Median Number Of Chemotherapy Cycles Research Articles

Phase II, multicentre, randomised trial of eribulin plus gemcitabine versus paclitaxel plus gemcitabine as first-line chemotherapy in patients with HER2-negative metastatic breast cancer

BackgroundPaclitaxel plus gemcitabine (PG) combination chemotherapy is a preferred chemotherapeutic regimen for patients with metastatic breast cancer (MBC). Eribulin mesylate is a halichondrin non-taxane inhibitor of microtubule dynamics. A recent pooled analysis with eribulin showed improved overall survival (OS) in various MBC patient subgroups pretreated with anthracycline and taxane. Furthermore, eribulin may have less neurotoxicity than paclitaxel. Patients and methodsThis study was a prospective randomised phase II, open-label, two-arm, multicentre study comparing eribulin plus gemcitabine (EG) with PG chemotherapy as a first-line treatment for patients with human epidermal growth factor receptor 2-negative MBC. We hypothesised that EG chemotherapy would not be inferior to PG chemotherapy. The primary end-point was progression-free survival (PFS), which was estimated to be 70% at 6 months for each arm. The secondary end-points were as follows: OS, neuropathic scale, toxicity and clinical benefit rate. ResultsA total of 118 patients (median age: 50, 24–66) were enrolled between March 2015 and March 2016 and were randomly assigned to PG (n = 59) or EG (n = 59) chemotherapy. The mean number of metastatic sites was 3 (range 1–8). The 6-month PFS rates for both arms were 72% for EG and 73% for PG (P = 0.457). There was no significant difference in OS between the two groups (not reached versus 21.2 months, P = 0.2234). The median number of chemotherapy cycles for both groups was 10 for EG and 8 for PG (range 2–32). Clinical benefit rates were 44% for EG and 49% for PG. Major toxicities were neutropenia and neurotoxicity. Grade II or above neurotoxicity was more common with PG than with EG (13.6% for EG versus 45.8% for PG, P < 0.0001). ConclusionEG chemotherapy had similar clinical benefits to PG chemotherapy in terms of PFS but less neurotoxicity. Trial registrationKCSG BR13-11; ClinicalTrials.gov, NCT02263495.

Incidence, clinical characteristics, and outcome of interstitial pneumonia in patients with lymphoma

Interstitial pneumonia (IP) is a lethal complication in lymphoma patients undergoing chemotherapy. A total of 2212 consecutive patients diagnosed with lymphoma between 2009 and 2014 were enrolled in the present study. IP was defined as diffuse pulmonary interstitial infiltrate found on computed tomography scans. IP was observed in 106 patients. Of these, 23 patients were excluded from the study. Finally, 83 patients with IP were included in this study. The incidence of IP was 3.9% (7/287) in Hodgkin lymphoma and 2.4% (76/1925) in non-Hodgkin lymphoma (P = 0.210). The median number of chemotherapy cycles before IP was 3. The median time from the cessation of chemotherapy to IP was 17 days. Eighty-two (98.8%) patients recovered after the treatment with glucocorticoids. Sixty-six (79.5%) patients had a delay in chemotherapy, and 14 (16.9%) patients had premature termination of chemotherapy. Sixty-nine patients were re-treated with chemotherapy after remission from IP, of which 22 (31.9%) experienced IP recurrence. The incidence of IP recurrence was significantly higher in patients re-treated with a similar regimen than in those re-treated with an alternative regimen (65.4 vs. 11.6%, P < 0.001). In a multivariate Cox regression analysis, B symptoms and a history of drug allergies were identified as risk factors for IP. In conclusion, IP is a life-threatening complication in lymphoma patients. Glucocorticoid therapy with continuous monitoring of chest radiographic changes may be a favourable strategy for treating IP. However, IP may recur, especially in patients re-treated with a similar chemotherapy regimen.

Management of Double/Triple Hit Early Stage Diffuse Large B-Cell Lymphoma With Radiation Therapy

The role of consolidative radiation therapy (RT) after R-CHOP in early stage Diffuse Large B-Cell Lymphoma (DLBCL) remains controversial. Further, recent research has identified double-hit (DHL) and triple-hit (THL) as aggressive subtypes of this disease, but the role of RT has not been well defined in these cases. We evaluated the outcome of patients treated with systemic therapy followed by consolidative RT vs. those treated with systemic therapy alone with a focus on DHL and THL. A total of 209 lesions treated in 188 patients with early stage DLBCL were identified for retrospective analysis. These patients were treated in a single institution, from February 1998 to December 2014. Details of clinical characteristics, treatments, outcomes, and molecular profiles were extracted from clinical chart review and radiologic examinations. A total of 141 lesions were treated with RT (67%). Outcomes including time to relapse (TTR) and overall survival (OS) were estimated with Kaplan-Meier rates. Univariate (UVA) and multivariate (MVA) Cox proportional hazard ratios (HR) were used to assess the effect of patient, tumor, and other predictive factors. The median age was 60 years (range: 20-90), the majority were male (n = 105; 56%) and white (n = 167; 89%). Stages of disease were 1A (n = 87; 46%), 1B (n = 5; 3%), 2A (n = 73; 39%), and 2B (n = 23; 12%). Seventy-five (40%) patients had germinal center B-cell subtype. 27 (14%) were identified as DHL (7 typical and 20 atypical), and 10 (5%) were identified as THL (3 typical and 7 atypical). In those treated with chemotherapy (CT) alone, the median number of CT cycles was 6 (range: 1-10), and in patients treated with CT and RT it was 4 (range: 0-8, P<0.001). Median follow-up from treatment completion was 33 months (0.3-204 months). Median RT dose was 36 Gy (20-54 Gy). A total of 40 patients (21%) were known to be dead at last analysis. The receipt of RT was significant on MVA for the TTR with a HR 0.38 (0.20 -0.71; P = 0.002) with a trend for OS on MVA (P = 0.08). TTR at 36 months was 46% and 83% in patients treated without and with RT (P<0.0001). MVA demonstrated significance for OS in THL vs. DHL with a HR 6.1 (1.6-22.8, P = 0.01), and THL vs. none with a HR 4.5 (1.4-12.9, P = 0.02). MVA demonstrated significance for TTR in THL vs. none HR 6.6 (1.4-30.7, P = 0.05). TTR and OS rates at 36 months were 80%/83%, 47%/72%, and 17%/44% in patients without analyzed genetic aberrations, DHL, and THL (P < 0.0001 and P = 0.0002), respectively. DHL and THL patients treated with R-CHOP benefited significantly from consolidative RT with a 36 month TTR rate of 64% and 11% in patients treated with and without RT, respectively (P = 0.04). The receipt of RT and DHL/THL status were the only factors that correlated with TTR on MVA. DHL and THL status correlated with worse OS, and consolidative RT may offer a significant benefit to this cohort of patients. Early identification of these patients for more aggressive treatment utilization may lead to improved outcomes.

Gemcitabine and cisplatin in inoperable, loco-regionally advanced and metastatic gallbladder cancer: A study from Northern India cancer institute

Aims: The primary objective of this study was to determine the response rates of the gemcitabine and cisplatin combination chemotherapy in treatment naive patients with inoperable gall bladder cancer. The secondary objectives were to evaluate the toxicity, progression free survival (PFS), and overall survival. Materials and Methods: Treatment naive patients with histologically proven inoperable gallbladder cancer treated with gemcitabine and cisplatin chemotherapy between March 2010 and December 2014 were included in this retrospective study. The dose of gemcitabine and cisplatin was 1 g/m2 on day 1 and 8, and 75 mg/m2 on day 1, in a 21-day cycle respectively. Computed tomography scan was used for response assessment. Results: There were 32 men and 59 women with a median age of 52 years (range 30–67 years). Of the 91 patients, 9 (9.9%) patients achieved a complete response and 41 (45.1%) patients achieved a partial response for an overall response rate of 55%. The median number of chemotherapy cycles administered were 6 (range 1–9). The median progression free survival (PFS) was 5.4 months [95% confidence interval (CI) 3.9–7.9 months], with one year survival rate of 34.1%. Common toxicity criteria grade 3 or 4 anemia was seen in 4 (4.4%) and 2 (2.2%) patients respectively. Grade 3 neutropenia and thrombocytopenia was observed in 10 (10.9%) and 9 (9.9%) patients respectively. Conclusion: The combination of gemcitabine and cisplatin is active in advanced gallbladder carcinoma with mild toxicity.

Intensity-modulated radiation therapy followed by GDP chemotherapy for newly diagnosed stage I/II extranodal natural killer/T cell lymphoma, nasal type.

Extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTL) is an aggressive non-Hodgkin lymphoma and the majority of ENKTL cases are diagnosed at the localized stage. Radiotherapy in combination with chemotherapy has been used for localized ENKTL, but the optimal combination treatment modality and the best first-line chemotherapy regimen have not been defined. In this retrospective study, 44 patients with newly diagnosed, stages I/II ENKTL were enrolled and received intensity-modulated radiation therapy (IMRT, 50-56Gy) followed by GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy. The median number of chemotherapy cycles per patient was 4 (range, 2-6 cycles). At the end of treatment, the overall response rate was 95% (42/44), including 39 patients (89%) who attained complete response. Two patients developed systemic progression after IMRT. With a median follow-up of 37.5months, the 3-year overall survival (OS) rate and progression-free survival (PFS) rate were 85% (95% CI, 74 to 96%) and 77% (95% CI, 64 to 91%), respectively. Locoregional and systemic failure rates for this treatment were 9% (4/44) and 14% (6/44), respectively. The most common grades 3 to 4 adverse events included leukopenia (37%), neutropenia (34%), and mucositis (25%). No treatment-related deaths were observed. This study suggested high efficacy and low toxicity of IMRT followed by GDP regimen chemotherapy for newly diagnosed stage I/II ENKTL patients. These results require further investigation in prospective trials.

Dose dense MVAC prior to radical cystectomy: a real-world experience.

Our primary endpoint was to assess pathological response rate (pT0N0 and ≤pT1N0) for patients with BCa treated with the accelerated or dose dense MVAC (ddMVAC) chemotherapy followed by radical cystectomy (RC) in this real-word multi-institutional cohort. We retrospectively reviewed records of patients with urothelial cancer who underwent ddMVAC and RC at seven contributing institutions from 2000 to 2015. Patients with cT2-4a, M0 BCa were included. Presence of cT3-4 disease, hydronephrosis, lymphovascular invasion and/or existence of sarcomatoid, or micropapillary features on the initial transurethral resection of bladder tumor specimen was defined as high-risk disease. Logistic regression models for prediction of pT0N0 and ≤pT1N0 were generated for the entire cohort as well as for the cN0 subgroup. The multivariable Cox proportional hazards regression model for survival using post RC data was used to assess hazard ratios (HRs) for the variables of interest. A total of 345 patients received ddMVAC chemotherapy during the study period; 85% had high-risk features. The median number of chemotherapy cycles was 4 (IQR 4-4); >90% of patients completed all scheduled cycles. The observed rates of pT0N0 and ≤pT1N0 were 30.4 and 49.3%, respectively, among cN0 patients. On the multivariable regression model, the presence of more than one clinical high-risk element was associated with 70% [OR 0.30 95% CI (0.10-0.86); p=0.02] reduction in the odds of achieving partial pathological response. A complete response (pT0N0) was observed in one-third of patients after neoadjuvant ddMVAC therapy, and a partial response (≤pT1N0) was observed in nearly half of the cases in this real-world experience with this regimen. To our knowledge, this represents the largest experience outside clinical trial settings.

Multicenter Retrospective Analysis of Clinical Characteristics, Treatment Patterns, and Outcomes in Very Elderly Patients with Diffuse Large B-Cell Lymphoma: The Korean Cancer Study Group LY16-01.

PurposeThe treatment strategy for elderly patients older than 80 years with diffuse large B-cell lymphoma (DLBCL) has not been established because of poor treatment tolerability and lack of data.Materials and MethodsThis multicenter retrospective study was conducted to investigate clinical characteristics, treatment patterns and outcomes of patients older than 80 years who were diagnosed with DLBCL at 19 institutions in Korea between 2005 and 2016.ResultsA total of 194 patients were identified (median age, 83.3 years). Of these, 114 patients had an age-adjusted International Prognostic Index (aaIPI) score of 2-3 and 48 had a Charlson index score of 4 or more. R-CHOP was given in 124 cases, R-CVP in 13 cases, other chemotherapy in 17 cases, radiation alone in nine cases, and surgery alone in two cases. Twenty-nine patients did not undergo any treatment. The median number of chemotherapy cycles was three. Only 37 patients completed the planned treatment cycles. The overall response rate from 105 evaluable patientswas 90.5% (complete response, 41.9%). Twentynine patients died due to treatment-related toxicities (TRT). Thirteen patients died due to TRT after the first cycle. Median overall survival was 14.0 months. The main causes of death were disease progression (30.8%) and TRT (27.1%). In multivariate analysis, overall survival was affected by aaIPI, hypoalbuminemia, elevated creatinine, and treatment.ConclusionAge itself should not be a contraindication to treatment. However, since elderly patients show higher rates of TRT due to infection, careful monitoring and dose modification of chemotherapeutic agents is needed.

Abstract NTOC-096: INTRAPERITONEAL CHEMOTHERAPY AFTER PRIMARY OR INTERVAL DEBULKING SURGERY FOR ADVANCED EPITHELIAL OVARIAN CANCER

Abstract PURPOSE: To evaluate the outcomes of intraperitoneal (IP) chemotherapy compared with those of intravenous (IV) chemotherapy in patients with advanced ovarian cancer treated either with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) or with primary debulking surgery (PDS). METHODS: Patients diagnosed with FIGO stage III or IV epithelial ovarian, fallopian tube or primary peritoneal carcinoma treated at our institutions with PDS or NACT and IDS from 2006-2014 were identified. Covariates were compared using chi-square analyses, t-tests and Mann-Whitney tests. Survival rates were calculated using the Kaplan-Meier method and compared with log rank tests and Cox multivariate regression models. RESULTS: Sixty one patients received NACT and underwent IDS with residual disease of ≤ 1 cm; 40 patients (65.6%) received IP chemotherapy and 21 patients (34.4%) were given IV chemotherapy after IDS. The median number of chemotherapy cycles was three (range 3-8), and 34 patients (85.0%) completed the prescribed dose of IP chemotherapy. The median progression free survival was 16.5 months in the IP group and 15.0 months in the IV group (p = 0.88). The estimated median overall survival was 64.0 months in the IP group and 42.0 months in the IV group (p = 0.12). During the same study period, 148 patients underwent optimal PDS after which 93 patients (83.6%) received IP chemotherapy and 55 patients (37.2%) were given IV chemotherapy. Patients after IP chemotherapy had improved survival outcomes when compared to patients after IV chemotherapy. The median progression free survival was 29.0 months after IP chemotherapy and 16.0 months after IV chemotherapy (p &amp;lt; 0.0001) and the median overall survival was 93.0 months after IP chemotherapy and 43.0 months after IV chemotherapy (p &amp;lt; 0.0001). CONCLUSIONS: Although IP chemotherapy after PDS showed improved survival, IP chemotherapy after NACT and IDS, while tolerable with high rates of completion, did not demonstrate a survival advantage over IV chemotherapy in our patients. Citation Format: Jessica Lee MD, John P Curtin MD, Franco M Muggia MD, Bhavana Pothuri MD, Leslie R. Boyd MD, Jing-Yi Chern MD, Melissa K Frey MD, Stephanie V Blank MD. INTRAPERITONEAL CHEMOTHERAPY AFTER PRIMARY OR INTERVAL DEBULKING SURGERY FOR ADVANCED EPITHELIAL OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr NTOC-096.

Phase I/II study of induction chemotherapy using carboplatin plus irinotecan and sequential thoracic radiotherapy (TRT) for elderly patients with limited-disease small-cell lung cancer (LD-SCLC): TORG 0604

BackgroundThe role of irinotecan for elderly patients with LD-SCLC has been unclear, and the timing of TRT combined with chemotherapy has not been fully evaluated.MethodsPatients aged > 70 years with untreated, measurable, LD-SCLC, performance status (PS) 0–2, and adequate organ function were eligible. Treatment consisted of induction with carboplatin on day 1 and irinotecan on days 1 and 8, every 21 days for 4 cycles, and sequential TRT (54Gy in 27 fractions). Carboplatin doses were based on AUC of 4 and 5 (levels 1 and 2, respectively), with a fixed irinotecan dose (50 mg/m2). Primary objective of the phase II study was overall responce rate. ResultsForty-three patients were enrolled and forty-one were finally analyzed (median age: 75 years [range 70–86 years); males 31; PS 0/1/2, n = 22/18/1]. Two patients were excluded because of protocol violation (ascertained to be extensive disease). Twelve patients were accrued at phase I and the number of patients with carboplatin dose-limiting toxicities at levels-1 (n = 6) and −2 (n = 6) were 1(grade 3 hypertension) and 2 (grade 4 thrombocytopenia), respectively. The phase II trial was expanded to 29 additional patients receiving the level 1 carboplatin dose, total of 35 patients. The median number of chemotherapy cycles was 4 (range 1–4), and the median radiation dose was 54Gy (range 36–60). Toxicities were generally mild. There were 4 complete and 27 partial responses (response rate 88.6%). With a median follow-up of 52 months, the median progression-free and overall survival times of phase II were 11.2 and 27.1 months, respectively.ConclusionsInduction chemotherapy of carboplatin plus irinotecan and sequential TRT was well tolerated and effective for elderly patients with LD-SCLC. Additional confirmatory studies are warranted.Trial registrationTrial registration number: UMIN000007352Name of registry: UMIN.Date of registration: 1/Dec/2006.Date of enrolment of the first participant to the trial: 6/Feb/2007.Clinical trial registration date: 1/Feb/2006 (prospective).

Additional chemotherapy and salvage surgery for poor response to chemoradiotherapy in rectal cancers.

A proportion of locally advanced rectal cancer patients who receive neoadjuvant chemoradiotherapy (NACRT) are still unresectable. This study was undertaken to assess the outcomes of giving additional chemotherapy to rectal cancer patients with unresectable disease after NACRT. Patients with poor response to NACRT where mesorectal fascia was still involved on MRI and R0 resection was doubtful, received additional four cycles of chemotherapy with either CAPOX or FOLFIRINOX regimen, and the response was reevaluated with MRI and reassessed for surgical resection. Between June 2012 and December 2014, 50 patients received additional chemotherapy with CAPOX regime (19%, 38%) or FOLFIRINOX (31%, 62%) after CRT. Median number of chemotherapy cycles received was four (range 2-8 cycles). Overall 34 (68%) patients underwent exploration and 31 (62%) underwent R0 resection. The median time to surgery following chemoradiation was 5 months (range 3-18 months). Complete pathological response was seen in seven (22%) patients. Patients with poor response to NACRT may be further downstaged using additional chemotherapy so as to achieve R0 resection in 62% of cases.

Brachytherapy Combined With Surgery for Conservative Treatment of Children With Bladder Neck and/or Prostate Rhabdomyosarcoma

To report the results of a conservative strategy based on partial surgery combined with brachytherapy in a prospective cohort of children with bladder-prostate rhabdomyosarcoma (BP RMS). We prospectively documented the outcome of children treated in our department between 1991 and 2015 for BP RMS and undergoing a multimodal approach combining conservative surgery (partial cystectomy and/or partial prostatectomy) and perioperative interstitial low-dose-rate or pulse-dose-rate brachytherapy. Before brachytherapy, children had received chemotherapy with modalities depending on their risk group of treatment. A total of 100 patients were identified, with a median age of 28months (range, 5.6 months-14 years). According to the Intergroup Rhabdomyosarcoma Study (IRS) group, 84 were IRS-III, and 12 were IRS-IV tumors. Four patients were treated at relapse. The median number of chemotherapy cycles before local therapy was 6 (range, 4-13). After surgery, 63 patients had a macroscopic tumor residuum. Five patients underwent a brachytherapy boost before pelvic external beam radiation therapy because of nodal involvement, and 95 had exclusive brachytherapy. Median follow-up was 64months (range, 6 months-24.5years). Five-year disease-free and overall survival rates were 84% (95% confidence interval 80%-88%) and 91% (95% confidence interval 87%-95%), respectively. At last follow-up most survivors presented with only mild to moderate genitourinary sequelae and a normal diurnal urinary continence. Five patients required a secondary total cystectomy: 3 for a nonfunctional bladder and 2 for relapse. Brachytherapy is effective as part of a conservative strategy for BP RMS, with a relatively low delayed toxicity as compared with previously published studies using external beam radiation therapy. Longer follow-up is required to ensure that the functional results are maintained over time.

The impact of peri-operative chemotherapy for patients with lymph node-positive urothelial cancer.

388 Background: Patients with locally advanced urothelial cancer with regional lymph node involvement (LN+) have a poor prognosis. Surgical management of these patients is controversial and practice patterns vary. We evaluated the outcomes of patients with LN+ disease treated with pre-operative chemotherapy and cystectomy, cystectomy and post-operative chemotherapy, and chemotherapy alone. Methods: Patients with urothelial cancer with TxN1-3M0 disease treated with chemotherapy in Alberta from 2005 to 2015 were evaluated. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier analysis. Cox regression analysis was performed to evaluate the impact of age, gender, T stage, and N stage on survival. Results: 184 patients with LN+ disease treated with chemotherapy were evaluable for outcomes; 42 underwent pre-operative chemotherapy (Group A), 92 underwent post-operative chemotherapy (Group B), and 50 received chemotherapy alone (Group C). The median age at diagnosis was 65 years (range 31-89) and most patients (83%) were male. The median follow-up time was 23.2 months. A higher T stage was seen in patients in Group A, while patients in Group C had a higher N stage. The median number of chemotherapy cycles delivered was equal in all arms at 4. Patients in Group A or B had significantly better PFS and OS compared with patients in Group C (Table). When adjusting for age, gender, T stage, and N stage, patients in Group C had significantly lower OS compared with those patients in Group A (HR 1.87, 95% CI 1.09 – 3.18, p=0.02). Conclusions: In this real-world analysis of patients with LN+ urothelial cancer, patient outcomes were improved with surgical resection of disease in combination with pre-operative chemotherapy. After chemotherapy in fit patients with LN+ disease, surgical management is a reasonable consideration. [Table: see text]

Carboplatin-based concurrent chemoradiation therapy in locally advanced head and neck cancer patients who are unfit for cisplatin therapy.

Cisplatin-based chemoradiation (CTRT) is the standard of care in locally advanced head and neck cancers. Limited treatment options are available in patients unfit for cisplatin. This audit was carried out to study the toxicities, tolerance, and outcomes of carboplatin-based CTRT in patients who are not eligible for cisplatin. A total of 63 locally advanced head and neck cancer patients treated between January 2011 and October 2015 were administered carboplatin-based CTRT. The dose of carboplatin was equivalent to area under the curve equivalent to 2 administered once a week for a maximum of 7 cycles. Toxicity was coded as per the CTCAE version 4.03. SPSS software version 16 was used for statistical analysis. Descriptive statistics was performed. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier survival analysis. Cox proportional hazard model was used for identifying factors affecting PFS and OS. The reasons for patients being unfit for cisplatin were low serum creatinine clearance in 41 (65.07%), sensorineural hearing loss in 18 (28.57%), uncontrolled medical comorbidities in 3 (4.76%), and old age in 1 patient (1.6%). 53 patients (84.1%) completed planned radiotherapy. The median number of chemotherapy cycles administered was 6. Grade 3-4 toxicities were seen in 32 patients (50.8%). The median OS and PFS were 28 months (95% confidence interval [CI]: 20.9-34.6 months) and 17 months (95% CI: 08.2-25.7 months), respectively. Age was the only factor significantly affecting OS and PFS. Carboplatin-based CTRT is well tolerated in patients unfit for cisplatin and seems to have superior outcomes than those reported in radical radiotherapy studies.

OA04.02 Smoking Behavior in Patients with Early Stage Non-Small Cell Lung Cancer: A Report from ECOG-ACRIN 1505 Trial

Approximately 85% of lung cancer is related to cigarette smoking. Smoking cessation has been reported to benefit patients even after the diagnosis of lung cancer. We studied the smoking behavior of patients with lung cancer in a phase 3 study for early stage lung cancer. The ECOG-ACRIN 1505 study enrolled patients with stages IB, II and IIIA non-small cell lung cancer (NSCLC) after they had undergone surgical resection. It was designed to evaluate whether the addition of bevacizumab would improve survival relative to cisplatin-based chemotherapy alone. Studying the correlation between smoking status and outcome was a secondary endpoint. Patients completed a questionnaire about their smoking habits at baseline, 3, 6, 9 and 12 months after study entry. Out of 1501 patients enrolled, 99%, 90%, 85%, 82% and 80% responded to the questionnaire at baseline, 3, 6, 9 and 12 months respectively. Nearly 90% reported having smoking during their lifetime. At study entry, 12% reported ongoing smoking. The median age patients started smoking was 17 years and the median age at which they quit smoking was 55 years. The median number of cigarettes smoked per day was 20. Approximately 4% smoked cigars (median number 2/day). Of the 40% that reported smoking after the diagnosis of lung cancer, only 15% reported smoking at 12 months. At 12 months after study entry, among those who continued to smoke, 79% reported smoking fewer cigarettes/day, whereas 11% smoked more cigarettes. When asked about the number of cigarettes smoked at 12 mos, 63% reported smoking fewer than 10 cigarettes/day. The incidence of grades 3-5 toxicity was 76% in smokers versus 69% in non-smokers (p=0.06). There were no differences in dose reductions for chemotherapy (P=0.55) or bevacizumab (P=0.90) between smokers and non-smokers. The median number of chemotherapy cycles were nearly identical for smokers and never-smokers. The disease-free survival (DFS) and OS for smokers relative to never-smokers were 0.97 (P=0.83) and 1.54 (P=0.01) respectively. This is the first comprehensive, prospective report of smoking habits of patients with lung cancer. There were a high rate of smoking cessation and reduction in number of cigarettes smoked, that was maintained at 12m after study entry. Toxicity and DFS did not differ significantly between smokers and never-smokers, though overall survival was more favorable with the never-smokers. Study was coordinated by ECOG-ACRIN (Robert L. Comis, M.D., Chair) and supported in part by Public Health Service Grants CA180820, CA180888, CA180821, & CA180863.

Benefit of Consolidative Radiotherapy in Patients with Limited Stage Diffuse Large B-Cell Lymphoma in the Rituximab Era

Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma and the most common lymphoid neoplasm in adults. In the pre rituximab era, the standard therapy for patients with limited stage DLBCL had been three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) followed by involved-field radiotherapy (IFRT). The addition of rituximab has revolutionized the treatment of DLBCL. Rituximab combined with CHOP (R-CHOP) has been established as the standard treatment for patients with DLBCL. However, the role of consolidative radiotherapy (RT) in the treatment of limited stage DLBCL in the rituximab era is controversial.Patients and Methods: We retrospectively analyzed 108 patients with limited stage DLBCL who received R-CHOP or R-THP-COP (rituximab plus, cyclophosphamide, pirarubicin, vincristine and prednisone) regimen between June 2004 and August 2015. We compared overall survival (OS) and progression-free survival (PFS) according to the treatment. OS was calculated from the date of initiation of chemotherapy to the date of the last follow-up or death. PFS was calculated from the date of initiation of chemotherapy to the date of progression disease, death, or last contact, whichever occurred first. Survival was estimated from Kaplan-Meier curves and compared using the log-rank test. P < 0.05 was considered statistically significant. Weighted Cox proportional hazards regression modeling with the inverse probability weighted (IPW) estimators method adjusting to propensity for RT was used to account for differences in baseline characteristics.Results: Median age at diagnosis was 66 years (19-88 years), with 61 males and 47 females. Forty-three patients (40%) had stage I, and 65 patients (60%) received consolidative RT after chemotherapy. Patients who received consolidative RT were significantly younger (65 vs 72, P < 0.01) and were more likely to have stage I disease (51% vs 23%, P < 0.01). The median number of chemotherapy cycles was 4 (range 3-8) in patients who received RT, and 6 (range 3-8) in patients who did not. Median follow-up was 4.3 years (0.3-10.9 years), and the 5-year OS (92% vs 63%, P < 0.01) and PFS (87% vs 65%, P < 0.01) were significantly higher for patients who received RT than those who did not. Using IPW adjustment, RT remained predictive of OS (HR 0.30, CI 0.13-0.72, P < 0.01) and PFS (HR 0.47, CI 0.22-0.99, P < 0.05).Conclusion: Our results suggest that consolidative RT improves OS and PFS in patients with limited stage DLBCL in the rituximab era. Although consolidative RT seems to be gradually phased out by chemotherapy alone, it is still an important treatment strategy. DisclosuresNo relevant conflicts of interest to declare.

Pretreatment tumor volume as a prognostic factor in metastatic colorectal cancer treated with selective internal radiation to the liver using yttrium-90 resin microspheres.

Yttrium-90 (90Y)-resin microspheres can prolong intrahepatic disease control and improve overall survival (OS) in patients with metastatic colorectal cancer (CRC). Prognostic factors for improved outcomes in patients undergoing selective internal radiation therapy (SIRT) have been studied, but the relationship between pre-SIRT liver tumor volume and outcomes has not well described. We retrospectively reviewed the records of patients with metastatic CRC who were treated at our institution with 90Y-resin microspheres. Each patient underwent either MR or CT imaging of the liver with intravenous (IV) contrast before and within ~2-3 months after SIRT. Imaging data were transferred into our treatment planning system. Each metastatic liver lesion was contoured, and the volume of each lesion was summed to determine the total liver tumor volume at a given time point. We evaluated whether pretreatment liver tumor volume was related to OS. We also evaluated the relationship between pre-SIRT tumor volume and radiographic treatment response by either unidimensional Response Evaluation Criteria in Solid Tumors (RECIST) or three-dimensional volumetric criteria. We included 60 patients with a median age of 59 years (range, 38-97 years); 60% of patients received sequential lobar treatment. The median number of chemotherapy cycles received prior to SIRT was 2. Median follow-up from first SIRT was 8.9 months. Pre- and post-SIRT tumor volumes were primarily calculated on CT (87%). The median pre-SIRT tumor volume was 77 cc (range, 4.5-2,170.4 cc). The median intervals between the first SIRT and the first, second, and third follow-up scans were 2.2, 4.4, and 7.7 months, respectively. No patient experienced a radiographic complete response. Pretreatment volume was a significant predictor for estimating the odds of a patient having stable disease or partial response using volumetric response criteria at first (P=0.016), second (P=0.023), and third (P=0.015) follow-ups. For each unit increase in log volume, a patient's odds of having a stable or partial response were 0.57, 0.63, and 0.61 times as likely at first, second, and third follow-up, respectively. OS was not significantly associated with pretreatment tumor volume. Patients with metastatic CRC with larger overall pretreatment liver tumor volumes, regardless of number of individual liver lesions, are less likely to have radiographic evidence of stable disease or partial response following SIRT using volumetric response criteria. However, pretreatment volume was not significantly associated with OS, and thus SIRT should be considered for patients with larger pretreatment volumetric tumor burden.

319P Choriocarcinoma: A 10 year tertiary care cancer hospital experience

Background Gestationalchorio-carcinomasarehighlymalignanttumorsof trophoblastic tissue occuring during or after pregnancy. Very little data is available in Pakistan. Methods Patients diagnosed as choriocarcinoma managed at Shaukat Khanum Cancer hospital, Lahore, Pakistan from 2005 to 2015 were included. Data was recorded on age, risk scoring, pre and post-operative B-human chorionic gonadotropins (B-hCG) levels, treatment, type and number of chemotherapy cycles, type of surgery and overall survival(OS).OSbyKaplanMeiermethodwastheintervalbetweenthedateof diagnosis and last visit/death. Results Thirty eight patients with choriocarcinoma with median age of 25 years were included. Using FIGO staging, stage 1 was identified in 7, II in 1, III in 14, IV in 8 and unknown in 8 patients respectively. Pre-treatment Beta-hCG ranged from 28 to 921000 ug/l. Twenty-seven patients (71.0%) had high risk category, 7 (18.4%) in medium risk and 4 (10.5%) had low risk. EMA-CO was the most common initial regimen (35 patients). Four patients, as non-responders to EMA-CO, were later on treated by EP-EMA protocol. Median number of chemotherapy cycles was 6.Mean time to normalization ofBeta-hCGwas 7.26 + 2.24 weeks. Thirtythree patients completedallchemotherapycycles.PosttreatmentBeta-hCGlevelsnormalizedinall patientsexceptfournonresponderstoEMA-CO;howeverdiseasewasnotcontrolled in these patients. Thirty three patients achieved complete response. Five patients expired, while 3 were lost to followup after treatment. Thirtyoutof38 patients werealiveatmedianfollowupof52months.MediansurvivalbyKaplanMeier method was yet not reached. Conclusions Choriocarcinoma is a curable malignancy and chemotherapy can achieve high cure rates and inadvertent surgery should be avoided in all cases unless deemed necessary. Legal entity responsible for the study Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Funding Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Disclosure All authors have declared no conflicts ofinterest.

A prospective, multicenter, phase II clinical study of concurrent chemotherapy and thoracic three-dimensional radiotherapy for stage IV non-small cell lung cancer -Impact of clinical factors on survival (PPRA-RTOG003)

Objective To investigate the impact of clinical factors on survival in patients receiving concurrent chemotherapy and three-dimensional radiotherapy (3DRT) for stage IV non-small cell lung cancer (NSCLC). Methods A total of 203 patients were enrolled in a prospective clincial study from 2008 to 2012, and among these patients, 178 patients were eligible for analysis of clinical factors. All patients were treated with platinum-based doublets chemotherapy, with a median number of chemotherapy cycles of 4(2-6 cycles) and a median dose of 3DRT of 60.3 Gy (36.0-76.5 Gy). The Kaplan-Meier method was used to calculate overall survival (OS) rates, the log-rank test was used to compare survival rates between groups, and the Cox regression model were used for multivariate analysis. Results The 1-, 2-, and 3-year overall survival rates were 56%, 16%, and 10%, respectively, and the median survival time was 13 months (95% CI=11.500-14.500). The univariate analysis showed that platelet count ≤221×109/L, neutrophil count ≤5.2×109/L, white blood cell count<7×109/L, and improvement in Karnofsky Performance Scale (KPS) after treatment significantly prolonged OS (P=0.000, 0.022, 0.003, and 0.029), and metastasis to a single organ and hemoglobin≥120 g/L tended to prolong OS (P=0.058 and 0.075). The multivariate analysis showed that white blood cell count<7×109/L, platelet count ≤221×109/L, and improvement in KPS after treatment were beneficial to OS (all P<0.05). Conclusions White blood cell count and platelet count before treatment and KPS after treatment are prognostic factors for patients with stage IV NSCLC receiving concurrent chemotherapy and 3DRT. Clinical Trial Registry ClinicalTrials.gov, registration number: ChiCTRTNC10001026. Key words: Carcinoma, non-small cell lung/three-dimensional radiotherapy; Carcinoma, non-small cell lung/concurrent chemoradiotherapy; Clinical factors; Prognosis

Postoperative radiotherapy combined with concurrent paclitaxel-nedaplatin chemotherapy for esophageal cancer: a preliminary study

Objective To investigate the safety and preliminary effect of postoperative intensity-modulated radiotherapy (IMRT) combined with concurrent weekly paclitaxel-nedaplatin chemotherapy for patients with esophageal squamous cell carcinoma. Methods A total of 52 patients who were treated from 2010 to 2013 were enrolled. The clinical target volume of IMRT included tumor beds and corresponding lymphatic drainage regions at high risk, and the total radiotherapy dose was 50-60 Gy, 2.0 Gy/fraction, 5 fractions per week. The concurrent chemotherapy consisted of nedaplatin 25 mg/m2 on D1 and paclitaxel 45-50 mg/m2 on D1 and was repeated every week during radiotherapy. Common Terminology Criteria for Adverse Events 4.0 was used to evaluate adverse events, and the Kaplan-Meier method was used for survival analysis. Results All the patients had good tolerance to the treatment, and 51 patients (98%) completed radiotherapy according to the scheduled regimen. The median number of chemotherapy cycles was 4, and 42 patients (81%) completed ≥3 cycles of chemotherapy. Most adverse events were of grade 1-2, and grade 3 adverse events were leucopenia (29%), radiation esophagitis (10%), and anastomotic stenosis (4%). One patient (2%) experienced grade 5 gastroesophageal bleeding. Of all the patients, the median survival time was 38.7 months, and the 1-, 2-, 3-, and 4-year overall survival rates were 83%, 64%, 51%, and 38%, respectively. The overall recurrence rate was 46.2%, and the locoregional recurrence rate and distant metastasis rate were 15% and 37%, respectively. Conclusions Postoperative IMRT combined with concurrent weekly paclitaxel-nedaplatin chemotherapy for patients with esophageal squamous cell carcinoma is safe and effective, and large-scale prospective randomized studies are needed. Key words: Esophageal neoplasms/radiochemotherapy; Radiochemotherapy, concurrent; Efficacy; Security

Feasibility and impact on resectability of FOLFIRINOX in locally-advanced and borderline pancreatic cancer.

318 Background: Pancreatic cancer (PC) has a poor prognostic. Only patients who undergo a complete R0 surgery have longer survival rates. Treatment of locally-advanced (LA) and borderline (BL) PC is controversial. Folfirinox is considered as a standard first-line treatment in metastatic patients. The aim of our study was to evaluate the impact of Folfirinox in LA and BL PC. Methods: We performed a retrospective analysis of prospectively-collected data from LA and BL PC patients treated with original Folfirinox in our institution between January 2010 and February 2015. Results: 35 patients were enrolled, 20(57.1%) pancreatic head adenocarcinoma, 19(54.3%) LA and 16(45.7%) BL PC, 54.3% male, median age 60 years old [44-74]. OMS was 0, 1, 2 for 21(61.8%), 11(32.4%), 2(5.9%) patients. Median CA19.9 level was 5N [1-33]. All patients had Folfirinox in first-line followed by radiochemotherapy (RTCT) in 23(65.7%) patients, with Gemzar and Xeloda in 21 and 2 patients. Median number of chemotherapy cycles was 4 [1-13]. The grade 3-4 toxicity rate was 17.1% (n = 6), mainly digestive (67%), hematologic (16.7%), none neurologic. There was no toxic death. 17(46%) patients underwent surgery, 7 LA and 10 BL, with a R0 resection in 13 patients, mainly 8 PT3 (57.1%), no PT0, and 14N+. The morbidity rate was 40%, including 3 fistulae and 2 hemorrhages. Median overall survival was 24 months (95%CI:14-44), 53 (95%CI:26-.) and 12 months (95%CI: 9-19) in surgery versus no-surgery patients (p&lt; 0.001). Progression-free survival was 13.9 months (95%CI:11.2-17.1), 16.2 (95%CI:13.7-25.3) and 9.5 (95%CI:7.4-15.9) months in surgery versus no-surgery patients. 13 patients were still alive at the time of analysis, with a median follow-up of 44 months (95%CI:7-53). 30 patients had disease progression, locally, distant or both in 7(24.1%), 20(69.0%) and 3(13.1%) patients. Weight loss, OMS status, abdominal pain and CA199 level at diagnosis were not correlated with better survival. Conclusions: Folfirinox, followed or not by RTCT, as inductive treatment for LA and BL PC is feasible with acceptable toxicity, and allowed resectability in 37.1% patients, and thus a longer survival. Further studies are needed to confirm these encouraging results.