Dose comparison of robustly optimized intensity modulated proton therapy (IMPT) vs IMRT and VMAT photon plans for testicular seminoma.

BACKGROUND: Patients with stage II seminoma have traditionally been treated with photons to the retroperitoneal and iliac space, which leads to a substantial dose bath to abdominal and pelvic organs at risk (OAR). As these patients are young and with excellent prognosis, reducing dose to OAR and thereby the risk of secondary cancer is of utmost importance. We compared IMPT to opposing IMRT fields and VMAT, assessing dose to OAR and both overall and organ-specific secondary cancer risk. MATERIAL AND METHODS: A comparative treatment planning study was conducted on planning CT-scans from ten patients with stage II seminoma, treated with photons to a 'dog-leg' field with doses ranging from 20 to 25 Gy and a 10 Gy sequential boost to the metastatic lymph node(s). Photon plans were either 3-4 field IMRT (Eclipse) or 1-2 arc VMAT (Pinnacle). Proton plans used robust (5 mm; 3.5%) IMPT (Eclipse), multi field optimization with 3 posterior fields supplemented by 2 anterior fields at the level of the iliac vessels. Thirty plans were generated. Mean doses to OARs were compared for IMRT vs IMPT and VMAT vs IMPT. The risk of secondary cancer was calculated according to the model described by Schneider, using excess absolute risk (EAR, per 10,000 persons per year) for body outline, stomach, duodenum, pancreas, bowel, bladder and spinal cord. RESULTS: Mean doses to all OARs were significantly lower with IMPT except similar kidney (IMRT) and spinal cord (VMAT) doses. The relative EAR for body outline was 0.59 for IMPT/IMRT (p < .05) and 0.33 for IMPT/VMAT (p < .05). Organ specific secondary cancer risk was also lower for IMPT except for pancreas and duodenum. CONCLUSION: Proton therapy reduced radiation dose to OAR compared to both IMRT and VMAT plans, and potentially reduce the risk of secondary cancer both overall and for most OAR.

Can whole-body MRI replace CT in management of metastatic testicular cancer? A prospective, non-inferiority study.

PURPOSE: Concerns of imaging-related radiation exposure in young patients with high survival rates have increased the use of magnetic resonance imaging (MRI) in testicular cancer (TC) stage I. However, computed tomography (CT) is still preferred for metastatic TC. The purpose of this study was to compare whole-body MRI incl. diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) with contrast-enhanced, thoracoabdominal CT in metastatic TC. METHODS: A prospective, non-inferiority study of 84 consecutive patients (median age 33 years) with newly diagnosed metastatic TC (February 2018-January 2021). Patients had both MRI and CT before and after treatment. Anonymised images were reviewed by experienced radiologists. Lesion malignancy was evaluated on a Likert scale (1 benign-4 malignant). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated on patient and lesion level. The primary outcome was demonstrating non-inferiority regarding sensitivity of MRI compared to CT. The non-inferiority margin was set at 5%. ROC curves and interobserver agreement were calculated. RESULTS: On patient level, MRI had 98% sensitivity and 75% specificity compared to CT. On lesion level within each modality, MRI had 99% sensitivity and 78% specificity, whereas CT had 98% sensitivity and 88% specificity. MRI sensitivity was non-inferior to CT (difference 0.57% (95% CI - 1.4-2.5%)). The interobserver agreement was substantial between CT and MRI. CONCLUSION: MRI with DWIBS was non-inferior to contrast-enhanced CT in detecting metastatic TC disease. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT03436901, finished July 1st 2021.

Implications for Efficacy and Safety of Total Dose and Dose-Intensity of Neoadjuvant Gemcitabine-Cisplatin in Muscle-Invasive Bladder Cancer: Three-Week Versus Four-Week Regimen.

BACKGROUND: Neoadjuvant cisplatin-based chemotherapy is standard care prior to radical cystectomy in patients with muscle-invasive bladder cancer (MIBC). OBJECTIVE: To assess efficacy and safety of two commonly used neoadjuvant schedules with different total doses and dose-intensities of gemcitabine and cisplatin (GC). METHODS: Data were collected retrospectively from all patients treated between 2010 and 2018 with neoadjuvant chemotherapy according to clinical routine at seven centres in Sweden and Denmark. Patients in Sweden received three cycles of a 4-week schedule (GC-4w: cisplatin 70 mg/m2 day 1, gemcitabine 1000 mg/m2 days 1, 8, 15, q 28 days) and in Denmark four cycles of a 3-week schedule (GC-3w: cisplatin 70 mg/m2 day 1, gemcitabine 1000 mg/m2 days 1, 8, q 21 days). Primary endpoint was pathological response at cystectomy (pT0N0 and < pT2N0). RESULTS: A total of 251 patients were treated with GC-4w and 455 with GC-3w. pT0N0 was significantly higher for patients treated with GC-3w compared to GC-4w, 46% versus 32% (adjusted odds ratio [aOR] 1.80; 95% confidence interval [CI] 1.16-2.80; P = 0.009); and for < pT2N0 60% versus 47% (aOR 1.08; 95% CI 0.70-1.66; P = 0.743). There were no significant differences between GC-4w and GC-3w regarding survival parameters. GC-3w patients discontinued treatment more frequently and showed a higher degree of neutropenia. CONCLUSIONS: A significantly higher complete response-rate was observed in the patient group treated with the more cisplatin-dose-intense 3-week schedule. The side-effect profile was in favor of the 4-week approach while relapse-free and overall survival were similar.

Real-world Treatment Patterns and Overall Survival in Locally Advanced and Metastatic Urothelial Tract Cancer Patients Treated with Chemotherapy in Denmark in the Preimmunotherapy Era: A Nationwide, Population-based Study.

BACKGROUND: Real-world treatment patterns and survival outcomes of locally advanced, unresectable, and metastatic urinary tract cancer (mUTC) patients have not previously been studied in a nationwide, population-based cohort. OBJECTIVE: To describe treatment patterns and survival outcomes in mUTC patients treated in the real-world clinical setting. DESIGN SETTING AND PARTICIPANTS: This nationwide, population-based study included all mUTC patients initiating first-line chemotherapy at Danish oncology departments from January 2010 to March 2016. Data were retrospectively obtained from electronic medical records. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcome measurements were descriptive. Kaplan-Meier was used for survival analysis. RESULTS AND LIMITATIONS: Of 952 patients included in the study, 46.2% initiated standard gemcitabine/cisplatin (GC) and 21.1% gemcitabine/carboplatin (CaG); the remaining patients initiated other treatment regimens. Median follow-up was 11.6 mo. The overall response rate and disease control rate were 43.0% and 61.7% in all patients, 51.4% and 69.1% in GC-treated patients, and 34.4% and 58.8% in CaG-treated patients, respectively. Median overall survival (OS) was 11.7 (95% confidence interval [CI]: 10.8-12.5) mo in all patients, 14.0 (95% CI: 12.5-15.5) mo in GC-treated patients, and 9.8 (95% CI: 8.7-10.9) mo in CaG-treated patients. Limitations include the retrospective study design. CONCLUSIONS: Real-world mUTC patients are older and less fit than patients enrolled in clinical trials; despite this, tumor responses and survival are comparable. Survival in our patient cohort is also comparable with that reported from other real-world studies in this patient group. PATIENT SUMMARY: We studied treatment patterns and survival in urinary tract cancer patients receiving chemotherapy in the real-world clinical practice. Survival in our patient cohort was comparable with that reported from clinical trials and other real-world studies in this patient group.

A case of severe side effect due to muscle oil injections in combination with chemotherapy in a former bodybuilder.

This case report presents an acute painful skin reaction several years after injection of site-enhancing oils (SEO) induced by chemotherapy. This case exemplifies the long-term dangerous side effects of the use of SEO, however treatable with prednisolone.

Real-World Study of Treatment with Pembrolizumab Among Patients with Advanced Urothelial Tract Cancer in Denmark.

BACKGROUND: Investigating the effect of newly approved oncological drugs in the real-world is warranted. With emerging novel treatments rapidly being approved for urothelial tract cancers, we aimed to assess real-world data, regarding effect and safety, during the first year after approval of pembrolizumab in Denmark for patients with locally advanced and unresectable or metastatic urothelial tract cancer (mUTC) in the first- and second-line setting. MATERIALS AND METHOD: At the six oncological departments treating mUTC in Denmark, we identified all mUTC patients receiving pembrolizumab during the first year after approval, between March 1, 2018 and February 28, 2019. A retrospective data collection was conducted from January to June 2020. Patient characteristics matching that of the relevant clinical trials for pembrolizumab in first- and second-line treatment-setting, overall survival (OS), progression-free survival (PFS), toxicity and tumor response were assessed. RESULTS: 139 patients were identified, 53 in first-line treatment, 77 in second-line, and 9 receiving third or later lines of treatment. The population was characterized by a majority of males (70%), most patients had ECOG PS 0-1 (60.4%) and primary tumor in the bladder was predominant (90.6%). The overall response rate (ORR) in first-line was 30.2%, PFS was 3,5 months (95%CI 2,3-7,9 months) and OS 9,2 months (95%CI 7,0-20.9 months). For second-line treatment the ORR was 27,3%, PFS 2,9 months (95%CI 2,5-5,3) and OS 9.1 months (95%CI 5,4-12,8 months). Toxicity was comparable to clinical trials without any new toxicities registered. CONCLUSION: Real-world data on response rates, OS, PFS and toxicity for patients with mUTC receiving pembrolizumab in first- and second-line, shows comparable results to clinical trials. This study further establishes immunotherapy as an effective and tolerable treatment for mUTC.

DaPeCa-4: outcome in penile cancer patients with N3 disease due to extra nodal extension treated with surgery and chemo-irradiation.

Objective: The role of pelvic lymph node dissection (PLND) is still debated in patients with N3 stage penile cancer. In Denmark this subgroup of patients is in general managed with an inguinal lymphadenectomy (ILND) and adjuvant chemoradiation and PLND is not offered as a standard. The objective of this study was to report treatment outcomes of this regimen and compare this with existing literature.Materials and methods: We retrospectively reviewed records of patients with pT1-T4, N3, M0 penile cancer diagnosed between 1st January 2010 and 31th December 2014 in Denmark and treated with curative intend.Results: 21 patients were identified with a median follow up of 74 months (CI 54-94). Management of the penile lesion was local resection in 5 (23.8%), partial penectomy in 10 (47.6%), and total penectomy in 6 (28.6%) of patients. Regarding the most extensive lymph node (LN) surgery: 4 patients (23,8%) went directly to oncological treatment from sentinel node biopsy with no further LN dissection, 6 patients (28.6%) were treated with unilateral ILND, 10 patients (47.6%) with bilateral ILND and a single patient (4.8%) was treated with ILND and PLND. In the adjuvant setting patients were treated with external beam therapy of involved regions and cisplatin-based chemotherapy. Median overall survival was 84 months (CI 0-176). The 5-year probability of surviving penile cancer was 57.1% (CI 36.0-78.3).Conclusion: Treatment with surgery and chemo-irradiation in this national cohort does not show inferior survival outcomes compared to historical cohorts.

Gemcitabine and cisplatin in locally advanced and metastatic bladder cancer; 3- or 4-week schedule?

BACKGROUND: Chemotherapy with gemcitabine and cisplatin (GC) is an active regimen in advanced transitional cell carcinoma (TCC). Traditionally, GC has been administered as a 4-week schedule. However, an alternative 3-week schedule may be more feasible. Long-term survival data for the alternative 3-week schedule and comparisons of the feasibility and toxicity between the two schedules have not previously been published. MATERIAL AND METHODS: We performed a retrospective analysis of patients with stage IV TCC, treated with GC by a standard 4-week or by an alternative 3-week schedule. RESULTS: A total of 212 patients received GC (3-week; n = 151, 4-week; n = 61). We found no statistical differences in overall survival between the two schedules (hazard ratio 1.15, 95% CI 0.83-1.59), p = 0.40). Five-year survival rates were 14.9% and 11.8% for the 3- and 4-week schedule, respectively (p = 0.94). Response rates were 59.7% and 55.6%, respectively (p = 0.61). Toxicity was less pronounced in the 3-week schedule with regards to neutropenia, thrombocytopenia, and transfusion rates. Hematologic toxicity at day 15 in the 4-week schedule was common, leading to dose omissions in 47% of cycles. Dose intensity for gemcitabine was accordingly lower in the 4 week-schedule. The higher dose intensity of cisplatin in the 3-week schedule, did not lead to increased renal toxicity. In 13 patients with impaired renal function, cisplatin was split into 2 days, which was feasible and efficient. CONCLUSION: Efficacy parameters for the GC 3-week schedule were comparable to those for the 4-week schedule, whereas toxicity was less pronounced. The 3-week schedule may be an effective and feasible alternative GC-schedule.

Long-term survival after gemcitabine and cisplatin in patients with locally advanced transitional cell carcinoma of the bladder: focus on supplementary treatment strategies.

OBJECTIVE: The objective was to evaluate response and survival, as well as efficacy of subsequent supplementary treatment and follow-up strategy in patients with locally advanced transitional cell carcinoma of the bladder following combination chemotherapy with gemcitabine and cisplatin (GC). METHODS: A total of 84 patients with locally advanced (T4b, Nx, M0 or Tx, N2-3, M0) received GC. After chemotherapy, the strategy was close surveillance in patients with complete response, and supplementary radical cystectomy or radiotherapy whenever possible in patients with partial response. RESULTS: A total of 25 patients (29.8%) with complete response to chemotherapy were followed by close surveillance. This group achieved a median overall survival of 47.6 mo. Another 25 patients had partial response to chemotherapy. Of these patients, 16 had supplementary treatment, with 10 achieving "no evidence of disease" (NED). Thus, a total of 35 patients achieved NED with a median overall survival of 48.7 mo versus 10.2 mo in patients not achieving NED (hazard ratio=0.10; 95%CI, 0.05-0.20; p<0.0001). The rate of NED was higher in the group of patients who had a cystectomy compared with the group who received radiotherapy as supplementary treatment. CONCLUSIONS: In patients with locally advanced bladder cancer, NED following chemotherapy alone or chemotherapy plus supplementary cystectomy or radiotherapy is essential to achieve long-term survival. Patients with a partial response should be offered radical cystectomy whenever possible, which seems to be superior to radiotherapy. Close surveillance may be an alternative to immediate cystectomy in patients with complete response following chemotherapy.