0.720) and cumulative incidence of BM (24.0% vs. 27%, p = 0.404).ConclusionsOur result suggests that PCI may not have a survival benefit in patients with LD-SCLC confirmed to have no BM after initial therapy, even if patients achieve a good response to definitive chemoradiotherapy.Patients and MethodsWe retrospectively evaluated patients with LD-SCLC who were confirmed to have no BM via MRI after initial chemoradiotherapy at the Shizuoka Cancer Center between September 2002 and August 2015. The overall survival (OS), progression-free survival (PFS), and cumulative incidence of BM were estimated using the Kaplan–Meier method between patients who received PCI and those who did not. Propensity score matching was used to balance baseline characteristics.

Favorable versus unfavorable prognostic groups by post-chemoradiation FDG-PET imaging in node-positive esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy.

Our purpose was to examine the prognostic value of post-CRT PET based on the presence or absence of FDG-avid metastatic lymph node(s) and metabolic response of the primary tumor in patients with clinically node-positive ESCC treated with definitive chemoradiotherapy (dCRT). We identified 108 eligible patients treated by chemoradiotherapy (CRT) with or without resection from our prospectively collected database. Absence of FDG-avid metastatic lymph node with at least partial response of the primary tumor on PET scan after initial CRT was defined as the Post-CRT PET favorable group (yPET-F), and otherwise as unfavorable group (yPET-U). The Kaplan-Meier method and Cox regression were performed for survival analyses and multivariable analysis, respectively. The study cohort was comprised of 59 patients receiving dCRT. Forty-five patients receiving trimodality therapy (TMT) comprised the comparative group and four patients were excluded from further analyses for developing interval distant metastasis detected on post-CRT PET scan. The median follow-up for the study cohort was 41months. On K-M analysis of the study cohort, yPET-F was found to have significantly better OS (2-year: 72.5% vs 13.7%, p < 0.01) and DMFS (2-year: 71.6% vs 36.6%, p = 0.01) than yPET-U. In multivariable analysis, yPET-F remained as a strong independent favorable prognosticator on both OS (HR 0.08, p < 0.01) and DMFS (HR 0.14, p = 0.02) for the dCRT cohort. Compared with TMT cohort, for yPET-U patients, TMT had better OS (p = 0.03) than dCRT-Operable and dCRT-Operable had superior OS (p = 0.04) than dCRT-Unresectable. For yPET-F patients, there was no difference in both OS (p > 0.99) and DMFS (p = 0.92) between these three groups. Absence of FDG-avid metastatic lymph node with at least partial response of the primary tumor on PET scan after CRT (i.e., yPET-F status) prognosticate for excellent OS and DMFS in cN+ ESCC patients treated with dCRT, and might be comparable to TMT.

MS 11.05 Definitive Chemoradiotherapy in Superior Sulcus Tumor

Superior sulcus tumors have been long defined as a distinct clinical entity. Symptoms including Horner’s syndrome and other neurologic findings as well as severe shoulder pain and SVC syndrome characterize this disease. Early on, the use of preoperative therapy was recognized as potentially useful. Over time, initial chemoradiotherapy followed by surgery has emerged as standard of care for patients with T3 or T4 lesions and N0 or N1 disease. 3-year survival rates of approximately 60% have been reported for surgically resectable patients with advanced disease.