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We evaluated whether the amount of circulating DNA in plasma could discriminate between lung cancer patients and healthy individuals and whether it is related to disease progression, and we analyzed the kinetics of plasma DNA in disease-free, surgically resected patients. Plasma DNA quantification and analysis of microsatellite alterations were performed in a consecutive series of 84 patients with non-small cell lung cancer, who were studied during follow-up, and 43 healthy controls. In patients, the mean values of plasma DNA concentration were higher than in controls even considering stage Ia patients. Sensitivity and specificity estimates were calculated as the area under the receiver operating characteristic curve (AUC-ROC) curve and showed a value of 0.844. Variations in DNA level and in microsatellite changes correlated with the clinical status of 38 patients monitored during follow-up. The data suggest that quantification and molecular characterization of plasma DNA in lung cancer patients are valuable noninvasive diagnostic tools for discriminating patients from unaffected individuals and for detecting early recurrence during follow-up.

Background This study aimed to review the activity of cytotoxic chemotherapy in patients with inflammatory myofibroblastic tumors (IMTs) treated at nine European sarcoma reference centers. Materials and Methods Patients of any age, with histologically proven IMT, treated with anthracycline-based methotrexate plus/minus vinorelbine/vinblastine (MTX-V) or other chemotherapeutic regimens between 1996 and 2018 were retrospectively reviewed. Diagnosis was confirmed at the local level by an expert pathologist. Response was retrospectively assessed by local investigators by RECIST v1.1. Progression-free survival (PFS), relapse-free survival (RFS), and overall survival (OS) were computed by Kaplan-Meier method. Results Thirty-eight patients were included. Twenty-five patients (8 localized, 17 advanced disease) received an anthracycline-based regimen; 21 were evaluable for response. Overall response rate (ORR) was 10/21 (47.6%). At a 70.8-month median follow-up (FU), median RFS and median OS were not reached (NR) in patients with localized disease; median PFS and median OS were 6.3 (interquartile range [IQR]: 1.9–13.4) and 21.2 (IQR: 7.7–40.7) months in patients with advanced disease. Thirteen patients received MTX-V (4 localized, 9 advanced disease), all evaluable for response. ORR was 7/13 (53.8%). At a 56.6-month median FU, median RFS and median OS were 42.5 (IQR: 12.9–61.2) months and NR (no death events) in patients with localized disease, and NR (IQR: 24.9 to NR) and 83.4 months (IQR: 83.4 to NR) in patients with advanced disease. In the “other-regimens group,” responses were seen in 3/4 patients treated with oral cyclophosphamide and 1/2 with docetaxel/gemcitabine. Conclusion Anthracycline-based and MTX-V regimens are very effective in IMT, with a similar ORR in both groups. MTX-V achieved a prolonged disease control. Responses were also seen with oral cyclophosphamide and docetaxel/gemcitabine, but few patients were treated with these schedules. Implications for Practice Inflammatory myofibroblastic tumor (IMT) is an ultrarare sarcoma with known sensitivity to anaplastic lymphoma kinase (ALK) inhibitors in ALK-fused cases, although ALK inhibitors are not licensed in the disease. The current knowledge on the activity of cytotoxic chemotherapy is limited. This multi-institutional retrospective study on pediatric and adult patients with IMT shows that cytotoxic chemotherapy, and in particular anthracycline-based and methotrexate plus/minus vinorelbine/vinblastine regimens, represents a treatment option and can be considered in IMT patients irrespectively from ALK status. This study provides a benchmark for future studies on new medical therapies.

We evaluated the impact of the number of cycles of platinum based, first line chemotherapy (fewer than 6 cycles vs the conventional 6 cycles or more) on the survival of patients with metastatic urothelial carcinoma.We used the RISC (Retrospective International Study of Invasive/Advanced Cancer of the Urothelium) database. The association of the number of cycles of chemotherapy with overall survival was investigated by Cox multiple regression analysis after controlling for recognized prognostic factors. We excluded patients who received fewer than 3 or more than 9 platinum chemotherapy cycles to reduce confounding factors. The primary analysis was a comparison of overall survival for 3 to 5 vs 6 to 9 cycles using 6-month landmark analysis when 281 death events were observed.Of the 1,020 patients in the RISC 472 received cisplatin or carboplatin, of whom 338 and 134, respectively, were evaluable. A total of 157 patients received 3 to 5 cycles (median 4) and 315 received 6 to 9 cycles (median 6). There was no significant difference in overall survival between 3 to 5 and 6 to 9 cycles (HR 1.02, 95% CI 0.78-1.33, p = 0.91). No significant interactions were observed for the type of platinum (p = 0.09) and completed planned chemotherapy (p = 0.56). The limitations of a hypothesis generating, retrospective analysis applied.Four cycles of platinum based, first line chemotherapy appeared adequate and did not significantly compromise the survival of patients with advanced urothelial carcinoma. The omission of excessive cycles may avoid unnecessary cumulative toxicity and facilitate a better transition to second line therapy and investigational switch maintenance therapy strategies. These results require prospective validation but they may impact practice in select patients.

Contains fulltext : 220839.pdf (Publisher’s version ) (Closed access) BACKGROUND: Intimal sarcoma (InS) is an exceedingly rare neoplasm with an unfavorable prognosis, for which new potentially active treatments are under development. We report on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in patients with InS. METHODS: Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis. Patients with MDM2-positive InS who were treated with anthracycline-based regimens, gemcitabine-based regimens, or pazopanib between October 2001 and January 2018 were selected. Local pathological review was performed to confirm diagnosis. Response was assessed by RECIST1.1. Recurrence-free survival (RFS), progression-free survival (PFS) and overall survival were computed by Kaplan-Meier method. RESULTS: Seventy-two patients were included (66 anthracycline-based regimens; 26 gemcitabine-based regimens; 12 pazopanib). In the anthracycline-based group, 24 (36%) patients were treated for localized disease, and 42 (64%) patients were treated for advanced disease. The real-world overall response rate (rwORR) was 38%. For patients with localized disease, the median RFS was 14.6 months. For patients with advanced disease, the median PFS was 7.7 months. No anthracycline-related cardiac toxicity was reported in patients with cardiac InS (n = 26). For gemcitabine and pazopanib, the rwORR was 8%, and the median PFS was 3.2 and 3.7 months, respectively. CONCLUSION: This retrospective series shows the activity of anthracycline-based regimens in InS. Of note, anthracyclines were used in patients with cardiac InS with no significant cardiac toxicity. The prognosis in patients with InS remains poor, and new active drugs and treatment strategies are needed.

Aim During the last years, the role of sentinel lymph node mapping (SLNM) for endometrial cancer (EC) surgical treatment has increased in popularity. However, several controversies remain about different technical steps of SLNM. Thus, a randomised control trial was designed to compare cervical (CI) and hysteroscopic (HI) indocyanine green (ICG) injection for SLNM of newly diagnosed EC undergoing surgical staging. The primary end-point of the study was to compare these two techniques in terms of para-aortic detection rate. Methods Patients with apparent stage I or II histologically confirmed EC undergoing surgery were included in the study. This randomised trial distinguished patients in two study groups according to two different techniques of ICG SLNM: CI versus HI injection. Patients who met the inclusion criteria were randomly assigned to CI or HI injection in a 1:1 ratio. The central randomisation system allocated patient randomisation numbers sequentially in the order in which the patients were enrolled. This randomised trial was not blinded for either patients or the surgeons. Results From March 2017 until April 2019, a total of 165 patients were randomised in this study: 85 (51.5%) in the CI group and 80 (48.5%) in the HI group. After randomisation, 14 (8.5%) patients were excluded from the study. Finally, 151 patients were included in the analysis: 82 (54.3%) in the CI group and 69 (45.7%) in the HI group. Hysteroscopy injection shows an ability to detect Sentinel nodes (SNLs) in the para-aortic area of about 10% greater compared with CI injection, although this difference did not reach statistical significance. The HI technique was superior in detecting isolated para-aortic SLNs (5.8% Versus 0%). The CI injection was correlated with higher SLN detection rates at the pelvic level compared with HI injection. Pelvic and overall detection was higher in the CI group. Conclusions The present study supports the adoption of CI instead of HI injection because the former allows better identification of sentinel nodes (especially in the pelvic area). Detection of SLN in the para-aortic area was slightly higher in patients receiving a HI injection, but the difference with the CI route was not statistically significant.

OBJECTIVE To evaluate the prognostic impact of lymph node yield (LNY) on survival outcomes for penile squamous cell carcinoma (SCC). PATIENTS AND METHODS In all, 532 patients who underwent inguinal LN dissection (ILND) across tertiary referral centres from Europe, China, Brazil and North America were retrospectively evaluated. From this cohort, 198 patients received pelvic LND (PLND).We identified threshold values for ILND and PLND using receiver operating characteristic curves. We tested prognostic value of LNY for recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) using the Kaplan-Meir method and Cox proportional hazard regression models. RESULTS The median (interquartile [IQR]) age was 59 (49-68) years and the median (IQR) follow-up after ILND was 28 (12-68.2) months. Overall, 85% of the patients had bilateral dissections. The median (IQR) number of inguinal LNs removed was 15 (10-22). Of those receiving PLND, The median (IQR) number of LNs was 13 (8-19). A LNY of ≥15 was used for dichotomisation of ILND patients, and a LNY of ≥9 was used in the PLND cohort. Patients with a LNY ≥15 had significantly better 5-year OS vs patients with a LNY

In a retrospective analysis of data from 13 European Society for Blood and Marrow Transplantation (EBMT) centers, we evaluated the contemporary outcomes of high-dose chemotherapy (HDCT) as salvage therapy of advanced seminoma. The results supported the use of HDCT, particularly for patients with chemosensitive disease. This proof of concept needs to be prospectively validated in a randomized trial of HDCT versus standard-dose chemotherapy. Background: The optimal management of advanced seminoma that relapses after chemotherapy remains unknown. We retrospectively analyzed outcomes with the use of high-dose chemotherapy (HDCT). Patients and Methods: Eligibility included adult male patients with pure seminomatous histology and treatment with salvage HDCT. Data of patients who received HDCT from 13 European Society for Blood and Marrow Transplantation (EBMT) centers were used. Multivariable Cox analyses evaluated the association of prespecified factors (line of treatment, prior radiotherapy, and chemosensitivity according to standard definition), with progression-free (PFS) and overall survival (OS). The prognostic ability of the model was assessed through the concordance statistic. Results: From December 2002 to December 2012, 46 cases were identified. Median age was 38 years (interquartile range, 35-46 years). HDCT was provided as second-line therapy (n = 14, 30.4%) and in third-line or beyond third-line therapy (n = 20, 43.5%; 12 had missing information). Sixteen patients (34.8%) received paraortic and/or iliac radiotherapy, and 10 (21.7%) had disease that was cisplatin refractory or absolutely refractory. Median follow-up was 22 months (interquartile range, 8-56). On multivariable Cox analysis, refractory disease was a significantly negative prognostic factor for both PFS (hazard ratio, 6.04; 95% confidence interval, 1.86-19.64) and OS (hazard ratio, 3.93; 95% confidence interval, 1.07-14.45), while prior radiotherapy trended to significance for both. The c index was 0.74 and 0.66 for PFS and OS, respectively. The small numbers and the lack of any comparison with conventional-dose chemotherapy are major study limitations. Conclusion: Despite our small sample size, this retrospective analysis suggested that HDCT may represent a valuable therapeutic option for patients with a pure seminoma after standard-dose chemotherapy failure. Our observation requires validation through a prospective study.

The administration of adjuvant chemotherapy for patients with penile squamous cell carcinoma (PSCC) with high-risk features is controversial. In 21 patients who had received adjuvant taxane, cisplatin, and 5-fluorouracil, the expression of p53 in the tumor-positive lymph nodes was the only factor that showed a trend toward poorer survival endpoints. If confirmed, these findings could help in selecting the best candidates for adjuvant chemotherapy. Background: Little is known about the outcomes and prognostic factors of adjuvant chemotherapy for locally advanced penile squamous cell carcinoma after regional lymphadenectomy (LAD). Patients and Methods: We retrospectively reviewed the data from 21 patients who had received taxane, cisplatin, and 5-fluorouracil (TPF, every 3 weeks) in the adjuvant setting at our center. Univariable and multivariable Cox regression analyses were undertaken for disease-free (DFS) and overall survival (OS) of TPF. Results: The patients had received TPF from July 2004 to July 2012 after inguinal (n = 6) or inguinal plus pelvic LAD (n = 15), and the median follow-up was 52 months. Thirteen (61.9%) had pelvic and 5 (23.8%) bilateral inguinal nodal metastases. The median time from LAD to the start of TPF was 5.4 weeks (interquartile range [IQR], 4.1-7.3 weeks). Metastatic tumor tissue from 11 of 19 evaluable patients (57.9%) showed positive immunohistochemistry staining for p53. Univariably, only the expression of p53 showed a trend toward poorer DFS (hazard ratio [HR], 4.14; 95% confidence interval [CI], 0.87-19.68; P = .074) and OS (HR, 4.54; 95% CI, 0.95-21.56; P = .056). The same results were obtained multivariably for DFS (HR, 3.76; 95% CI, 0.78-17.96; P = .096) and OS (HR, 4.29; 95% CI, 0.89-20.57; P = .067). The median DFS was 8.9 months (IQR, 5.9-22.7 months) for p53-expressing patients versus not estimable for non p53-expressing patients (P = .051) and the median OS was 17.2 months (IQR, 12.8-22.7 months) and not estimable, respectively (P = .037). Conclusion: In patients who had received adjuvant TPF for node-positive penile squamous cell carcinoma, p53 IHC expression seemed to be associated with a poorer outcome, and further study is warranted in larger data sets to confirm these findings. This information might be useful to improve the prognostic allocation. (C) 2016 Elsevier Inc. All rights reserved.

Panitumumab showed clinical activity in patients with penile squamous cell carcinoma from a single center. The targeting of the epidermal growth factor receptor will deserve investigation in combination with chemotherapy and in earlier stages. New insights into the biology of disease and into the current role of standard chemotherapy are required to better select the optimal candidates for treatment. Background: Patients with metastatic penile squamous cell carcinoma (SCC) have a poor prognosis and treatment options are needed when chemotherapy treatment fails. We present the final results of panitumumab treatment from our original series. Patients and Methods: Eligibility included patients with unresectable or metastatic penile SCC, Eastern Cooperative Oncology Group performance status of 0 to 2, and failure of at least 1 chemotherapy regimen. Patients received panitumumab 6.0 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Response was assessed by clinical examination or Response Evaluation Criteria in Solid Tumors version 1.1 criteria every 6 weeks, when applicable. Descriptive statistics were calculated and univariable Cox proportional hazards regression analysis was conducted. Results: Between October 2010 and July 2013, 11 patients were treated. After a median of 5 panitumumab administrations (range, 1-11), we recorded 1 case of Grade 3 cutaneous toxicity and diarrhea each, and 2 cases of Grade 3 mucositis. One patient discontinued treatment because of skin toxicity. Two patients had a complete remission of skin nodules and of skin and nodal metastases, respectively. One patient had a partial regression of skin metastases, and 2 patients stable disease (clinical benefit: 45.5%). Median progression-free survival was 1.9 months (interquartile range [IQR], 0.9-3.0 months) and median overall survival (OS) was 9.5 months (IQR, 4.9-12.6). The presence of visceral metastases showed a trend for association with worse OS (P = .098). Conclusion: Panitumumab was active and safe in patients with highly pretreated penile SCC. The design of combination or sequential strategies with chemotherapy and in an earlier disease stage is warranted. (C) 2015 Elsevier Inc. All rights reserved.

Background: Limited data is available on the role, and extent of, postchemotherapy lymphadenectomy (PC-LND) in patients with clinical evidence of pelvic (cN1-3) or retroperitoneal (RP) lymph node spread from urothelial bladder carcinoma. Objective: To compare the outcomes of operated versus nonoperated patients after first-line chemotherapy. Design, setting, and participants: Data from 34 centers was collected, totaling 522 patients, treated between January 2000 and June 2015. Criteria for patient selection were the following: bladder primary tumor, lymph node metastases (pelvic. ±. RP) only, first-line platinum-based chemotherapy given. Intervention: LND (with cystectomy) versus observation after first-line chemotherapy for metastatic urothelial bladder carcinoma. Outcome measures and statistical analysis: Overall survival (OS) was the primary endpoint. Multiple propensity score techniques were adopted, including 1:1 propensity score matching and inverse probability of treatment weighting. Additionally, the inverse probability of treatment weighting analysis was performed with the inclusion of the covariates, that is, with doubly robust estimation. Results and limitations: Overall, 242 (46.4%) patients received PC-LND and 280 (53.6%) observation after chemotherapy. There were 177 (33.9%) and 345 (66.1%) patients with either RP or pelvic LND only, respectively. Doubly robust estimation-adjusted comparison was not significant for improved OS for PC-LND (hazard ratio [HR]: 0.86, 95% confidence interval [CI]: 0.56-1.31, p = 0.479), confirmed by matched analysis (HR: 0.91, 95% CI: 0.60-1.36, p = 0.628). This was also observed in the RP subgroup (HR: 1.12, 95% CI: 0.68-1.84). The retrospective nature of the data and the heterogeneous patient population were the major limitations. Conclusions: Although there were substantial differences between the two groups, after accounting for major confounders we report a nonsignificant OS difference with PC-LND compared with observation only. These findings may be hypothesis-generating for future prospective trials. Patient summary: We found no differences in survival by adding postchemotherapy lymphadenectomy in patients with pelvic or retroperitoneal lymph node metastatic bladder cancer. The indication to perform postchemotherapy lymphadenectomy in the most suitable patients requires additional studies. In contemporary cohorts of patients with metastatic pelvic or retroperitoneal lymph nodes from bladder cancer, we found no survival benefit from postchemotherapy surgery versus observation in a retrospective study. Performing postchemotherapy lymphadenectomy remains investigational in patients with metastatic bladder cancer.

FGFR gene alterations represent a target for treatment in clinical trials of urothelial carcinoma (UC). Little is known about their prognostic effect in patients with metastatic UC. We analyzed data for 112 patients treated with platinum-based first-line chemotherapy at our center between October 2011 and March 2017 and who were screened for the presence of FGFR mutations or gene fusions within multiple clinical trials with pan-FGFR inhibitors. Centralized targeted exome sequencing analyses were performed to detect multiple FGFR mutations and fusions. Cox regression analyses were performed, adjusting for recognized prognostic factors. Thirty-seven patients (33%) had upper tract UC (UTUC). A total of 22 patients (19.6%) had FGFR alterations and ten (8.9%) received salvage pan-FGFR inhibitor therapy. Thirty-two patients (45.4%) received salvage treatment with an immune checkpoint inhibitor. FGFR alterations were more frequently observed in UTUC versus bladder UC (p=0.017). On multivariable analyses, FGFR alterations were not significantly associated with OS (p=0.860) or PFS (p=0.147) after first-line chemotherapy. PATIENT SUMMARY: In an original single-center study, FGFR gene alterations were not prognostic for either progression-free survival or overall survival in patients receiving first-line chemotherapy for metastatic urothelial carcinoma. These results will be useful in interpreting findings from future clinical trials.

To improve the prognostic allocation of patients with penile squamous-cell carcinoma (PSCC) receiving regional lymph node dissection (LND).An international, multicenter, retrospective study was performed on patients with PSCC who received regional LND, with or without perioperative therapy, from 1980 to 2017. We first used a random forest (RF) method with missing data imputation. Additionally, data were modeled using Cox proportional hazard regression, and a Cox model was also fit including prespecified variables. Based on the latter model, a nomogram for estimating 12-month and 24-month overall survival (OS) was developed.There were 743 patients who received LND at 7 referral centers from Europe, the USA, Brazil, and China. Of these patients, 689 were analyzed: 86 (12.5%) received neoadjuvant chemotherapy (NAC); 171 (24.8%) received adjuvant chemotherapy (AC), and 74 (10.7%) received adjuvant radiotherapy. The variables significantly associated with OS were age (P0.001), the pathologically involved/total removed LN ratio (P0.001), pN stage (overall P0.001), and NAC (P = 0.013). NAC and AC were ineffective in N1-2 patients (clinical and pathological, respectively), whereas they provided OS improvements in N3 patients. Finally, we developed a nomogram predicting 12- and 24-month OS based on prespecified variables (c-index: 0.75). The study is limited by its retrospective nature.We propose a tool that can be offered as an aid to physicians to enhance decision-making, clinical research, and patient counseling whenever LND is needed for PSCC. Administration of NAC and AC should be restricted to clinical and pathological N3 patients, respectively.

Objective To harness the frontline therapy in advanced penile squamous cell carcinoma (PSCC), for which chemotherapy exerts moderate activity but poor efficacy. Dacomitinib is an irreversible, pan-epidermal growth factor receptor (HER) inhibitor. Patients and Methods In a phase 2 study (NCT01728233), patients received dacomitinib 45 mg/day, orally, continuously. Inclusion criteria were SCC histology, clinical stage N2-3 or M1 (TNM 2009), and no prior chemotherapy administration. The primary endpoint was the objective response-rate (ORR, according to RECIST v1.1). Stopping rules based on the Bayesian posterior probability (PP) to demonstrate that the ORR exceeded 20% were set. Results From June 2013 to October 2016, 28 patients were treated. Eight (28.6%) had visceral metastases, 14 (50%) had pelvic and 17 (60.7%) clinically-involved bilateral lymph nodes. One complete and eight partial responses were obtained (ORR: 32.1%, 80% credibility interval 21.0-43.0%). The median follow-up duration was 19.8 months (IQR: 6.3-25.7); 12-month progression-free survival was 26.2% (95%CI: 13.2-51.9); 12-month overall survival (OS) was 54.9% (95%CI: 36.4-82.8). The median OS of locally-advanced patients was 20 months (IQR: 11.1-not reached). The Bayesian PP of exceeding the 20% ORR target was 92.3%. Grade 3 adverse events (skin rash) were seen in 3 patients (10.7%). Tissue samples from 25 patients were analyzed. Only two patients had HR-HPV-positive tumor. EGFR amplification was found in 4 patients (equally responders and non responders) and it was confirmed in all post-dacomitinib samples. TERT mutations (60%) were found in responders only, PI3K/mTOR pathway gene mutations in 42.9% responders versus 8.3% non responders. Conclusion Dacomitinib was active and well tolerated in patients with advanced PSCC and may represent an option when combination chemotherapy cannot be administered. Mutations in downstream effectors of EGFR signaling in relation to dacomitinib activity deserve further studies. This article is protected by copyright. All rights reserved.

Background Outcomes of neoadjuvant chemotherapy in patients with muscle-invasive urothelial bladder carcinoma (MIUBC) should be improved. Sorafenib was combined with gemcitabine and cisplatin chemotherapy (SGC) in an open-label, single-arm, phase 2 trial (NCT01222676). Patients and methods After transurethral resection of the bladder, T2–T4a N0 patients received four cycles of SGC followed by cystectomy. Sorafenib 400 mg q12h daily, continuously, was added to standard GC chemotherapy. In a Simon's 2-stage design, the primary endpoint was the pathologic complete response (pT0), assuming H0: ≤0.20 and H1: ≥0.40, with a type I and type II error of 5% and 10%, respectively. Results From April 2011 to June 2016, 46 patients were enrolled. Pathologic T0 response was obtained in 20 patients (43.5%, 95% CI: 28.9–58.9); pT ≤ 1 in 25 (54.3%, 95% CI: 39.0–69.1). After a median follow-up of 35 months, the median progression-free survival was not reached (NR, interquartile range: 23.6–NR), nor was median overall survival (interquartile range: 30.3–NR). Hematologic and extrahematologic grade 3 to 4 adverse events occurred in 45.6% and 26.1% of patients, respectively. In 29 samples from responders (pT ≤ 1) and nonresponders, different distribution of missense mutations involved DNA-repair genes, RAS-RAF pathway genes, chromatin-remodeling genes, and HER-family genes. ERCC1 immunohistochemical expression was associated with pT ≤ 1 response ( P = 0.047). The absence of a comparator arm prevented us to quantify sorafenib contribution. Conclusions SGC combination was active in MIUBC, and the identified molecular features included alterations that may help personalize treatment in MIUBC with new more potent targeted agents, combined with chemotherapy.

Background Limited information is available regarding the use of androgen receptor (AR) immunohistochemical expression in muscle-invasive or metastatic urothelial carcinoma. We aimed to evaluate the frequency of AR expression by tumor cells (TC), its prognostic role, and its relationship with programmed cell-death ligand 1 (PD-L1) expression in these patients. Patients and Methods From September 2015 to January 2017, we collected tissue from patients who received platinum-based chemotherapy at our center. Immunohistochemistry for AR was performed (1% cutoff of TC). PD-L1 coexpression, by TC or immune cells (1% cutoff), was also analyzed. Molecular analysis of AR gene was performed by sequencing of exons 5 to 8 and by fluorescence in-situ hybridization analysis. Cox models for overall survival (OS), adjusted for stage, visceral metastases, and platinum type, were fitted. Results A total of 110 patients had tumor samples stained. Overall, 48 (43.6%) had AR-expressing TC: 19 (17.3%) had 1%-5% expression, 15 (13.6%) 5%-25% expression, and 14 (12.7%) > 25% expression. Among the latter, 7 had molecularly evaluated tumor tissue: no AR gene mutations or amplifications were found, but polysomy of Xq chromosome was seen. PD-L1 expression by TC and immunohistochemistry concordantly decreased with increasing levels of AR expression by TC. In Cox analyses, AR expression was not associated with OS, both on univariable ( P = .477) and multivariable ( P = .505) analyses. Conclusion AR is frequently expressed in patients with muscle-invasive and advanced urothelial carcinoma, and it does not seem to be prognostic for OS. The AR pathway is worthy of clinical studies to assess its synergistic action with anti–PD-L1 therapy.

Administration of high-dose chemotherapy with stem cell support in patients 40 years of age or older with advanced germ cell tumours: a retrospective study from the European Society for Blood and Marrow Transplantation database

Background: Therapeutic options for patients with chemoresistant germ cell tumors (GCTs) are limited. Pazopanib is a selective tyrosine kinase inhibitor with distinct antiangiogenic activity. We aimed to evaluate pazopanib activity in patients with refractory GCT. Patients and methods: In the open-label, single-arm, phase 2 Pazotest study (NCT01743482), patient eligibility included failure of >= 2 platinum-based regimens, and allowed prior high-dose chemotherapy administration. Patients were given pazopanib 800 mg/day until disease progression (PD) or onset of unacceptable toxicity. Measurements of serum tumor markers (STM), computed tomography and FDG-PET were carried out at baseline, after 4 weeks of pazopanib treatment, and every 8 weeks thereafter. PD was defined as increasing levels of STM, increasing size of non-teratomatous masses, or appearance of new lesions. The study primary endpoint was progression-free survival (PFS, H0: 3-month PFS = 25%, alpha = 5%, beta = 20%). Results: Forty-three patients were enrolled from May 2013 to July 2016. The number of prior chemotherapy regimens was: 2 (11.6%), 3 (51.2%), >3 (37.2%). Grade 3 adverse events were observed in six patients (13.9%). Overall, 70.3% of patients had reduced levels of STM after 4 weeks. There were 2 partial responses (4.7%), 19 cases of stable disease, and 16 cases of PD (6 not evaluable by RECIST). The median follow-up duration was 29.6 months. The 3-month PFS probability was 12.8% [95% confidence interval (CI): 5.7%-28.9%]. The 24-month OS probability was 14.2% (95% CI: 6.0%-33.7%). In patients with a > 50% decline in STM, the 24-month OS probability was 24.1% (95% CI: 8.3%-69.6%). The small sample size was the major limitation. Conclusions: Despite pazopanib showed potent but short-lived activity in refractory GCT, long-term survival was obtained in a proportion of treated patients. According to the kinetics of pazopanib activity, this drug may be investigated in less pre-treated patients as an optimal bridging therapy preceding and/or combined with salvage chemotherapy.

IF 16.265; International audience; BACKGROUND:The available prognostic models for overall survival (OS) in patients with metastatic urothelial carcinoma (UC) have been derived from clinical trial populations of cisplatin-treated patients.OBJECTIVE:To develop a new model based on real-world patients.DESIGN, SETTING, AND PARTICIPANTS:Individual patient-level data from 29 centers were collected, including metastatic UC and first-line cisplatin- or carboplatin-based chemotherapy administered between January 2006 and January 2011.INTERVENTION:First-line, platinum-based, combination chemotherapy.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The population was randomly split into a development and a validation cohort. Generalized boosted regression modelling was used to screen out irrelevant variables and address multivariable analyses. Two nomograms were built to estimate OS probability, the first based on baseline factors and platinum agent, the second incorporating objective response (OR). The performance of the above nomograms and that of other available models was assessed. We plotted decision curves to evaluate the clinical usefulness of the two nomograms.RESULTS AND LIMITATIONS:A total of 1020 patients were analyzed (development: 687, validation: 333). In a platinum-stratified Cox model, significant variables for OS were performance status (p

Background Progress in developing effective salvage therapies for UC is warranted. Alisertib is an orally available, selective inhibitor of the aurora kinase A. Methods A single-group, phase 2 trial was conducted with alisertib 50 mg orally BID for 7 days, with 14d rest until disease progression (PD) (NCT02109328). The primary endpoint (EP) was RECIST 1.1 objective response-rate (ORR, H-0 a parts per thousand currency sign 5 %, H-1 a parts per thousand yen 20 %, alpha = 10 % and beta = 20 %). Eligibility included failure of at least one platinum-based regimen. Results From 10/2014 to 04/2015, 22 patients were enrolled (20 evaluable for response), 8 (36.4 %) in second-line and 14 (63.6 %) beyond the second-line. Eight (36.4 %) had an ECOG-performance status 1-2. Two partial responses (PR, ORR: 9.1 %), 7 stable disease (SD) and 11 PD were obtained. Median follow-up was 8.3 months (IQR: 7-10.3), 6-month progression-free survival (PFS) was 13.6 % (95%CI: 4.8-39.0). Two SD are still receiving treatment after 11.5 and 6.3 months. Median overall survival (OS) was not reached (6-month OS: 59.1 %, 95%CI: 41.7-83.7). Hb < 10 g/dl was significantly associated with shorter PFS and OS multivariably (p = 0.031 and p = 0.033). Tissue of the case with 11.5 month SD harbored a missense mutation of mTOR (E1813D), the nonsense mutation Q527STOP of TSC1, HER3 and TAF1L missense mutations. Grade 3-4 adverse events (AE) were: 40.9 % mucositis, 36.4 % fatigue, 18.2 % neutropenia (13.6 % febrile neutropenia). There were 2 treatment-related deaths. Conclusions The study did not meet the primary EP, yet sustained disease control was obtained in about 14 % of patients. The incidence of AE and the issue of patient selection are two major concerns.

Purpose: To explore prognostic factors in surgically treated aggressive fibromatosis (extra-abdominal desmoid tumor). Patients and Methods: A total of 203 consecutive patients treated with surgery over a 35-year period at a single referral center were retrospectively reviewed. One hundred twenty-eight were first seen at our institution with primary disease, whereas 75 had a recurrent tumor. All patients underwent macroscopically complete resection. Margins were rated as negative in 146 (97 with primary tumors, 49 with recurrences) and positive in 57 (31 in primary, 26 in recurrences) patients. Median follow-up was 135 months. Results: Patients with primary disease had a better disease-free survival rate than those with recurrence (76% v 59% at 10 years). Presenting with a recurrence was also the strongest predictor of local failure in the multivariate analysis. In patients first treated for primary disease, size and site had prognostic significance, whereas microscopically positive surgical margins did not. In contrast, in patients with recurrence, there was a trend toward better prognosis if margins were negative (although this was not significant at multivariate analysis). Conclusion: Presence of microscopic disease does not necessarily affect long-term disease-free survival in patients with primary presentation of extra-abdominal desmoid tumors. Thus, function-sparing surgery may be a reasonable choice when feasible without leaving macroscopic residual disease. In patients with recurrences, positive margins may more clearly affect prognosis, potentially necessitating adjuvant radiation in selected cases.

Objectives Approximately one-third of the metastatic germ cell tumors (GCT) in patients are classified as intermediate-risk metastatic GCT, and available guidelines recommend the same treatment of poor-risk cases. Yet the prognosis of these patients is heterogeneous, and consequently refining the intensity of treatment is warranted. We aimed to address the heterogeneity of this category by providing a proof of principle for reclassification attempt. Patients and methods Data on consecutive patients with intermediate-risk metastatic GCT and who received treatment at Fondazione INT Milano in the time frame between February 1980 and March 2014 were collected. Cox regression analyses were done, evaluating potential prognostic factors for overall survival (OS, primary end point) to first-line therapy. Each factor was evaluated in a multivariable model. Recursive partitioning was performed to define prognostic risk groups. Results A total of 224 patients were suitable for the present analysis. Median age was 26 years (interquartile range: 22–31), 11 patients (4.9%) had a retroperitoneal primary tumor, 6 yielded seminomatous histology, 85 (37.9%) had lung metastases, and 58 (25.9%) had bulky (i.e.,≥10 cm) retroperitoneal lymph nodes. Patients received cisplatin, bleomycin, and etoposide (PEB, n = 199) or vinblastine (PVB, n = 23); however, 2 patients received other treatments. Median follow-up was 135 months (interquartile range: 81–223). Globally, 5-year progression-free survival and OS rates were 72.8% (95% CI: 67.1–79.0) and 86.2% (81.7–91.0), respectively. In the multivariable model for OS, elevated alfa fetoprotein (AFP) level was the only significant prognostic factor (hazard ratio = 1.48, 95% CI: 1.12–1.96). The 2 separate prognostic groups with differential OS outcomes were identified based on the cutoff level of 6,200 IU/ml. The 10-year OS rate was 55.6% (95% CI: 36.6–84.3), and it was 86.7% (95% CI: 82.0–91.7) for those with AFP levels more than (n = 19, 8.5%) and less than (n = 205, 91.5%) the cutoff, respectively. Conclusions A small fraction of patients with highly elevated AFP levels have an OS approximating the poor prognostic category, whereas most of them are close to good-risk cases. This might have implications to select outlier patients for clinical trials and molecular characterization.

Background The use of home parenteral nutrition (HPN) in incurable cancer patients is extremely varied across different countries and institutions. In order to assess the clinical impact implied, we previously conducted a survey of incurable cancer patients receiving HPN, which shows that survival was markedly affected by Karnofsky performance status (KPS), tumor spread, Glasgow prognostic score (GPS) and tumor site. The aim of this study was to develop a nomogram incorporating the above factors for survival prediction. Patients and methods We gathered a series of 579 patients, all receiving HPN, which was randomly split into a training and a testing sample. Using Cox proportional hazard regression modeling, a nomogram was built in the training sample, in order to estimate median survival or survival probability at 3 and 6 months according to individual patient characteristics. The nomogram performance was then verified in the testing sample. Results In the training sample, median survival was 3.2 (95% CI 3.0–3.7) months. GPS, KPS, tumor site and spread were confirmed to be significant prognostic factors. A significant interaction was also shown between the site and spread while weight loss (WL), adjusted for body mass index, failed to provide any substantial prognostic contribution. In the testing sample, nomogram performance was good in terms of calibration and discreet regarding discrimination. Conclusion With the growing availability of new oncological treatments and their tendency to transform the trajectory of the advanced cancer into a chronic condition characterized by progressive WL and poor nutrients intake, an increasing number of patients are expected to receive HPN. In such a setting, tools for predicting the survival outcome may play a role toward personalized medicine and for investigating novel experimental therapies. Our proposed nomogram is a step forward in this direction but needs to be made stronger in order to definitely have clinical utility.

In this retrospective study, patients with poor-prognosis germ cell tumors (GCT) treated from a single referral center demonstrated high survival estimates that were stable through the years. Indeed, the major clinical implication is that using the available prognostic classification of metastatic GCT cannot allow the recognition of patients with a true chemoresistant disease. Moreover, the prognostic effect of treating patients with disseminated disease in referral centers should be further assessed. Background: Survival estimates with first-line treatment for patients with metastatic poor prognosis germ cell tumors (GCT) are still suboptimal in the literature. We conducted a retrospective study to evaluate the outcome of patients referred to our tertiary cancer center. Patients and Methods: A retrospective analysis was conducted on patients who received at least first-line chemotherapy at our center. Distribution of clinical characteristics was evaluated in the periods < 1997, 1997 to 2001, 2001 to 2006, and 2007 to 2013. The Kaplan-Meier method was used to estimate progression-free (PFS) and overall survival (OS). Univariable and multivariable Cox models with prespecified clinical variables were undertaken for PFS and OS. All tests and confidence intervals were 2-sided and set at a P = .05 level of significance. Results: Between 1982 and 2013, 168 patients were identified. The median age was 27 years (inter-quartile range [IQR], 22-34). The presence of liver, bone, or brain metastases trended to greater incidence from 1997 onward (27.5% < 1997 to 55.6% in 2007-2013; chi(2) P = .054). Median follow-up was 102 (IQR, 63-166) months. Global 5-year PFS was 48.5% (95% confidence interval [CI], 41.5-56.8) and OS was 63.2% (95% CI, 56.0-71.2). In multivariable analysis, treatment period was not significantly associated with either PFS (overall P = .229) or OS (overall P = .216). Conclusion: In this single-center series of consecutive poor prognosis GCT we could observe greater PFS and OS than the historical estimates. This observation was independent from the period of treatment. Based on the present results, studies focused on improving the outcome in the sole poor-risk cohort should be discouraged. Results were biased by their retrospective quality.

Background In the late 1990s, the use of high-dose chemotherapy (HDCT) and stem-cell rescue held promise for patients with advanced and poor prognosis germ-cell tumors (GCT). We started a randomized phase II trial to assess the efficacy of sequential HDCT compared with cisplatin, etoposide, and bleomycin (PEB). Patients and methods Patients were randomly assigned to receive four cycles of PEB every 3 weeks or two cycles of PEB followed by a high-dose sequence (HDS) comprising HD-cyclophosphamide (7.0 g/m2), 2 courses of cisplatin and HD-etoposide (2.4 g/m2) with stem-cell support, and a single course of HD-carboplatin [area under the curve (AUC) 27 mg/ml × min] with autologous stem-cell transplant. Postchemotherapy surgery was planned on responding residual disease in both arms. The primary end point was progression-free survival (PFS). The study was designed to detect a 30% improvement of 5-year PFS (from 40% to 70%), with 80% power and two-sided α at 5%. Results From December 1996 to March 2007, 85 patients were randomized: 43 in PEB and 42 in HDS arm. Median follow-up was 114.2 months [interquartile range (IQR): 87.7–165.8]. Complete or partial response with normal markers (PRm-) were obtained in 28 (65.1%) and 29 (69.1%) patients, respectively. Five-year PFS was 55.8% [95% confidence interval (CI) 42.8–72.8] and 54.8% (95% CI 41.6%–72.1%) in PEB and HDS arm, respectively (log-rank test P = 0.726). Five-year overall survival was 62.8% (95% CI 49.9–79.0) and 59.3% (95% CI 46.1–76.3). One toxic death (PEB arm) was recorded. Conclusions The study failed to meet the primary end point. Furthermore, survival estimates of conventional-dose chemotherapy higher than expected should be accounted for and will likely limit further improvements in the first-line setting. ClinicalTrials.gov NCT02161692.

Background: To report on a prospective, investigator-driven, phase II study on lapatinib in epidermal growth factor receptor (EGFR)-positive advanced chordoma patients. Patients and methods: From December 2009 to January 2012, 18 advanced progressing chordoma patients entered this study (median age: 61 years; disease extent: metastatic 72% and locally advanced 28%). Epidermal growth factor receptor (EGFR) expression and activation were evaluated by immunohistochemistry and/or phosphoarrays, real-time polimerase chain reaction, fluorescence immunostaining. Fluorescence in situ hybridization analysis was also carried out. Patients received lapatinib 1500 mg/day (mean dose intensity = 1282 mg/day), until progression or toxicity. The primary study end point was response rate (RR) as per Choi criteria. Secondary end points were RR by Response Evaluation Criteria in Solid Tumor (RECIST), overall survival, progression-free survival (PFS) and clinical benefit rate (CBR; RECIST complete response + partial response (PR) + stable disease (SD) = 6 months). Results: All patients were evaluable for response. Six (33.3%) patients had PR and 7 (38.9%) SD, as their best Choi responses, corresponding to RECIST SD in all cases. Median PFS by Choi was 6 [interquartile (IQ) range 3-8] months. Median PFS by RECIST was 8 (IQ range 4-12) months, with a 22% CBR. Conclusions: This phase II study showed a modest antitumor activity of lapatinib in chordoma. The clinical exploitation of EGFR targeting in chordoma needs to be further investigated, both clinically and preclinically. Clinical trial Registration No: EU Clinical Trials Register trial no. 2009-014456-29. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

A low but invariable proportion of patients with advanced germ cell tumors still fail to be cured by first-line chemotherapy, and the number of life years lost is one of the highest among solid tumors. For patients with chemoresistant disease, the readministration of cisplatin, combined with paclitaxel and gemcitabine (TPG), was tolerable and provided long-term remissions in otherwise incurable patients. Background: Rescue of patients who fail to be cured after 2 or 3 chemotherapy combinations (including high-dose chemotherapy [HDCT]) or whose disease is refractory to cisplatin is still an unmet need. We assessed the efficacy of a triple-combination chemotherapy in the salvage setting, beyond second-line regimens. Patients and Methods: We retrospectively reviewed institutional data on consecutive patients who received paclitaxel 80 mg/m(2) intravenously (IV), cisplatin 50 mg/m(2) IV, and gemcitabine 800 mg/m(2) IV on days 1 and 8 every 3 weeks for a maximum of 8 administrations, followed by surgery. Response, survival (progression-free survival [PFS] and overall survival [OS]), and safety/toxicity outcomes were the end points. The Kaplan-Meier method was used for survival estimates, and multiple Cox regression models were used to analyze the prognostic factors. Results: Seventy-five patients were treated from April 1999 to July 2011. Eight complete responses (CR, 10.7%), 29 partial responses with normal markers (PRm(-), 38.7%), and 13 cases of incomplete response/stable disease were recorded, for a major response rate (CR + PRm(-)) of 49%. Thirty-three patients (44%) underwent surgery, which was radical in 14 cases (42.4%). Two-year PFS was 14.8% (95% confidence interval [CI], 8.5%-25.8%), whereas 2-year OS was 29.5% (95% CI, 20.3%-42.7%). Five-year OS in disease-free patients (no evidence of disease) was 60.3% (95% CI, 42.2%-86.2%), and median OS between patients with and without evidence of disease was significantly different (71 [interquartile range {IQR}, 14-116] vs. 12.5 [IQR, 8-19] months with a 6-month landmark analysis; P=.0019). Conclusion: TPG is an effective combination, and best results were achieved if a radical clearance of residual disease could be accomplished. A randomized comparison with dose-intensified regimens is advisable. (C) 2014 Elsevier Inc. All rights reserved.

Chordoma is a rare tumor, and its natural history is still not well known. All patients affected by localized chordoma surgically treated at Istituto Ortopedico Rizzoli, Bologna, and Istituto Nazionale Tumori, Milan, Italy, between 1980 and 2008 were reviewed. Local recurrence, distant metastasis, and overall survival (OS) were analyzed both from time of diagnosis and from time of local recurrence/distant metastasis. A multivariable analysis to identify independent prognostic factors was carried out. A total of 138 consecutive patients were identified (sacrum 78%, lumbar spine 15%, cervical-dorsal spine 7%). Of these, 130 underwent surgical resection. Median follow-up was 142 months. The 5- and 10-year OS, local relapse-free survival (LRFS), and distant relapse-free survival (DRFS) were, respectively, 78% and 54%, 52% and 33%, and 86% and 72%. Size was an independent prognostic factor for OS (P value

Objective To evaluate the outcome of peniscopically controlled laser excision of early-stage penile carcinoma. Methods Patients treated from 1982 to 2006 were investigated. The primary treatment was excisional surgery alone for in situ or initially invasive flat tumors, and reductive chemotherapy followed by surgery for the exophytic lesions. All excisional procedures were conducted by CO 2 laser under peniscopic control. Results Of a total of 224 patients, 111 underwent partial excision of the glans and/or coronal sulcus surface, and 113 total surface excision. Forty patients underwent reductive chemotherapy. Complete excision was obtained in 221 cases (98.7%) at lateral margins and in 217 cases (96.9%) at deep margin. Postoperative complications were negligible. Overall, the 10-yr recurrence rate was 17.5% (95% confidence interval, 16.4–18.6%), and apparently was not affected by the in situ or invasive nature of the lesion. Amputation was required in nine patients, for a 10-yr amputation rate of 5.5% (range, 5.2–5.7%). In the remaining cases, organ form and curvature were preserved, with satisfactory cosmetic and functional results. Conclusions Early-stage penile carcinomas can be effectively treated with the organ-sparing strategy described here. Because local recurrences occur in a minority of patients and can be safely treated, organ preservation is compatible with local disease control. Reductive systemic chemotherapy in selected exophytic cases broadens the indication for our conservative approach.

We conducted an analysis of immunohistochemical expression of multiple biomarkers in patients with metastatic (M) urothelial carcinoma (UC), including their prognostic effect in the setting of first-line chemotherapy. Expression of vascular endothelial growth factor receptor (VEGFR)-3 and platelet-derived growth factor receptor (PDGFR)-alpha were associated with a divergent prognostic meaning. Present data do not support the use of immunohistochemistry (IHC) to select patients for clinical trials and highlight the hurdles of targeting angiogenesis in this field. Background: Knowledge of the expression of molecular drivers and potentially druggable targets might enhance prognostic classification of M UC. Materials and Methods: We analyzed archival tissue from patients with UC who underwent first-line chemotherapy for locally advanced (LA) and M disease between the years 2000 and 2013. The following biomarkers were evaluated using IHC: excision repair cross complementation (ERCC) group 1 (ERCC1), epidermal growth factor receptor (EGFR), HER2, VEGFR-3, PDGFR alpha, p53, and p63. Expression of ERCC1, EGFR, and HER2 was dichotomized as positive (2+, 3+) or negative (

BACKGROUND The objective of this study was to assess long-term prognosis and patterns of failure in patients with retroperitoneal soft tissue sarcoma who underwent surgery with curative intent at a single institution. Several series of patients with retroperitoneal sarcoma were reported, providing widely variable data regarding local and distant failure. METHODS Overall, 167 consecutive patients who underwent surgery for retroperitoneal soft tissue sarcoma over a 20 year span at a single referral center were reviewed retrospectively. Eighty-two patients presented with primary disease, whereas 85 patients had recurrent locoregional tumors. Surgical resection was considered macroscopically complete in 147 of 167 patients (88%). RESULTS Overall survival at 10 years after definitive surgery was approximately 27%, and the disease-free survival was approximately 16%. Only a minority of patients developed distant metastases. The risk of recurrence was correlated with whether patients underwent surgery for primary disease or for recurrent disease; the 10 year disease-free survival rate was 27% in the former group and 4.6% in the latter group. Histotype and malignancy grade were other prognostic factors, with the former found to be predictive of the pattern of failure and the latter predictive of overall survival. CONCLUSIONS Local recurrence after primary surgery and high-grade malignancy were associated with the worst survival. Histologic subtype appeared to influence the pattern of recurrence, which mainly was local for patients with liposarcoma but was both local and distant for patients with the other histotypes. Cancer 2004. © 2004 American Cancer Society.

There is no clear indication for postchemotherapy surgery in patients with metastatic urothelial cancer (UC). We analyzed the contribution of postchemotherapy lymphadenectomy on survival in patients treated at our center. Twenty-eight patients were identified and results compared with those of a nonsurgically treated cohort. Surgery and response to chemotherapy were prognostic for progression-free (PFS) and overall survival (OS). If confirmed, results might have implications in daily practice and clinical trials. Background: The contribution of postchemotherapy pelvic (PLND) or retroperitoneal lymphadenectomy (RPLND) on survival in patients with advanced and metastatic UC is still unclear. Patients and Methods: Between September 1986 and May 2012, 157 patients with locally advanced or metastatic UC received first-line chemotherapy consisting of mMVAC (modified methotrexate, vinblastine, doxorubicin, and cisplatin), according to our policy. Patients with subdiaphragmatic nodal disease and/or local recurrence only and who experienced at least stable disease (SD) were selected. Fifty-nine patients were identified, 28 of whom underwent surgery, 31 started consolidation chemotherapy with or without radiotherapy or observation. The prognostic effect of candidate factors on survival was evaluated using Cox proportional hazard regression models. Results: A total of 14 PLND and 14 RPLND patients were identified after they had achieved a complete response (CR; n = 7) or a partial response (PR) and SD (n = 21). Median follow-up was 88 months (interquartile range, 24-211 months). Median PFS was 18 (95% confidence interval [CI], 11-not estimated) and 11 (95% CI, 5-19) months, respectively, in favor of the surgical cohort and curves were statistically different (log-rank test, P = .009). In multivariate analysis, postchemotherapy surgery was significantly prognostic for PFS and OS and response to chemotherapy (PR and SD vs. CR) was prognostic for PFS and trended to significance for OS. A model including these 2 factors showed bootstrap-corrected Harrel C statistics for PFS and OS of 0.65 and 0.68, respectively. Conclusion: In well selected patients with UC like those who achieved a clinical benefit with chemotherapy and had nodal metastatic disease, there was a survival advantage in removal of disease residuals.

Primary mediastinal nonseminomatous germ cell tumors comprise a heterogeneous series of neoplasms characterized by limited chemosensitivity and a poor prognosis. We analyzed a large series of patients from our tertiary cancer center, including pre- and postsurgical variables, with the aim to provide a prognostic model that might be suitable for clinical use. The variables identified in the prognostic model were surgical removal of residuals after first-line chemotherapy, histological response, and the presence of lung metastases. Their joint analysis defined distinct overall survival (OS) curves. Background: Primary mediastinal germ cell tumors (PMGCTs) poorly benefit from chemotherapy and half of patients die because of disease progression. Enhancing the risk stratification might result in tailoring a more personalized treatment strategy from the time of diagnosis. Patients and Methods: Between the years 1985 and 2012, 86 patients with PMGCT were treated at our center. Cox proportional hazards regression analysis was conducted in the population of nonseminomas to examine the prognostic effect of candidate factors on progression-free and OS. OS curves were compared using the Kaplan-Meier method and the log-rank test. Results: Mean age was 29.8 years (range, 15-63 years). Twenty-five patients (29.1%) had lung and 8 (9.3%) liver, bone, or brain metastases. Twelve patients (13.9%) received upfront high-dose chemotherapy and 45 patients (52.3%) underwent surgery after chemotherapy. Cox analyses included 61 evaluable primary mediastinal nonseminomatous germ cell tumors (PMNSGCTs). The final model of factors indicating a poor prognosis included the combination of surgery and histological response (overall P = .011) and lung metastases (hazard ratio, 3.03; 95% confidence interval, 1.12-8.15; P = .028). The model showed a bootstrap-corrected Harrel c-statistic for OS of 0.66. A risk stratification model based on the combination of these factors and accounting for a 50% 5-year survival cutoff identified 2 groups (poor prognosis, n = 33 vs. good prognosis, n = 28) with distinct OS curves (P < .001). Preoperative serum tumor marker level was not associated with the final histology (P = .853, chi(2) test). Results were limited by small numbers. Conclusion: Patients with PMNSGCT included 2 subpopulations with distinct prognosis, and therapeutic improvements are needed for patients with poor-risk features.