Trimodality Therapy In Patients Research Articles

Predictors of trimodality therapy in patients with muscle-invasive bladder cancer and effect on survival.

Due to its unique advantages over radical cystectomy (RC), trimodality therapy (TMT) is increasingly being utilized by patients diagnosed with muscle-invasive bladder cancer (MIBC) who are not suitable for or refuse RC. However, achieving a satisfactory oncological outcome with TMT requires strict patient selection criteria, and the comparative oncological outcomes of TMT versus RC remain controversial. Patients diagnosed with non-metastatic MIBC who underwent TMT or RC were identified from the SEER database during 2004-2015. Before one-to-one propensity score matching (PSM), logistic regression was utilized to identify predictors of TMT. After matching, K-M curves were generated to estimate cancer-specific survival (CSS) and overall survival (OS) with log-rank to test the significance. Finally, we conducted univariate and multivariate Cox analyses to identify independent prognostic factors for CSS and OS. The RC and TMT groups included 5812 and 1260 patients, respectively, and the TMT patients were significantly older than the RC patients. Patients with advanced age, separated, divorced, or widowed (SDW) or unmarried marital status (married as reference), and larger tumor size (< 40mm as reference) were more likely to be treated with TMT. After PSM, TMT was found to be associated with worse CSS and OS, and it was identified as an independent risk factor for both CSS and OS. MIBC patients may not be carefully evaluated prior to TMT, and some non-ideal candidates underwent TMT. TMT resulted in worse CSS and OS in the contemporary era, but these results may be biased. Strict TMT candidate criteria and TMT treatment modality should be required.

Trimodality therapy for patients with stage III non-small-cell lung cancer: A comprehensive surveillance, epidemiology, and end results analysis

PurposeDebate exists regarding the optimal management for patients with stage III non-small-cell lung cancer (NSCLC). Recent inclusion of chemotherapeutic data in the Surveillance, Epidemiology, and End Results (SEER) database has made it possible to identify patients with NSCLC who received chemotherapy. We hypothesized that patients with stage III NSCLC experience improved overall survival from trimodality therapy (TMT) versus definitive chemoradiation therapy (CRT) alone. Materials and MethodsWe analyzed the overall survival of stage III NSCLC patients based on the receipt of TMT versus CRT alone. This included crude and adjusted univariate models as well as crude and doubly robust adjusted multivariable analyses, both utilizing propensity score matching and inverse probability of treatment weighting. Factors included in the multivariable analyses included: age, sex, marital status, income, date of diagnosis, primary site, histology, grade, T stage, N stage, and intended treatment. Planned subset analyses were performed for stage III(N2) patients. ResultsAdult patients with stage III NSCLC (N = 9008) from the SEER database were included in our analyses. In our univariate analyses, an overall survival benefit was observed for TMT versus CRT (CrudeHR = 0.58, 95% CI = 0.55–0.61, p < 0.001; AdjHR = 0.58, 95% CI = 0.54–0.61, p < 0.001). This persisted in both crude and doubly robust multivariable analyses (CrudeHR = 0.57, 95% CI = 0.53–0.61, p < 0.001; AdjHR = 0.56, 95% CI = 0.53–0.59, p < 0.001). Patients with stage III(N2) disease also demonstrated a significant benefit to OS with TMT versus CRT alone. ConclusionThe significant difference in overall survival seen with TMT suggests this may be an effective treatment approach for select patients.

Induction versus no induction chemotherapy before neoadjuvant chemoradiotherapy and surgery in oesophageal adenocarcinoma: a multicentre randomised phase II trial (NCCTG N0849 [Alliance

Aimreport primary results from the first multicentre randomised trial evaluating induction chemotherapy prior to trimodality therapy in patients with oesophageal or gastro-oesophageal junction adenocarcinoma. Notably, recent data from a single-institution randomised trial reported that induction chemotherapy prolonged overall survival (OS) in patients with well/moderately differentiated tumours. MethodsIn this phase 2 trial (28 centres in the U.S. NCI-sponsored North Central Cancer Treatment Group [Alliance]), trimodality-eligible patients (T3-4N0, TanyN+) were randomised to receive induction (docetaxel, oxaliplatin, capecitabine; Arm A) or no induction chemotherapy (Arm B) followed by oxaliplatin/5-fluorouracil/radiation and subsequent surgery. The primary endpoint was the rate of pathologic complete response (pathCR). Secondary/exploratory endpoints were OS and disease-free survival (DFS). ResultsOf 55 patients evaluable for the primary endpoint, the pathCR rate was 28.6% (8/28) in A versus 40.7% (11/27) in B (P = .34). Given interim results indicating futility, accrual was terminated, but patients were followed. After a median follow-up of 60.4 months, a longer median OS in Arm A versus B was unexpectedly observed (3-year rates 57.1% versus 41.7%, respectively) driven by longer DFS after margin-free surgery. In posthoc analysis, induction (versus no induction) chemotherapy was associated with significantly longer OS and DFS among patients with well/moderately differentiated tumours, but not among patients with poorly/undifferentiated tumours (Pinteraction = 0.037). ConclusionsAdding induction chemotherapy prior to trimodality therapy did not improve the primary endpoint, pathCR. However, induction chemotherapy was associated with longer median OS, particularly among patients with well/moderately differentiated tumours. These findings may inform further development of curative-intent trials in this disease.

Survival After Trimodality Therapy in Patients With Locally Advanced Esophagogastric Adenocarcinoma: Does Only a Complete Pathologic Response Matter?

To evaluate whether pCR exclusively defines major pathologic response to treatment with improved survival. pCR after trimodality therapy for EAC is infrequent but associated with improved prognosis. Yet most clinical trials and correlative studies designate pCR as the primary endpoint. We analyzed our prospectively maintained database for patients who underwent trimodality therapy for locally advanced esophageal adeno-carcinoma between 1995 and 2017. Overall survival (OS) was examined by percentage TR in the primary tumor bed and pathologic nodal stage (ypN0) using Kaplan-Meier plots. Optimal thresholds of TR for differentiating patients in terms of OS were investigated with descriptive plots using restricted cubic spline functions; associations were quantified using Cox multivariable analysis. Among 788 patients, median follow-up was 37.5 months (range, 0.4210.6); median OS was 48.3 months (95% CI, 42.2-58.8). Absence of residual nodal disease was independently associated with improved survival ( P < 0.001). Survival curves for 90% to 99% TR and 100% TR were similar, and a change in probability of improved OS was observed at 90% TR. On multivariable analysis, combining 90% to 99% and 100% TR was independently associated with improved OS, compared with 50% to 89% and <50% TR. ypN0 status is the strongest indicator of major pathologic response to trimodality therapy, in addition to >90% TR in the primary tumor bed. These findings may allow the definition of major pathologic response to be expanded, from pCR to > 90% TR and ypN0. This has meaningful implications for future clinical trials and correlative studies.

Definitive re-irradiation of locally recurrent esophageal cancer after trimodality therapy in patients with a poor performance status.

There are few treatment guidelines for locally recurrent esophageal cancer after trimodality treatment (pre-operative chemoradiation followed by surgery) in patients with a poor performance status. The purpose of this single institutional, retrospective study was to evaluate the clinical outcomes and toxicities of definitive-intent re-irradiation for patients with recurrent esophageal cancer with a poor performance status [ECOG (Eastern Cooperative Oncology Group) ≥2]. Seven patients were identified with a median age of 74 years (range, 61-81 years). Four patients were ECOG 2 and three patients were ECOG 3. The median follow-up time after re-irradiation was 49 months. The median interval between initial radiotherapy and re-treatment was 32 months. Six patients received concurrent chemotherapy [carboplatin + paclitaxel in three patients; folinic acid, fluorouracil, oxaliplatin (FOLFOX) + 5-fluorouracil in one patient; FOLFOX in one patient, and capecitabine in one patient]. At the last follow-up, the six patients who underwent concurrent chemotherapy had stable disease (86%), while the one who did not receive chemotherapy progressed (14%). Two patients developed metastases. Three patients developed acute (<6 months) grade 4 toxicities (dysphagia, anemia, esophagitis). There were no early deaths attributable to treatment. Late toxicities (>6 months) were limited to grades 1 and 2 dysphagia and pneumonitis in four patients. In conclusion, definitive re-irradiation of recurrent esophageal cancer in patients with a poor performance status appears to be safe with acceptable acute toxicity and late complications. It also appears to result in durable local control when combined with chemotherapy, albeit with a small number of patients and limited follow-up.

MP61-08 A PHASE I/II TRIAL OF TRANSURETHRAL SURGERY FOLLOWED BY A COMBINATION OF ATEZOLIZUMAB AN ANTI-PDL-1 (MPDL3280A) WITH TRIMODAL THERAPY IN PATIENTS WITH MUSCLE-INVASIVE BLADDER CANCER

INTRODUCTION AND OBJECTIVE: Bladder preserving strategies such as trimodality therapy (TMT) remain associated with suboptimal local control of muscle invasive bladder cancer (MIBC). Recently, immune checkpoint programmed death-ligand 1 therapy (PD-L1) has shown rapid and lasting responses in metastatic MIBC. Our aim was to evaluate safety and toxicity profile of concurrent Atezolizumab (anti-PDL-1) in combination with TMT in patients with MIBC. METHODS: Phase I/II non-randomized safety/efficacy study including T2-T4a N0M0 MIBC patients electing for bladder preservation therapy (NCT03620435). Patients were treated with a trans-urethral resection of bladder tumor (TURBT) followed by intensity modulated radiation therapy (IMRT) (50 Gy/20 fractions. 2.5 Gy per fraction – 5 times per week for 4 weeks), Gemcitabine (for 4 weeks at 100 mg/m2, IV once weekly) and Atezolizumab (1200 mg IV on day 1 of 3 week cycle). This trial recruited patients par block of 3 to assess dose related toxicity (DLT) in case of severe side effects the atezolizumab dose was reduced to 840mg. The primary endpoint was safety assessed using the national cancer institute-common terminology criteria for adverse events (NCI-CTCAE) version 4.03. RESULTS: Between December 2017 and January 2019, our study included 8 patients (6 males); median age was 68 (IQR 60; 70). Six patients were cT2 and 2 patients cT3. The first five patients received atezolizumab at 1200 mg and 3 of them developed grade 3 side effects (table 1). The atezolizumab dose was reduced to 840 mg for the 3 last. Study was terminated due to the presence of grade 3 side effects even with the reduced atezolizumab dose. No grade 4 side effects were observed. No deaths occurred. CONCLUSIONS: Concurrent administration of immune checkpoint inhibition with chemoradiation for MIBC was associated with unacceptable toxicity. These results do not support their concurrent use with trimodality therapySource of Funding: Sponsored by F. Hoffmann-La Roche Ltd

A multicenter study of trimodality therapy for patients 75 years and older with esophageal cancer.

131 Background: Trimodality therapy is the standard of care for patients with resectable cancer of the esophagus. However, patients ≥75 years have been underrepresented or excluded from landmark clinical trials to date. We investigated the feasibility and safety of treatment of esophageal cancer with trimodality therapy in patients’ ≥ 75 years. Methods: We performed a retrospective review of all patients ≥75 years who received trimodality therapy for esophageal cancer in 3 high volume tertiary cancer institutions from June 2007 to June 2013. All patients received neoadjuvant radiation with concomitant chemotherapy followed by esophagectomy. Toxicities and clinical outcomes were abstracted from the electronic medical record and partially from a prospectively maintained database. Overall and disease-free survival were estimated using the Kaplan-Meier method. Results: Five hundred seventy patients were treated with trimodality therapy for esophageal cancer from 2007-2013. Of these, 38 patients (7%) were 75 or older at the time of diagnosis. At diagnosis, comorbidities included coronary artery disease (32%), atrial fibrillation (11%) and COPD (13%). The majority of patients (87%) received 50.4Gy/28 fractions. 5-fluorouracil (5-FU)/cisplatin was the most common chemotherapy regimen (37%), followed by 5-FU/docetaxel (24%). A total of 13 patients (34%) developed acute grade ≥3 toxicity associated with neoadjuvant therapy. The most common acute grade 3 toxicities were haematological (10%), nausea (8%), esophagitis (5%) and fatigue (5%). Significant postoperative complications included respiratory (empyema, ARDS, pleural effusion) (39%), arrhythmia (32%), anastomotic leak (5%), and ileus (5%). There were 2 deaths (5%) within 90 days of surgery: one was secondary to empyema, the other developed DIC and sepsis. Median overall survival and disease free survival were 4.4 and 2.3 years respectively. Conclusions: Trimodality treatment is a reasonable approach for management of carefully selected elderly patients with esophageal cancer, with similar rates of cancer outcomes, and treatment related morbidity and mortality as compared to younger patients.

Radiation dose mapping and anastomotic complications after trimodality therapy for esophageal cancers

Background and purposeThere is conflicting evidence with respect to the correlation between neoadjuvant chemoradiation and anastomotic complications following trimodality therapy in patients with esophageal cancer. We aimed to analyze the relationship between their dosimetry and any resulting anastomotic complications. Materials and methodsThe medical records of 51 consecutive patients who underwent trimodality therapy between 2007 and 2014 were retrospectively reviewed. We analyzed the differences in the mean dose received by regions of the esophagus relative to the landmark of the azygous vein and the stomach to correlate the development of an anastomotic complication using nonparametric rank-sum tests. ResultsAnastomotic leakage and stricture rates were 12% and 22%, respectively. Patients with anastomotic complications received a statistically significant higher mean dose to the esophagus at the level of the azygous vein (0.0 cm) and lower (up to −2.7 cm) (28.4–42.2 Gy vs. 10.3–27.6 Gy, p < 0.04). There were no differences noted in mean gastric doses. Median follow up time was 30.9 months. Median overall survival and disease free survival of our patient cohort was 34.4 months and 22.5 months, respectively. The development of an anastomotic complication did not affect survival outcomes. ConclusionPatients who experienced anastomotic complication after trimodality therapy for esophageal cancer were more likely to have received a higher mean esophageal dose around the proximity of the azygous vein, where intrathoracic anastomoses most commonly occur. Communication between surgical and radiation oncologists regarding the anastomotic location may be an important consideration in planning for trimodality therapy in reducing potential anastomotic complications.

Comparison of bimodality versus trimodality therapy for esophageal or gastroesophageal junction (GEJ) cancer: Experience from the Princess Margaret Cancer Centre.

122 Background: There are no phase 3 trials comparing definitive chemoradiation (bimodality) versus. perioperative chemoradiation (trimodality) for locoregional esophageal/GEJ cancer. Methods: A retrospective analysis (2011-2015) compared bimodality and trimodality therapy in patients (pts) with locoregional esophageal/GEJ cancer treated with curative intent. Overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis. Uni- and multivariable Cox proportional hazards regression adjusted for patient and disease factors. Results: Of 108 patients, 82 (76%) were male. Mean ages were 69.5 ± 11.0 years (bimodality; N = 41) and 60.5 ± 11.1 years (trimodality; N = 67). For bimodality pts, 37% had adenocarcinoma and 63% had squamous cell carcinoma (SCC). For trimodality pts, 79% had adenocarcinoma and 21% had SCC (p &lt; 0.0001). Bimodality pts received a higher radiation dose compared to trimodality pts (50.1 ± 6.7 vs. 45.2 ± 6.4 Gy). Median follow-up was 49.3 months. We found no significant OS difference between bimodality (27.0 months) and trimodality therapy (29.8 months) in the overall cohort (p = 0.57) (4 year OS rate: 42% vs. 38%). In the subgroup with adenocarcinoma histology, trimodality therapy significantly improved OS and DFS compared to bimodality (OS: 31.8 vs. 10.4 months, hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.18-0.66, p = 0.001; DFS: 15.0 vs. 6.7 months; HR 0.39, 95%CI 0.21-0.73, p = 0.003). In the SCC subgroup, median OS and DFS were similar (OS: not reached vs. 29.2 months, p = 0.48; DFS: 27.0 vs. 24.0, p = 0.96). Using multivariable regression with AIC backward selection, the only retained prognostic factors were treatment modality (p = 0.06) and histology (p = 0.01). Conclusions: Our findings support preferential use of trimodality therapy for pts with adenocarcinoma histology given superior OS and DFS, whereas bimodality and trimodality therapy appeared comparable in pts with SCC histology. Pending confirmation in a larger series with longer follow-up, these findings suggest differential treatment algorithms for locoregional esophageal and GEJ cancer based on tumor histology.

Phase I Clinical Trial of Everolimus Combined with Trimodality Therapy in Patients with Muscle-Invasive Bladder Cancer.

Background: Local control following trimodality therapy (TMT) for muscle-invasive bladder cancer (MIBC) requires further optimization.Objective: Evaluating the biologic endpoint, feasibility, and toxicity of integrating everolimus to TMT in patients with MIBC.Methods: This was a phase I trial in patients with MIBC who were not surgical candidates or who refused cystectomy. Following maximal transurethral tumor resection, patients were treated by radiotherapy (50 Gy/20 fractions), gemcitabine (100 mg/m2/weekly) and escalating doses of everolimus (2.5–5.0 mg/day). Everolimus was given daily for one month prior to radiation, during treatment, and one month post-radiation. Toxicity assessment followed the Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring Criteria. Biologic endpoint with downregulation of phospho-S6 (pS6) was assessed using immunohistochemistry. Local response was evaluated with imaging and bladder biopsy post-therapy.Results: 10 patients were recruited; 8 males, 2 females. Median age was 78 years (range: 63–85). Four patients entered everolimus 2.5 mg cohort. Six other patients entered everolimus 5.0 mg cohort. Toxicities were encountered in 2 patients (Grade I), 6 patients (Grade II), 9 patients (Grade III) and 1 patient (Grade IV), with some experiencing more than one toxicity. Most Grade III and IV toxicities were encountered from everolimus alone prior to combination testing. Trial was terminated early due to toxicity. Interestingly, 6/10 patients (60%) achieved a complete response with negative post-treatment biopsies. Significant decrease of pS6 was demonstrated post-therapy (p = 0.03).Conclusions: Although combining everolimus with TMT achieved a biological endpoint and complete response in a significant number of patients with MIBC and negative prognostic factors, it was associated with unacceptable increased toxicity.

Improved Outcomes with Modern Lung-Sparing Trimodality Therapy in Patients with Malignant Pleural Mesothelioma

IntroductionHigher target conformity and better sparing of organs at risk with modern radiotherapy (RT) may result in higher tumor control and less toxicity. In this study, we compare our institutional multimodality therapy experience of adjuvant chemotherapy and hemithoracic intensity-modulated pleural RT (IMPRINT) with previously used adjuvant conventional RT (CONV) in patients with malignant pleural mesothelioma (MPM) treated with lung-sparing pleurectomy/decortication (P/D). MethodsWe analyzed 209 patients who underwent P/D and adjuvant RT (131 who received CONV and 78 who received IMPRINT) for MPM between 1974 and 2015. The primary end point was overall survival (OS). The Kaplan-Meier method and Cox proportional hazards model were used to calculate OS; competing risks analysis was performed for local failure-free survival and progression-free survival. Univariate analysis and multivariate analysis were performed with relevant clinical and treatment factors. ResultsThe median age was 64 years, and 80% of the patients were male. Patients receiving IMPRINT had significantly higher rates of the epithelial histological type, advanced pathological stage, and chemotherapy treatment. OS was significantly higher after IMPRINT (median 20.2 versus 12.3 months, p = 0.001). Higher Karnofsky performance score, epithelioid histological type, macroscopically complete resection, and use of chemotherapy/IMPRINT were found to be significant factors for longer OS in multivariate analysis. No significant predictive factors were identified for local failure or progression. Grade 2 or higher esophagitis developed in fewer patients after IMPRINT than after CONV (23% versus 47%). ConclusionsTrimodality therapy including adjuvant hemithoracic IMPRINT, chemotherapy, and P/D is associated with promising OS rates and decreased toxicity in patients with MPM. Dose constraints should be applied vigilantly to minimize serious adverse events.

Results of a phase I-II trial using tri-modality therapy in patients with post-prostatectomy high risk pathologic (p) T2-3N0M0 prostate cancer.

e16620Background: A phase I-II trial was conducted to determine the safety and feasibility of post-prostatectomy radiation therapy (RT), concurrent docetaxel and hormonal therapy (HT) in patients w...

Preliminary Results of a Nearly Completed Phase 1-2 Trial Using Trimodality Therapy in Patients With Post Prostatectomy High-Risk Pathologic (p) T2-3N0M0 Prostate Cancer

Preliminary Results of a Nearly Completed Phase 1-2 Trial Using Trimodality Therapy in Patients With Post Prostatectomy High-Risk Pathologic (p) T2-3N0M0 Prostate Cancer

The Prognostic Impact of Preoperative and Postoperative Chemoradiation in Clinical Stage II and III Esophageal Squamous Cell Carcinomas: A Population Based Study in Taiwan.

While preoperative chemoradiation followed by surgery (pre-OP CRT) has been widely applied in the treatment of patients with esophageal cancer, some studies have shown a survival benefit of postoperative chemoradiation (post-OP CRT). The optimal combination of multimodality therapy and the sequence of surgery and chemoradiation for esophageal cancer remain to be investigated.A total of 1385 patients with clinical stage II and III esophageal squamous cell carcinoma (ESCC) were included. On the basis of the sequence of surgery and chemoradiation, the patients were grouped as follows: preoperative chemoradiation followed by surgery (pre-OP CRT+S), surgery alone (S), and surgery followed by postoperative chemoradiation (S+post-OP CRT). Propensity score matching analysis was used to identify 78 well-balanced patients in each group for outcome comparison.In all, 753, 339, and 293 patients were in the pre-OP CRT+S, S, and S+post-OP CRT groups, respectively. Before matching, no differences were observed in the overall survival among the patients in these 3 groups (P = 0.422). After matching, both the pre-OP CRT+S and S+post-OP CRT groups were significantly associated with a better survival compared with the S group (pre-OP CRT+S vs. S: P < 0.001; S+post-OP CRT vs. S: P = 0.005). In contrast, the survival was similar between the pre-OP CRT+S and S+post-OP CRT groups (P = 0.544). In the subgroup analysis, patients with clinical T3/4 stage tumors or those with a tumor size greater than 5 cm were more likely to demonstrate an overall survival benefit from pre-OP CRT compared with post-OP CRT.Both pre-OP CRT and post-OP CRT demonstrated a survival benefit compared with surgery alone, which indicates the importance of trimodality therapy in patients with clinical stage II/III ESCC. However, no survival difference was observed among patients in the pre-OP CRT+S and S+post-OP CRT groups, which suggests that the sequence of surgery and chemoradiation may be irrelevant to the outcome.

Recently Updated Preliminary Results of an On-Going Phase 1/2 Trial Using Trimodality Therapy in Patients With Postprostatectomy High-Risk Pathologic (p) T2-3N0M0 Prostate Cancer

Recently Updated Preliminary Results of an On-Going Phase 1/2 Trial Using Trimodality Therapy in Patients With Postprostatectomy High-Risk Pathologic (p) T2-3N0M0 Prostate Cancer

Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-up

Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-up

Preliminary updated results of a phase I/II trial using trimodality therapy in patients with post-prostatectomy high-risk pathologic (p) T2-3N0M0 prostate cancer.

e16084 Background: We present the updated preliminary results of an on-going phase I / II trial with the purpose of determining the safety, feasibility and efficacy of post-prostatectomy 3-D confor...

Incidence of Brain Metastases after Trimodality Therapy in Patients with Esophageal or Gastroesophageal Cancer: Implications for Screening and Surveillance

Background: It is unclear whether patients undergoing trimodality therapy (TMT) should be screened or surveyed for brain metastases. Methods: We retrospectively analyzed esophageal cancer (EC) patients who underwent TMT between the years 2000 and 2010. All were systematically staged and surveyed but none had screening or surveillance brain imaging. Results: The median follow-up time for 518 patients was 29.3 months (range 1-149.2); all patients had adenocarcinoma of the esophagus. Of 188 (36.3%) patients who developed distant metastases, 20 (10.6% of 188 patients or 3.9% of 518 patients) had brain metastases. A higher baseline clinical stage (stage III or IVa) was associated with brain metastases. Most (90%) patients with brain metastases were diagnosed within 24 months of surgery. Sixteen patients had central nervous system symptoms at diagnosis. Twelve (60%) patients had solitary metastasis and 8 (40%) patients had multiple metastases. Although 17 patients received therapy for brain metastases, the median overall survival time of 20 patients was only 10.5 months (95% CI 6.6-14.0). Conclusion: After TMT, 3.9% of EC patients developed brain metastases and their prognosis was poor. Our data suggest that screening and/or surveillance for brain metastases in the EC population undergoing TMT is not warranted.

Complete pathological response is predictive for clinical outcome after tri-modality therapy for carcinomas of the superior pulmonary sulcus

The objective was to define the relationship between histopathological changes after pre-operative chemo-radiotherapy (CRT) and clinical outcome following tri-modality therapy in patients with superior sulcus tumours. A retrospective analysis of tumour material was performed in a series of 46 patients who received tri-modality therapy between 1997 and 2007. Median follow-up was 34 months (5-154). Pathological complete response (pCR) was present in 20/46 tumours (43%). The most common RECIST score after CRT in patients with pCR was a partial response (PR; 10/17, three unknown), whereas in patients without a pCR, stable disease was the most common (22/26) (p = 0.002). In 26 specimens with residual tumour, this was mainly located in the periphery of the lesion rather than the centre (Spearman's correlation = 0.67, p < 0.001). Prognosis was significantly better after a pCR compared to residual tumour (70% 5-year overall survival vs. 20%; p = 0.001) and in patients with fewer than 10% vital tumour cells as compared to those with >10% (65% 5-year overall survival vs. 18%; p < 0.001). A low mitotic count was associated with a longer disease-free survival (p = 0.02). Complete pathological response and the presence of fewer than 10% vital tumour cells after pre-operative CRT are both associated with a more favourable prognosis. A modification of the pathological staging system after radiotherapy, incorporating the percentage of vital tumour cells, is proposed.

Safety and efficacy of trimodality therapy in patients undergoing extrapleural pneumonectomy.

Malignant pleural mesothelioma (MPM) is a rare but rapidly deadly disease (1). Macroscopic complete resection (MCR) is the goal of surgery (2). MCR seems to have the most significant impact on survival in patients undergoing multimodality treatment for MPM. The role of surgical resection in the management of MPM remains controversial.