Postoperative Chemo Research Articles

Unradical Surgery for Locally-Advanced Thymoma: Is it time to evolve Perspectives?

ObjectivesNearly-one-third of thymomas are locally-advanced at diagnosis. The traditional dogma that surgery is justified in case a complete resection can be achieved has remained unmovable until today. This study aimed to investigate feasibility and oncologic efficacy of incomplete resection for locally-advanced thymomas in a contest of multimodality therapy. Materials and MethodsA retrospective analysis was conducted using data of prospectively maintained thymomas database in a single high-volume centre. Data on 285 consecutive patients undergoing surgery for stage III and IVa thymomas between 1995 and 2019 were reviewed. Patients who underwent incomplete resection with curative-intent (removal of at least 90% of tumour burden) were included. Long-term outcomes and predictors of cancer-specific survival (CSS) and progression-free survival (PFS) were analyzed. Secondary endpoint was to assess adjuvant therapy efficacy. ResultsThe study included 79 patients, 60 with microscopic residual tumour (76%, R1) and 19 with macroscopic residual disease (24%, R2). Masaoka-Koga stage was: III in 41 patients (52%) and IVa in 38 (48%). Histology was B2-thymomas (n = 31, 39.2%) followed by B3 (n = 27, 34.2%). Five- and 10-years CSS was 88% and 80%. Seventy patients (90%) underwent adjuvant treatment; they showed CSS comparable to radical resected patients (5-years: 89.1% vs 98.9%, respectively; 10-years: 81.8% vs 92.7%, respectively, p = 0.43). The site of residual disease, Masaoka-Koga stage and WHO histology did not affect prognosis. Stepwise multivariable analysis confirmed adjuvant therapy as a favourable CSS prognostic factor (HR, 0.51; 95% CI, 0.33–0.79, p = 0.003). Stratifying by subgroups, R2-patients who received postoperative chemo(radio)therapy (pCRT) showed a significantly better prognosis than R2-patients treated by consolidation radiotherapy alone (10-years CSS: 60%, p < 0.001). ConclusionIn locally-advanced thymomas, whenever a radical surgery cannot be achieved, incomplete resection has proved to be effective in a contest of multimodality strategy, independently of WHO histology, Masaoka-Koga stage and site of residual disease.

The Systemic Immune-Inflammation Index (SII) Increases the Prognostic Significance of Lymphovascular Invasion in Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy.

Lymphovascular invasion (LVI) and systemic immune-inflammation index (SII) both have been proved to correlate with oncologic outcomes in upper tract urothelial carcinoma (UTUC). We hypothesize that integrating SII with LVI may be an aid for risk-stratification of prognosis. This study aimed to evaluate the prognostic significance of combined SII and LVI in patients with localized UTUC. A retrospective analysis of clinicopathological data of 554 UTUC patients who underwent radical nephroureterectomy (RNU) was conducted. The SII was calculated using the equation (preoperative serum neutrophil*platelet/lymphocyte). Use of Kaplan-Meier analyses and Cox proportional hazards models were to evaluate associations of combining SII and LVI with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Furthermore, receiver operating characteristic (ROC) analysis was applied to estimate predictive ability of combining SII and LVI for oncological outcomes. Positive LVI was significantly associated with advanced stage, high grade, necrosis, lymph node metastasis, and high-level SII. Positive LVI and high-level SII co-existence was significantly associated with unfavorable OS, CSS, and PFS in Kaplan-Meier analyses (all p < 0.001) and was an independent indicator of OS, CSS, and PFS (HR [95% CI]: 3.918 [2.168-7.078], 5.623 [2.679-11.801], 3.377 [2.138-5.334]), respectively) in multivariate analyses. Furthermore, adding LVI and SII to a model that included standard pathologic predictors exhibited a better ability to predict survival in ROC analysis. The integration of SII and LVI was demonstrated to be a potential factor of poor outcomes in patients with localized UTUC. Notably, the combined use of LVI and SII can be a feasible and complementary factor to TNM staging in the prognostic assessment of UTUC patients in clinical practice. The validity of combination of the two markers would be considered in future prospective studies to evaluate its usefulness in staging and application of post-operative chemo or immunotherapy.

Abstract 6299: Population kinetics (PopKin) of non-small cell lung cancer (NSCLC) adjuvant therapy

Abstract Background: Disease-free survival (DFS) and overall survival (OS) follow 1st order kinetics. Curve Popkin assessment yields biological insights. Chemotherapy (chemo) improves outcome in resected NSCLC. We performed adjuvant DFS and OS PopKin assessments. Methods: We digitized published DFS and OS curves. We used GraphPad Prism for curve exponential decay nonlinear regression analysis (EDNLRA). Results: We assessed 1 trial with adjuvant osimertinib and 5 with platinum-based postoperative chemo and control arms. With osimertinib, DFS and OS curves were convex on log-linear plots, suggesting rapid tumor regrowth once therapy is discontinued. In chemo trials, 10 of 10 DFS curves and 9 of 10 OS curves fit 2-phase decay EDNLRA models (Table 1). Popkin calculations indicate that of control patients destined to recur, 12% would recur by 2 months after surgery, 22% by 4 months and 31% by 6 months. Conclusion: PopKin suggests osimertinib delays recurrence rather than preventing it. Combined chemo analyses suggest chemo converts 15% of patients from rapidly to slowly recurring, but many “shifted” patients eventually recur. Hence, chemo may induce reversible tumor senescence rather than eradicating micrometastases. Anti-senescent cell strategies might prove beneficial. Frequent scans are warranted in the 1st postoperative year for early detection of recurrences. Table 1. EDNLRA of adjuvant chemo and control DFS and OS curves Arm Overall t1/2 a % Fastb Fast group t1/2 c % Slowd Slow group t1/2 e Control DFS 40.1 57 11.0 43 212.7 Chemo DFS 47.2 42 11.7 58 120.8 Control OS 51.9 69 25.8 31 1.3 x 1012 Chemo OSf 61.4 75 45.9 25 1.3 x 1012 aMedian t1/2 (half-life, months) on 1-phase decay EDNLRA. bMedian % of all patients in rapidly recurring/dying subgroup on 2-phase decay EDNLRA. cMedian t1/2 in rapidly recurring/dying subgroup on 2-phase decay EDNLRA. dMedian % in slowly recurring/dying subgroup. eMedian t1/2 in slowly recurring/dying subgroup. fIn 1 study, OS curve did not fit a 2-phase decay model Citation Format: David J. Stewart. Population kinetics (PopKin) of non-small cell lung cancer (NSCLC) adjuvant therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6299.

Preoperative durvalumab (D) with or without tremelimumab (T) for resectable head and neck squamous cell carcinoma (HNSCC): Updated results with high dimensional profiling of circulating immune cells.

6072 Background: Although PD-1 blockade has improved survival in patients with recurrent and/or metastatic HNSCC, safety and efficacy of neoadjuvant immunotherapy with PD-L1 inhibitor with or without CTLA-4 inhibitor has not been investigated. Here, we report the updated results of the safety and efficacy of a preoperative D with or without T (D+/-T) in patients with resectable HNSCC, accompanied with high dimensional profiling of circulating immune cells. Methods: Patients with locally advanced but resectable HNSCC were eligible. Enrolled patients were randomized into D or D+T, stratified by primary site and human papilloma virus (HPV) infection status. A single dose of preoperative D (1500mg) or D+T (1500mg+75mg) was administered, with surgery planned 2 to 8 weeks later for curative resection. Postoperative (chemo) radiation was prescribed based on standard guidelines, followed by maintenance with D every 4 weeks for 1 year. Dynamic changes in circulating immune cells were tracked with mass cytometry. The primary objective was to determine the local recurrence rate. Secondary endpoints included pathologic response, safety, survival outcome, and exploration of immune dynamics. Results: As of January 25th 2022 for the interim analysis, a total of 45 patients were completely enrolled and received surgical resection (D: 21 patients, D+T: 24 patients). Oropharyngeal cancer was most common (n = 23; 51.1%) and HPV-mediated cancer was observed in 20 patients (44.4%). Neoadjuvant D+/-T had acceptable safety profiles and was not associated with delays in surgery or unexpected adverse events. Tumor shrinkage was observed in 31 patients (68.9%), with 15.6% of average tumor shrinkage (range; 100.0% to -80.0%). Major pathologic response (no more than 10% of viable tumor cells) was achieved in 3 patients (6.7%), including 2 cases with pathologic complete response (4.4%). During median follow-up duration of 407 days after surgery, local recurrence and systemic recurrence were documented in 9 patients (20.0%) and 7 patients (15.6%), respectively. Median disease-free survival and overall survival was 910 days and not reached, respectively. High dimensional immune profiling with mass cytometry revealed that D+T disproportionally increased the frequency of regulatory T cells accompanied with the upregulation of their functional markers, which was absent in patients treated with D monotherapy. Conclusions: These updated data suggested that preoperative D+/-T was safe and feasible and had the potential to provide clinical benefits for patients with resectable HNSCC. Distinct immunologic changes in circulating immune cells were induced by each treatment regimen, warranting further investigation. The trial is ongoing and the updated outcomes with immune correlates will be presented in this ASCO. Clinical trial information: NCT03737968.

Quality of Life Is Associated With Survival in Patients With Gastric Cancer: Results From the Randomized CRITICS Trial.

The evaluation of health-related quality of life (HRQoL) in clinical trials has become increasingly important because it addresses the impact of treatment from the patient's perspective. The primary aim of this study was to investigate the effect of postoperative chemotherapy and chemoradiotherapy (CRT) after neoadjuvant chemotherapy and surgery with extended (D2) lymphadenectomy on HRQoL in the CRITICS trial. Second, we investigated the potential prognostic value of pretreatment HRQoL on event-free survival (EFS) and overall survival (OS). Patients in the CRITICS trial were asked to complete HRQoL questionnaires (EORTC Quality-of-Life Questionnaire-Core 30 and Quality-of-Life Questionnaire gastric cancer-specific module) at baseline, after preoperative chemotherapy, after surgery, after postoperative chemotherapy or CRT, and at 12 months follow-up. Patients with at least 1 evaluable questionnaire (645 of 788 randomized patients) were included in the HRQoL analyses. The predefined endpoints included dysphagia, pain, physical functioning, fatigue, and Quality-of-Life Questionnaire-Core 30 summary score. Linear mixed modeling was used to assess differences over time and at each time point. Associations of baseline HRQoL with EFS and OS were investigated using multivariate Cox proportional hazards analyses. At completion of postoperative chemo(radio)therapy, the chemotherapy group had significantly better physical functioning (P=.02; Cohen's effect size = 0.42) and less dysphagia (P=.01; Cohen's effect size = 0.38) compared with the CRT group. At baseline, worse social functioning (hazard ratio [HR], 2.20; 95% CI, 1.36-3.55; P=.001), nausea (HR, 1.89; 95% CI, 1.39-2.56; P<.001), worse WHO performance status (HR, 1.55; 95% CI, 1.13-2.13; P=.007), and histologic subtype (diffuse vs intestinal: HR, 1.94; 95% CI, 1.42-2.67; P<.001; mixed vs intestinal: HR, 2.35; 95% CI, 1.35-4.12; P=.003) were significantly associated with worse EFS and OS. In the CRITICS trial, the chemotherapy group had significantly better physical functioning and less dysphagia after postoperative treatment. HRQoL scales at baseline were significantly associated with EFS and OS.

Feasibility study of TAS-118 plus oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).

205 Background:TAS-118 (S-1 and leucovorin) + oxaliplatin (L-OHP) improved overall survival (OS) compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC) (Kang, Lancet Oncol. 2020). This study investigated the feasibility of peri (pre and post)-operative (op) chemotherapy (chemo) with TAS-118 ± L-OHP in pts with locally advanced resectable GC. While it was reported that pre-op TAS-118 + L-OHP followed by D2 gastrectomy was well tolerated and showed promising efficay (Takahari, ASCO-GI. 2020), the recommended post-op chemo regimen, TAS-118 or TAS-118 + L-OHP, has yet to be determined. Methods:Eligible pts with GC of clinical T3-4N1-3M0 were enrolled. The protocol treatment consisted of pre-op chemo with 4 courses of TAS-118 (40-60 mg/body, orally, twice daily, 7 days) + L-OHP (85 mg/m2, intravenously, day 1) in a 2-week cycle, and gastrectomy with D2 lymphadenectomy, followed by post-op chemo with 12 courses of TAS-118 (step 1) and 8 courses of TAS-118 + L-OHP (step 2). Step 2 was started if the dose-limiting toxicity (DLT) occurred in &lt; 6 of 10 pts in step 1. Up to 20 pts were included in the analysis of feasibility after a recommended regimen was determined. Results:Between December 2016 and February 2019, 45 pts were enrolled. The numbers of pts with cT3/4a and cN1/2/3 were 13/32 and 25/17/3, respectively. Excluding 14 pts (4 achieving pathological complete response, 4 not satisfying the criteria for post-op chemo, 3 physician judgement or pt withdrawal, 2 progressive disease, 1 adverse event [AE]), 31 pts (11/20 in step 1/2) received the post-op chemo. No DLT was observed in either step. The post-op chemo completion rate was 90.9% (95% CI, 63.6-99.5) in step 1 and 80.0% (95% CI, 59.9-92.9) in step 2. The median relative dose intensity of TAS-118 in step 1 was 83.3%, and those of TAS-118 and L-OHP in step 2 were 69.9% and 74.3%, respectively. One pt in step 2 discontinued post-op chemo due to AE. Grade ³ 3 AEs observed in ≥ 10% of pts were weight loss in both step 1 and step 2 (2 in each), and hypokalemia (n = 3) and neutropenia (n = 2) in step 2. At 1-year follow-up after the last pt was enrolled, recurrence-free survival and OS rates were 91.1% (95% CI, 78.0-96.6) and 100%, respectively at 12 months, and 69.1% (95% CI, 49.6-82.3) and 95.5% (95% CI, 71.9-99.3), respectively at 24 months. Conclusions:Taken together with the feasibility and efficacy of pre-op chemo, peri-op chemo with TAS-118 + L-OHP with D2 gastrectomy was well tolerated and showed promising efficacy. Clinical trial information: UMIN000024688.

Sexuality of Women after Gynecological Surgeries.

(1) Background: Disorders of sexual life negatively impact self-esteem and social relationships. This problem affects patients after gynecological surgery. Providing access to specialist sexologist care constitutes an important aspect of support for this patient group. (2) Objective: The aim of the study was to assess the sexual life of women depending on the time since surgery, extent of gynecological surgery and postoperative chemotherapy and/or radiotherapy. (3) Methods: The study included 136 patients from gynecological outpatient clinics in Szczecin, Poland. The women answered questions from a special three-part questionnaire. Participation was anonymous and voluntary. The data obtained in the survey were subject to statistical analysis. (4) Results: Among patients with a sparing of the cervix, most have never or almost never experienced discomfort or pain during intercourse, and believe that the quality of their sex life has not deteriorated after surgery. It was found that cervical removal, despite the existence of other conditions, increases the chance of pain during sexual activity 11 times. We found that the removal of adnexa did not increase the risk of changing sexual activity. In patients who had not undergone postoperative chemo- and/or radiotherapy, sexual activity did not change after surgery, and they never or almost never experienced discomfort or pain during intercourse. On the other hand, it was shown, despite the smaller study group, that patients treated with postoperative chemo- and/or radiotherapy did not initiate sexual intercourse. (5) Conclusion: The more extended the gynecological surgery of the uterus, the greater the limitation of sexual life.

Abstract P6-10-13: Associated ductal carcinoma in situ in primary operated TNBC is associated with a longer time to distant event

Abstract Purpose We studied presence of accompanying ductal adenoma in situ (accom-DCIS) in a consecutive series of primary operated TNBC for distant time-to-event outcome. Methods A retrospective cohort study (diagnosis 1/1/2000 - 31/12/2017) of prospectively registered primary operated TNBC patients in UZ Leuven. Only TNBC of no special type were included. We compared patient (age, BMI, symptomatic/screening-detected) and tumor related factors (Nottingham Prognostic Index (NPI), Lymphovascular Involvement (LVI)) for accom-DCIS and analyzed the effect of accom-DCIS on distant time to event outcome using the Cox proportional hazards model. Multivariate models were used to correct for possible confounders. Results We included 524 patients. Median follow-up was 102 months. Mean age of patient was 57.3 [26-90] years and 361 had accom-DCIS (68,9 %); demographics, clinical-pathological characteristics and postoperative chemo- and radiotherapy were similar in patients with and without accom-DCIS; only LVI was significantly more likely to be present in accom-DCIS cases (p=&amp;lt;0.001). There were no differences in distant relapse rate (16.6% in accom-DCIS group vs 12.9% in no DCIS group [HR = 1.350, 95% CI (0.817;2.248) p=0.239]. Time to distant event was later if accom-DCIS was present: Mean time to distant event was 2.72yrs in the accom-DCIS group and 1.61yrs in the group with absent DCIS. In accom-DCIS 20/63 (31.8%) distant relapses occurred after 3 years while only 1/21 distant relapse (4.8%) occurred after 3 years in the non-DCIS group [HR =6.667, 95% CI (0.952-46.705) p=0,029]. Conclusion In our series of TNBCs, patients with and without accom-DCIS had similar distant relapse rates. Significantly more distant relapse occurred after 3 years in patients with accom-DCIS compared to patients without accom-DCIS. Citation Format: Jan Ardui, Hans Wildiers, Giuseppe Floris, Hava Izci, Kevin Punie, Tatjana Geukens, Els Van Nieuwenhuysen, Sileny Han, Patrick Berteloot, Annouschka Laenen, Hilde Janssens, Ann Smeets, Caroline Weltens, Ignace Vergote, Patrick Neven. Associated ductal carcinoma in situ in primary operated TNBC is associated with a longer time to distant event [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-10-13.

Dose-dense early postoperative intraperitoneal chemotherapy in ovarian cancer: Randomized, phase II trial.

5514 Background: Dose-dense early postoperative intraperitoneal chemo (DD-EPIC) had been carried out in advanced ovarian cancer (OC) pts in China over the past three decades but it was not proved by a prospective study. This trial was designed to confirm the benefit of DD-EPIC in delaying progression and improving survival. Methods: In a multicenter, phase 2 trial, pts with FIGO IIIC-IV OC and optimal debulking surgery (residual disease ≤1cm) were randomly allocated to receive 4 doses of weekly DD-EPIC with cisplatin (50mg/m2) and etoposide (100mg/m2) followed by 6 cycles of intravenous (iv) chemo with carboplatin and taxane every 3 weeks (DD-EPIC group), or standard iv chemo alone (iv group). (ClinicalTrials.gov, NCT01669226). Results: Between 2009 and 2015, 218 pts were randomized, of whom 215 initiated treatment (106 to DD-EPIC and 109 to iv; for efficacy analyses). Totally, 36 pts (16·7%) were received neoadjuvant chemo. With a median of 61·9 mos follow-up, 122 pts died (54 in DD-EPIC and 68 in iv group). Remarkable OS benefit of DD-EPIC was recorded (67·5 mos for DD-EPIC vs. 46·3 mos for iv; HR 0·70, 95% CI 0·49-1·00, P=0·047). Pts in DD-EPIC had a significantly increased median PFS compared with those in iv group (21·7 vs. 16·8 mos; HR 0·64, 95% CI 0·47-0·86, P=0·003). Median TFST was 25·1 vs. 18·0 mos in favor of DD-EPIC (HR 0·62, 95%CI 0·46-0·83, P=0·002). Similar findings were detected in TSST (42·2 vs. 29·3 mos; HR 0·66, 95%CI 0·47-0·94, P=0·019). Grade 3 and 4 Leucopenia (53·8% vs. 35·2%), anemia (23·6% vs. 5·6%) and gastrointestinal events (10·4% vs. 1·9%) were more common in DD-EPIC ( P=0·006, P&lt;0·001 and P=0·010, respectively). Ninety-one pts were detected by gBRCA testing, with 25·3% of cases carrying deleterious BRCAm, but PFS and OS benefit were observed in patients with BRCA-wild type (HR 0·46 and 0·55, 95%CI 0·27-0·81 and 0·27-1·11, respectively). Conclusions: DD-EPIC with a higher completion rate and acceptable treatment burden was associated with longer OS than standard iv alone. Owing to the benefit of relatively long-term OS, DD-EPIC may be considered as a valuable option for OC, particularly in developing countries and BRCA-wild type pts. Clinical trial information: NCT01669226. [Table: see text]

Retrospective analysis of clinical profile of pediatric proptosis in a tertiary care hospital of Eastern India

Background: Pediatric proptosis can often present with puzzling clinical features and needs a systematic approach to avoid diagnostic dilemma. Aims and Objectives: To study the clinical and etiological profile, management, and outcome of pediatric proptosis. Materials and Methods: This retrospective noncomparative study involved the analysis of record files of 41 cases of childhood proptosis, who presented in the eye outpatient department and oculoplastic clinic between January 2013 and December 2016. Results: There were a total of 41 children, age varied from 6 months to 15 years. The maximum number of cases 25 (61%) were in the age group of 0–5 years. Male:female ratio was 1.77:1. Unilateral cases were found to be 31 (76%) and bilateral cases be 10 (24%). Neoplastic lesions constituted 22 (54%) of which benign lesions were 3 (14%) and malignant were 19 (86%). Among malignant, primary were 11 (58%) and secondary were 8 (42%). Inflammatory/infective lesions were 8 (20%). Conservative/medical management was given to 11 cases (27%). Surgery with pre- or post-operative chemo- or radio-therapy was the treatment of choice. Conclusion: Neoplastic lesions were found to the most common cause of proptosis in this study. Apart from detail ocular and systemic examination, final etiological diagnosis is possible in certain cases only after investigations such as peripheral smear, bone marrow examination, histopathological examinations, ultrasonography B-scan, computed tomography scan, and magnetic resonance imaging. Timely diagnosis and management can save the vision and many a times lives.

Risk prediction model for disease-free survival in women with early-stage cervical cancers following postoperative (chemo)radiotherapy.

To investigate disease-free survival (DFS) and prognostic factors following the administration of postoperative (chemo)radiotherapy in patients with early-stage cervical cancers. The medical records of 1,069 patients from 10 participating institutions were reviewed. Statistically and clinically established factors were considered as candidates for constructing the prediction model. This model was validated, using bootstrapping to correct for optimistic bias. The 5-year DFS rate was 81.1%, with a median follow-up period of 59.6 months. The statistically significant prognostic factors were as follows: pelvic lymph node metastasis, histologic type, parametrial invasion, lymphovascular space invasion, and tumor size. The nomogram for DFS was constructed, and it demonstrated a good discrimination performance, with an internally validated concordance index of 0.72. Our predictive model exhibited accurate predictions and may be useful in designing clinical trials to study if further chemotherapy can reduce the recurrence of disease in high-risk patients.

PRIMARY SQUAMOUS CELL CARCINOMA OF THE THYROID GLAND - CASE REPORT AND REVIEW OF THE LITERATURE

Background Primary squamous cell carcinoma of the thyroid gland (PSCTC) is a rare malignancy, but demonstrates a very aggressive behaviour and has a poor prognosis. The best treatment is radical surgery and postoperative chemo- and radiotherapy, although there are some reports that this tumour is resistant to conservative therapy. Patients often present with a large tumour mass on the neck with a solid consistency. Diagnosis is usually set during the operation - on a frozen section. Case report We present a case of a 71-year old man with weight loss and rapidly growing neck mass for the last two months. MRI showed a tumour of the left lobe of the thyroid gland, compressing the trachea and the adjacent structures. A left thyroidectomy with isthmectomy has been performed. Frozen section showed primary squamous cell carcinoma. Tumour recurrence two months later led to the second operation with the same effect. The patient died in a couple of months. Conclusion Because of its rarity and poor biology, treatment of PSCTC remains unsatisfactory. There are still many challenges on its origin, behaviour and prognostic factors. The results of postoperative chemo- or radiotherapy are controversial.

P2.01-083 Prognostic Factors of Overall Survival in 150 Resected Lung Adenocarcinoma Patients

The 2011 IASLC/ATS/ERS pathological classification of pulmonary adenocarcinoma(ADC) gives new direction to clinical individualized treatment strategies and prognostic evaluation. We analyzed the prognostic effect of invasive ADC sub-types according to the new classification system. 150 invasive lung ADCs resected in West China Hospital from 2008 to 2013 was analyzed in 5% increments, and classified and graded according to their predominant patterns, as proposed by the IASLC/ATS/ERS. Clinical data, including smoking status, chemotherapy/ radiotherapy after surgery and patient outcomes were collected. Overall survival was evaluated. Tumor necrosis (p=0.033), poor differentiation (p=0.027), lymph node metastasis (p<0.001), surgical procedures (p=0.010), tumor diameter (p<0.001), and TNM stage (p<0.05） were significantly associated with overall survival (OS). Solid predominant ADCs (SPA) had a shorter OS than non-SPAs (43.5 vs 65.3 months, p=0.014). High-risk group (including SPA and micro-papillary predominant ADCs, MPA for short) had a poorer prognosis than low-risk group (including lepidic predominant, acinar predominant and papillary predominant ADCs, LPA, APA and PPA for short respectively) (44.4 vs 65.1 months, p=0.025). ADCs with papillary growth patterns (PP) had a better OS than those without PP (67.1 vs 42.5 months, p=0.001). In patients treated with chemo-or radiotherapy after surgery, OS of SPA and ADCs with PP were comparable to that of non-SPA and ADCs without PP, respectively (p value>0.05). Smoking also increased the risk of poor OS in certain subtypes significantly. Multivariate analysis showed SPA, high-risk group and ADCs with PP were independent prognosis factors for OS. Growth pattern and grading system are effective prognosticators of OS in invasive lung ADCs, which also influenced by other factors like post-operative chemo-/radio-therapy and smoking status. These results will give an instruction to the future individualized treatment of lung ADCs.

Carcinomes intra-osseux primitifs des mâchoires de novo (type 3)

Primary intraosseous carcinoma (PIOC) of the jaws is a rare epidermoid carcinoma from epithelial origin and initially strictly localized within the bone. Histologically, type 3 PIOC (PIOC3) is a de novo primary intraosseous carcinoma. Because of the rarity of this illness, we propose an analysis of a personal case and a revue of the literature. Two search engines (Pubmed®, Sciencedirect®) were questioned over the period 1976-February 2016 by using following keywords carcinoma, intraosseous, jaws, squamous cell carcinoma. Articles reporting proven PIOC3 and mentioning a precise treatment were selected. Thirty articles concerning 54 patients (sex ratio: 2.4; mean age: 56.8; extreme: 24-78) met the inclusion criterions. The most common symptoms were swelling (53%), pain (44.9%) and infra-alveolar nerve paresthesia (30.6%). The time to diagnosis was 13 weeks. Classification of Zwetyenga et al. showed more than 80% of T2 and T3 stages. The lesions were predominantly mandibular (85.2%) and posterior. Less than a third of patients had lymph node and 10% had distant metastasis. Treatment consisted mostly in a combination of surgery and radiotherapy. With a mean follow-up of 74.8 months, 70.8% were in remission with no evidence of recurrence. We report the case of a 58-year-old patient, with no medical history, complaining since several months about periodontitis with teeth mobility in the right mandibular area. The panoramic X-ray showed a bone lysis at the place of tooth No.46. In the absence of alveolar healing after extraction and antibiotherapy, a biopsy was made that diagnosed a differentiated keratinizing squamous cell carcinoma. CT scan and MRI showed a mandibular cortical bone loss with involvement of adjacent structures and lymphadenopathy in the ipsilateral IB area. The patient was treated with a combination of chemotherapy and surgery. Postoperative chemo- and radiotherapy is still going on. The PIOC3 is a rare tumor, mainly arising in males around 50. Diagnosis should be evoked in the presence of painful swelling and nervous symptoms. The time to diagnosis is long. Tumors are usually seen at late stages. Treatment classically combines surgery and radiotherapy.

PO84WHOLE BRAIN RADIOTHERAPY (WBRT) FOLLOWING RESECTION OF BRAIN METASTASES: WHO DECIDES? AN AUDIT OF OUTCOMES AND CLINICIAN CONFIDENCE

INTRODUCTION: Whole brain radiotherapy (WBRT) following brain metastases resection improves intra-cranial disease control without improving overall survival (OS). Expanding treatment options mean the role of WBRT should be individualised. We undertook a study to determine the rates and outcomes of post-op WBRT and the confidence of site-specific oncologists (e.g. breast, lung) in decision-making in this field. METHOD: Demographics and outcomes of patients who had brain metastases resected between 04/12 - 04/14 were retrospectively collected. Consultant opinion was collated via an on-line survey. RESULTS: 97 patients were identified (primary sites: lung 34%, breast 24%, colorectal 14%, renal 7%, melanoma 4%, others 17%). 68 (70%) underwent WBRT; it was omitted in 29 patients (21: too unwell/progressive disease, 5: previous cranial RT, 2: post-op chemo, 1: unknown). Median time to WBRT: 5.7 weeks, range 1-15.7 weeks. WBRT commenced >6 weeks post-op in 34%, with variation between disease groups. Median OS was 12.2 and 4.8 months in the WBRT and non-WBRT groups respectively. Intracranial progression was confirmed on imaging in 32% of patients in the WBRT group (73% local recurrence, 27% distant) and 45% in the non-WBRT group (69% local, 31% distant). For the whole group, 12 month OS was 40.8%, 24 month 21.5%. 78% (28/36) of survey respondents thought that decisions on WBRT use should be made by the neuro-oncology MDT. Only 14% felt completely confident in decision making and 11% very familiar with evidence in this field. CONCLUSION: WBRT is rarely electively withheld in our unit. There is scope to improve post-resection decision-making, pathways and education. Neuro-oncology MDTs play an important role in in this area.

Salivary gland adenoid cystic carcinoma.

Malignant fibrous histiocytoma, also known as pleomorphic undifferentiated sarcoma not otherwise specified, arises in numerous organs. The first-line treatment is complete excision of the mass, but in some cases postoperative chemo- and/or radiotherapy is recommended. Only a few cases of malignant fibrous histiocytoma of the vocal fold have been previously reported in the literature. We report a new case, which originated in the true vocal fold of a 65-year-old man. The mass was removed via CO2 laser excision with preservation of the vocal fold and without the need for further treatment. At 3 years of follow-up, the patient remained recurrence-free.

Validating a local failure risk stratification for use in a prospective study of adjuvant radiation in bladder cancer.

347 Background: To inform the design of trials of adjuvant radiation (RT) for bladder cancer, a local failure (LF) risk grouping has been proposed and externally validated that stratifies radical cystectomy (RC) pts into 3 groups based on pathologic factors. This stratification was developed using historical surgical databases and may not reflect outcomes in the observation arm of a modern trial. The purpose of the study is to assess whether trial accrual bias or improving surgical techniques over time impact the validity of the stratification or reduce the LF risk estimates for each subgroup. Methods: The LF stratification was developed using 2 cohorts treated with RC +/- chemo: a single-institution cohort of 442 pts (1990-2008) and the multi-center SWOG 8710 cohort of 264 pts (1987-1998). To assess the impact of trial accrual bias, we excluded pts who developed LF, DM, died, or were lost to follow up &lt;90 days from surgery or completing post-op chemo as these pts are very unlikely to be enrolled in an adjuvant RT trial. 3-yr LF rates were estimated using Gray’s test. The stratification was considered valid if all 3 risk groups had significantly different LF rates. To assess the impact of improving surgical techniques over time, a Fine-Gray regression estimated the association of LF and year of RC while controlling for risk group. Results: Using the stricter criteria, 10% of SWOG pts and 14% from the other cohort were excluded. Analysis of the remaining pts confirmed 3 subgroups with significantly different LF risk: low risk (stage ≤pT2), intermediate risk (≥pT3 with negative margins and ≥10 nodes identified at surgery), and high risk (≥pT3 with positive margins OR &lt;10 nodes identified) with 3-yr LF rates of 7%, 17%, and 36%, respectively (p&lt;0.01), nearly identical to the rates when not accounting for accrual bias. Year of RC was not associated with LF risk on univariate analysis or after controlling for risk group in the SWOG, single-institution, or combined cohorts. Conclusions: These results suggest that neither trial accrual bias nor improvements in surgical techniques over time invalidate the LF risk stratification or substantially affect LF estimates. The proposed stratification is promising for use in adjuvant RT trials.

PO-063: Post-operative (chemo)radiotherapy for oral cavity squamous cell carcinoma: outcomes and patterns of failure

PO-063: Post-operative (chemo)radiotherapy for oral cavity squamous cell carcinoma: outcomes and patterns of failure

Presentation and management of pulmonary artery sarcoma.

BackgroundPulmonary artery sarcoma (PAS) is a rare but aggressive malignancy that leads to heart failure and death without treatment. Here we reviewed the presentation and management of patients treated at a national centre for pulmonary endarterectomy (PEA) and its associated hospital in Cambridge, UK.MethodsDetails of PAS patients treated at Papworth and Addenbrooke’s Hospitals between 2000 and 2014 were reviewed.ResultsTwenty patients were diagnosed with PAS (11 males, 9 females), with a median age of presentation of 57 years (range 27–77). Presenting symptoms include dyspnoea (20), chest pain/tightness (7), oedema (5), constitutional symptoms (5), cough (3) and haemoptysis (3). Twelve patients were in group III/IV of the NYHA functional classification of symptoms. Initial CT scans were suggestive of thromboembolism in seven patients. Histological findings were of intimal sarcoma (13) and high grade sarcoma NOS (6).Median overall survival (OS) was 17 months. Fourteen patients underwent PEA to relieve vascular obstruction, while six had inoperable and/or metastatic disease. There were three peri-operative deaths. Although there was no difference in median OS between patients who had PEA and those who did not (20 vs 17 months, P = 0.2488), surgery provided significant symptomatic improvement and some with long-term survival. Five patients received post-surgical chemotherapy (anthracycline +/− ifosfamide), and after completion four also had radiotherapy. Patients who received post-operative chemo- and radio-therapy showed a trend towards better survival compared to those who had surgery alone (24 vs 8 months, P = 0.3417). For palliative chemotherapy, partial responses were observed with the VID regimen and pegylated liposomal doxorubicin. Stable disease was achieved in a patient with intimal sarcoma with rhabdomyosarcomatous differentiation on third-line cisplatin and topotecan. The longest surviving patient (102 months) has had PEA, adjuvant epirubicin and radiotherapy. She developed lung metastases 7 years later, which were treated with radiofrequency ablation.ConclusionsPAS often presents with symptoms mimicking pulmonary hypertension, heart failure or thromboembolic disease. PEA provides good symptomatic relief and in some cases, offers a chance of long-term survival. Although outcome appears to be better when PEA is combined with post-operative chemo- and radio-therapy, further studies are warranted.

Steward-Treves syndrome in a male patient

Lymphangiosarcoma is an uncommon vascular tumor that usually develops in chronic lymphedema. The etiology of lymphangiosarcoma remains unknown. It develops mainly after mastectomy, in association with chronic lymphedema (Stewart-Treves syndrome), or after radiotherapy. The early diagnosis of this aggressive tumor is important, as it has a high risk of local recurrence and metastasis. Stewart–Treves syndrome occurs in 0.5% of patients who survive mastectomy for more than 5 years. The mean age at appearance of the angiosarcoma is 62 years, and the mean interval between mastectomy and the appearance of the tumour is 10.5 years. Only two cases have been reported in men following mastectomy. We present a 70-year old male patient with lymphangiosarcoma which developed three and a half years after the diagnosis of breast carcinoma. The patient underwent mastectomy of the right mammary gland with ipsilateral axillary lymph node dissection and had postoperative chemo- and radiotherapy.