Adenoid Cystic Cancer of the Lacrimal Gland: Management Aspects and Treatment Outcomes.

Adenoid cystic carcinoma (ACC) of the lacrimal gland is the most common malignant epithelial tumor of the lacrimal gland. The biological behavior of these tumors is characterized by a slow growth with frequent nerve invasion but rare invasion of the neck nodes. Local extension intracranially with bone erosions is seen in locally advanced tumors. Distant metastasis to lungs bone and liver are commonly reported. Treatments using surgery and radiotherapy are generally preferred for adequate tumor control. However there is still no consensus on the best treatment approach. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04426-5.

Pilot Evaluation of Perioperative High Dose Rate Brachytherapy in Head Neck Cancers.

Perioperative high dose rate brachytherapy involves insertion of brachytherapy catheter over the tumor bed during surgical removal of disease followed by radiation in the postoperative period. It has applications in radiotherapy dose escalation or reirradiation and for extending the surgical margins. We report here initial results of treatment in five cases of locally advanced head and neck cancers.

Standard Versus Modified Ipilimumab, in Combination With Nivolumab, in Advanced Renal Cell Carcinoma: A Randomized Phase II Trial (PRISM).

PURPOSE: Ipilimumab (IPI), in combination with nivolumab (NIVO), is an approved frontline treatment option for patients with intermediate- or poor-risk advanced renal cell carcinoma (aRCC). We conducted a randomized phase II trial to evaluate whether administering IPI once every 12 weeks (modified), instead of once every 3 weeks (standard), in combination with NIVO, is associated with a favorable toxicity profile. METHODS: Treatment-naïve patients with clear-cell aRCC were randomly assigned 2:1 to receive four doses of modified or standard IPI, 1 mg/kg, in combination with NIVO (3 mg/kg). The primary end point was the proportion of patients with a grade 3-5 treatment-related adverse event (trAE) among those who received at least one dose of therapy. The key secondary end point was 12-month progression-free survival (PFS) in the modified arm compared with historical sunitinib control. The study was not designed to formally compare arms for efficacy. RESULTS: Between March 2018 and January 2020, 192 patients (69.8% intermediate/poor-risk) were randomly assigned and received at least one dose of study drug. The incidence of grade 3-5 trAEs was significantly lower among participants receiving modified versus standard IPI (32.8% v 53.1%; odds ratio, 0.43 [90% CI, 0.25 to 0.72]; P = .0075). The 12-month PFS (90% CI) using modified IPI was 46.1% (38.6 to 53.2). At a median follow-up of 21 months, the overall response rate was 45.3% versus 35.9% and the median PFS was 10.8 months versus 9.8 months in the modified and standard IPI groups, respectively. CONCLUSION: Rates of grade 3-5 trAEs were significantly lower in patients receiving modified versus standard IPI. Although 12-month PFS did not meet the prespecified efficacy threshold compared with historical control, informal comparison of treatment groups did not suggest any reduction in efficacy with the modified schedule.

Bench to Bedside Development of [18F]Fluoromethyl-(1,2-2H4)choline ([18F]D4-FCH).

Malignant transformation is characterised by aberrant phospholipid metabolism of cancers, associated with the upregulation of choline kinase alpha (CHKα). Due to the metabolic instability of choline radiotracers and the increasing use of late-imaging protocols, we developed a more stable choline radiotracer, [18F]fluoromethyl-[1,2-2H4]choline ([18F]D4-FCH). [18F]D4-FCH has improved protection against choline oxidase, the key choline catabolic enzyme, via a 1H/2D isotope effect, together with fluorine substitution. Due to the promising mechanistic and safety profiles of [18F]D4-FCH in vitro and preclinically, the radiotracer has transitioned to clinical development. [18F]D4-FCH is a safe positron emission tomography (PET) tracer, with a favourable radiation dosimetry profile for clinical imaging. [18F]D4-FCH PET/CT in lung and prostate cancers has shown highly heterogeneous intratumoral distribution and large lesion variability. Treatment with abiraterone or enzalutamide in metastatic castrate-resistant prostate cancer patients elicited mixed responses on PET at 12-16 weeks despite predominantly stable radiological appearances. The sum of the weighted tumour-to-background ratios (TBRs-wsum) was associated with the duration of survival.

Symptomatic Deep Vein Thrombosis Associated With Peripherally Inserted Central Catheters of Different Diameters: A Systematic Review and Meta-Analysis.

We assessed the relationship between peripherally inserted central catheter (PICC) diameters and symptomatic deep vein thrombosis (DVT) rates. We conducted a systematic search for articles published between 2010 and 2021 reporting DVT incidence by catheter diameter in patients who had a PICC, followed by meta-analyses for DVT risk in each diameter group. Pooled DVT rates were incorporated into an economic model. Of 1627 abstracts screened, 47 studies were included. The primary meta-analysis of 40 studies demonstrated the incidence of DVT was 0.89%, 3.26%, 5.46%, and 10.66% for 3, 4, 5, and 6 French (Fr) PICCs (P = .01 between 4 and 5 Fr). Rates of DVT were not significantly different between oncology and nononcology patients (P = .065 for 4 Fr and P = .99 for 5 Fr). The DVT rate was 5.08% for ICU patients and 4.58% for non-ICU patients (P = .65). The economic model demonstrated an annual, incremental cost savings of US$114 053 for every 5% absolute reduction in 6 Fr PICCs use. Using the smallest PICC that meets the patients' clinical needs may help to mitigate risks and confer savings.

Using the AR-V7 biomarker to determine treatment in metastatic castrate resistant prostate cancer, a feasibility randomised control trial, conclusions from the VARIANT trial [version 2; peer review: 2 approved].

Background: Prostate cancer is the most commonly diagnosed malignancy in the UK. Castrate resistant prostate cancer (CRPC) can be difficult to manage with response to next generation hormonal treatment variable. AR-V7 is a protein biomarker that can be used to predict response to treatment and potentially better inform management in these patients. Our aim was to establish the feasibility of conducting a definitive randomised controlled trial comparing the clinical utility of AR-V7 biomarker assay in personalising treatments for patients with metastatic CRPC within the United Kingdom (UK) National Health Service (NHS).  Due to a number of issues the trial was not completed successfully, we aim to discuss and share lessons learned herein. Methods: We conducted a randomised, open, feasibility trial, which aimed to recruit 70 adult men with metastatic CRPC within three secondary care NHS trusts in the UK to be run over an 18-month period. Participants were randomised to personalised treatment based on AR-V7 status (intervention) or standard care (control). The primary outcome was feasibility, which included: recruitment rate, retention and compliance. Additionally, a baseline prevalence of AR-V7 expression was to be estimated. Results: Fourteen participants were screened and 12 randomised with six into each arm over a nine-month period. Reliability issues with the AR-V7 assay meant prevalence was not estimated. Due to limited recruitment the study did not complete to target. Conclusions: Whilst the trial did not complete to target, we have ascertained that men with advanced cancer are willing to take part in trials utilising biomarker guided treatment. A number of issues were identified that serve as important learning points in future clinical trials.

Eligibility for 177Lu-PSMA Therapy Depends on the Choice of Companion Diagnostic Tracer: A Comparison of 68Ga-PSMA-11 and 99mTc-MIP-1404 in Metastatic Castration-Resistant Prostate Cancer.

177Lu-prostate-specific membrane antigen-617 (177Lu-PSMA-617) is an effective therapy for metastatic castration-resistant prostate cancer (mCRPC), with evidence of improved survival over standard care. The VISION trial inclusion criteria required a metastatic lesion-to-liver ratio of greater than 1 on 68Ga-PSMA-11 PET scans. We aimed to determine whether an equivalent ratio is suitable for a SPECT tracer, 99mTc-MIP-1404, and to compare lesion and lesion-to-normal-organ ratios between the 2 radiotracers. Methods: Two cohorts of patients with mCRPC matched for age, prostate-specific antigen level, and total Gleason score, with either 99mTc-MIP-1404 SPECT/CT (n = 25) or 68Ga-PSMA-11 PET/CT (n = 25) scans, were included for analysis. Up to 3 lesions in each site (prostate/prostate bed, lymph nodes, bone and soft-tissue metastases) as well as normal liver, parotid gland, spleen, and mediastinal blood-pool SUVmax were measured. Results: 99mTc-MIP-1404 SPECT lesion SUVmax was not significantly different from 68Ga-PSMA-11 PET (median, 18.2 vs. 17.3; P = 0.93). However, 99mTc-MIP-1404 liver SUVmax was higher (median, 8.5 vs. 5.8; P = 0.002) and lesion-to-liver ratios were lower (median, 2.7 vs. 3.5; P = 0.009). There was no significant difference in parotid gland or splenic SUVmax or lesion-to-parotid gland ratios between the 2 tracers although there was a small difference in lesion-to-spleen ratios (P = 0.034). Conclusion: There are differences in biodistribution and, in particular, liver activity, between 68Ga-PSMA-11 and 99mTc-MIP-1404. Therefore, if 99mTc-MIP-1404 is used to assess eligibility for 177Lu-PSMA-617 therapy, a lower adjusted lesion-to-liver ratio should be used.

Personalised versus non-individualised case-based CME: A randomised pilot study.

The PinPoint Case Platform (PPCP) offers independent online case-based CME. To align with personal learning needs, a functionality of needs assessments ("QuickScan") was developed, directing users to follow personalised case journeys. A randomised study was conducted, comparing its effectiveness, time efficiency and user experience with a format of non-individualised case-based learning. Forty-two residents in urology from five European countries were randomly assigned to follow non-individualised case-based learning (control group) or a needs assessment plus personalised case journeys on different topics in prostate cancer. After performing a pre- and post-assessment, both groups showed a similar increase in test scores (Mann-Whitney U = 247; p = .113), but the time needed for completing the learning exercise was significantly lower in the group with the personalised approach (median: 45 vs 90 minutes; Mann-Whitney U = 97.5; p = .0141). The quality of the two learning methods was similarly well received by both groups. In conclusion, learners who followed personalised case journeys learned similarly effective but more time efficient than non-individualised case-based learners. Future studies should determine if these findings can be extrapolated to board-certified physicians following CME activities.

Concept: A randomised multicentre trial of first line chemotherapy comparing three weekly cabazitaxel versus weekly paclitaxel in HER2 negative metastatic breast cancer.

BACKGROUND: Paclitaxel is commonly used as first-line chemotherapy for HER2-negative metastatic breast cancer (MBC) patients. However, with response rates of 21.5-53.7% and significant risk of peripheral neuropathy, there is need for better chemotherapy. PATIENTS AND METHODS: This open-label phase II/III trial randomised HER2-negative MBC patients 1:1 to either 6 cycles of three-weekly cabazitaxel (25 mg/m2), or, weekly paclitaxel (80 mg/m2) over 18 weeks. The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), time to response (TTR), overall survival (OS), safety and tolerability and quality of life (QoL). RESULTS: 158 patients were recruited. Comparing cabazitaxel to paclitaxel, median PFS was 6.7 vs 5.8 months (HR 0.87; 80%CI 0.70-1.08, P = 0.4). There was no difference in median OS (20.6 vs 18.2 months, HR 1.00; 95%CI 0.69-1.45, P = 0.99), ORR (41.8% vs 36.7%) or TTR (HR 1.09; 95%CI 0.68-1.75, P = 0.7). Grade ≥3 adverse events occurred in 41.8% on cabazitaxel and 46.8% on paclitaxel; the most common being neutropenia (16.5%) and febrile neutropenia (12.7%) cabazitaxel and neutropenia (8.9%) and lung infection (7.6%) paclitaxel. Peripheral neuropathy of any grade occurred in 54.5% paclitaxel vs 16.5% cabazitaxel. Mean EQ-5D-5L single index utility score (+0.05; 95%CI 0.004-0.09, P = 0.03) and visual analogue scale score (+7.7; 95%CI 3.1-12.3, P = 0.001) were higher in cabazitaxel vs paclitaxel. CONCLUSIONS: Three-weekly cabazitaxel in HER2-negative MBC does not significantly improve PFS compared to weekly paclitaxel, although it has a lower risk of peripheral neuropathy with better patient reported QoL outcomes. It is well tolerated and requires fewer hospital visits.

Prostate cancer-Exercise and Metformin Trial (Pre-EMpT): study protocol for a feasibility factorial randomized controlled trial in men with localised or locally advanced prostate cancer.

BACKGROUND: Evidence from observational studies have shown that moderate intensity physical activity can reduce risk of progression and cancer-specific mortality in participants with prostate cancer. Epidemiological studies have also shown participants taking metformin to have a reduced risk of prostate cancer. However, data from randomised controlled trials supporting the use of these interventions are limited. The Prostate cancer-Exercise and Metformin Trial examines that feasibility of randomising participants diagnosed with localised or locally advanced prostate cancer to interventions that modify physical activity and blood glucose levels. The primary outcomes are randomisation rates and adherence to the interventions over 6 months. The secondary outcomes include intervention tolerability and retention rates, measures of insulin-like growth factor I, prostate-specific antigen, physical activity, symptom-reporting, and quality of life. METHODS: Participants are randomised in a 2 × 2 factorial design to both a physical activity (brisk walking or control) and a pharmacological (metformin or control) intervention. Participants perform the interventions for 6 months with final measures collected at 12 months follow-up. DISCUSSION: Our trial will determine whether participants diagnosed with localised or locally advanced prostate cancer, who are scheduled for radical treatments or being monitored for signs of cancer progression, can be randomised to a 6 months physical activity and metformin intervention. The findings from our trial will inform a larger trial powered to examine the clinical benefits of these interventions. TRIAL REGISTRATION: Prostate Cancer Exercise and Metformin Trial (Pre-EMpT) is registered on the ISRCTN registry, reference number ISRCTN13543667 . Date of registration 2nd August 2018-retrospectively registered. First participant was recruited on 11th September 2018.

Delphi study to identify consensus on patient selection for hydrogel rectal spacer use during radiation therapy for prostate cancer in the UK.

OBJECTIVES: To identify consensus on patient prioritisation for rectal hydrogel spacer use during radiation therapy for the treatment of prostate cancer in the UK. DESIGN: Delphi study consisting of two rounds of online questionnaires, two virtual advisory board meetings and a final online questionnaire. SETTING: Radical radiation therapy for localised and locally advanced prostate cancer in the UK. PARTICIPANTS: Six leading clinical oncologists and one urologist from across the UK. INTERVENTIONS: Rectal hydrogel spacer. PRIMARY AND SECONDARY OUTCOME MEASURES: None reported. RESULTS: The panel reached consensus on the importance of minimising toxicity for treatments with curative intent and that even low-grade toxicity-related adverse events can significantly impact quality of life. There was agreement that despite meeting rectal dose constraints, too many patients experience rectal toxicity and that rectal hydrogel spacers in eligible patients significantly reduces toxicity-related adverse events. However, as a consequence of funding limitations, patients need to be prioritised for spacer use. A higher benefit of spacers can be expected in patients on anticoagulation and in patients with diabetes or inflammatory bowel disease, but consensus could not be reached regarding patient groups expected to benefit less. While radiation therapy regimen is not a main factor determining prioritisation, higher benefit is expected in ultrahypofractionated regimens. CONCLUSION: There is a strong and general agreement that all patients with prostate cancer undergoing radical radiation therapy have the potential to benefit from hydrogel spacers. Currently, not all patients who could potentially benefit can access hydrogel spacers, and access is unequal. Implementation of the consensus recommendations would likely help prioritise and equalise access to rectal spacers for patients in the UK.

The impact of hegemonic masculine ideals on self-esteem in prostate cancer patients undergoing androgen deprivation therapy (ADT) compared to ADT-naïve patients.

PURPOSE: Androgen deprivation therapy (ADT) for Prostate Cancer (PCa) is associated with side effects that could lead to negative body image and low masculine self-esteem of survivors. We compared a group of PCa survivors following ADT with ADT-naïve patients, expecting the ADT group to show lower masculine self-esteem. We also expected patients with hegemonic masculinity ideals to show poorer masculine self-esteem and we hypothesized that ADT would moderate this relationship, expecting PCa patients on ADT with stronger hegemonic ideals to show the worst masculine self-esteem scores among study participants. METHODS: We compared 57 PCa survivors on ADT (Mage  = 64.16 (7.11)) to 59 ADT-naïve patients (Mage  = 65.25 (5.50)), on the Masculine Self-Esteem Scale (MSES), Body Image Scale (BIS), and Hegemonic Masculinity Ideals Scale (HMIS). RESULTS: While the two groups did not significantly differ on masculine self-esteem (F [1, 115] = 3.46, p = 0.065, ηp 2  = 0.029) and body image (F [1, 115] = 3.46, p = 0.065, ηp 2  = 0.029), younger age was significantly associated with higher body image issues (F [1, 115] = 8.63, p < 0.01, ηp 2  = 0.071, ß = -0.30). Hegemonic masculinity significantly predicted more masculine self-esteem related issues (t (2, 114) = 2.31, ß = 0.375, p < 0.05). ADT did not moderate this relationship. CONCLUSIONS: The results suggest that endorsing hegemonic masculinity could represent a risk factor for low masculine self-esteem regardless of ADT status and that younger age is associated with negative body image among PCa survivors. IMPLICATIONS: These results suggest the importance of inclusion of topics related to hegemonic masculinity when providing support to PCa survivors, both when discussing treatment side effects, as well as in the later phases of survivorship. This pilot also suggests that younger PCa survivors might benefit from body-image focused support regardless of treatment plan.

Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial.

BACKGROUND: STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL). METHODS AND FINDINGS: Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively. CONCLUSIONS: Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC. TRIAL REGISTRATION: ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544.

Attitudes and adherence to changes in nutrition and physical activity following surgery for prostate cancer: a qualitative study.

OBJECTIVES: Interventions designed to improve men's diet and physical activity (PA) have been recommended as methods of cancer prevention. However, little is known about specific factors that support men's adherence to these health behaviour changes, which could inform theory-led diet and PA interventions. We aimed to explore these factors in men following prostatectomy for prostate cancer (PCa). DESIGN, SETTING AND PARTICIPANTS: A qualitative study using semistructured interviews with men, who made changes to their diet and/or PA as part of a factorial randomised controlled trial conducted at a single hospital in South West England. Participants were 17 men aged 66 years, diagnosed with localised PCa and underwent prostatectomy. Interview transcripts underwent thematic analysis. RESULTS: Men were ambivalent about the relationship of nutrition and PA with PCa risk. They believed their diet and level of PA were reasonable before being randomised to their interventions. Men identified several barriers and facilitators to performing these new behaviours. Barriers included tolerance to dietary changes, PA limitations and external obstacles. Facilitators included partner involvement in diet, habit formation and brisk walking as an individual activity. Men discussed positive effects associated with brisk walking, such as feeling healthier, but not with nutrition interventions. CONCLUSIONS: The facilitators to behaviour change suggest that adherence to trial interventions can be supported using well-established behaviour change models. Future studies may benefit from theory-based interventions to support adherence to diet and PA behaviour changes in men diagnosed with PCa.

Efficacy and Safety of Autologous Dendritic Cell-Based Immunotherapy, Docetaxel, and Prednisone vs Placebo in Patients With Metastatic Castration-Resistant Prostate Cancer: The VIABLE Phase 3 Randomized Clinical Trial.

IMPORTANCE: DCVAC/PCa is an active cellular immunotherapy designed to initiate an immune response against prostate cancer. OBJECTIVE: To evaluate the efficacy and safety of DCVAC/PCa plus chemotherapy followed by DCVAC/PCa maintenance treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). DESIGN, SETTING, AND PARTICIPANTS: The VIABLE double-blind, parallel-group, placebo-controlled, phase 3 randomized clinical trial enrolled patients with mCRPC among 177 hospital clinics in the US and Europe between June 2014 and November 2017. Data analyses were performed from December 2019 to July 2020. INTERVENTIONS: Eligible patients were randomized (2:1) to receive DCVAC/PCa (add-on and maintenance) or placebo, both in combination with chemotherapy (docetaxel plus prednisone). The stratification was applied according to geographical region (US or non-US), prior therapy (abiraterone, enzalutamide, or neither), and Eastern Cooperative Oncology Group performance status (0-1 or 2). DCVAC/PCa or placebo was administered subcutaneously every 3 to 4 weeks (up to 15 doses). MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival (OS), defined as the time from randomization until death due to any cause, in all randomized patients. Survival was compared using 2-sided log-rank test stratified by geographical region, prior therapy with abiraterone and/or enzalutamide, and Eastern Cooperative Oncology Group performance status. RESULTS: A total of 1182 men with mCRPC (median [range] age, 68 [46-89] years) were randomized to receive DCVAC/PCa (n = 787) or placebo (n = 395). Of these, 610 (81.8%) started DCVAC/PCa, and 376 (98.4%) started placebo. There was no difference in OS between the DCVAC/PCa and placebo groups in all randomized patients (median OS, 23.9 months [95% CI, 21.6-25.3] vs 24.3 months [95% CI, 22.6-26.0]; hazard ratio, 1.04; 95% CI, 0.90-1.21; P = .60). No differences in the secondary efficacy end points (radiological progression-free survival, time to prostate-specific antigen progression, or skeletal-related events) were observed. Treatment-emergent adverse events related to DCVAC/PCa or placebo occurred in 69 of 749 (9.2%) and 48 of 379 (12.7%) patients, respectively. The most common treatment-emergent adverse events (DCVAC/PCa [n = 749] vs placebo [n = 379]) were fatigue (271 [36.2%] vs 152 [40.1%]), alopecia (222 [29.6%] vs 130 [34.3%]), and diarrhea (206 [27.5%] vs 117 [30.9%]). CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, DCVAC/PCa combined with docetaxel plus prednisone and continued as maintenance treatment did not extend OS in patients with mCRPC and was well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02111577.

ROLE OF ANDROGEN RECEPTOR-TARGETED AGENTS IN LOCALIZED PROSTATE CANCER.

Anti-androgen therapy continues to be a basic pilar of treatment for both localized and metastatic prostate cancer. The advent of new generation of androgen receptor targeted agents (ARTA) transformed the care of patients with advanced disease. After such a success, the steps were taken to incorporate a new generation of ARTAs into the treatment landscape of localized prostate cancer. High-risk prostate cancer represents the most aggressive form of localized disease with significant metastatic potential and poor outcome. Here, the impact of novel therapies will likely be profound and transforming. This clinical space has already been a showcase for multidisciplinary treatment where the combination of local therapies with systemic treatment gradually improved patient outcomes and the chances of cure. The most recent step in redefining the treatment of localized disease is the adoption of novel ARTAs moving forward the multidisciplinary platform. In this narrative review, we discuss current clinical evidence supporting the use of novel ARTAs in patients with localized high-risk prostate cancer and cover recent developments in biomarker-driven strategies for treatment individualization in this clinical context.

VinCaP: a phase II trial of vinflunine in locally advanced and metastatic squamous carcinoma of the penis.

BACKGROUND: We investigated the first-line activity of vinflunine in patients with penis cancer. Cisplatin-based combinations are commonly used, but survival is not prolonged; many patients are unfit for such treatment or experience toxicity that outweighs clinical benefit. METHODS: Twenty-five patients with inoperable squamous carcinoma of the penis were recruited to a single-arm, Fleming-A'Hern exact phase II trial. Treatment comprised 4 cycles of vinflunine 320 mg/m2, given every 21 days. Primary endpoint was clinical benefit rate (CBR: objective responses plus stable disease) assessed after 4 cycles. Seven or more objective responses or disease stabilisations observed in 22 evaluable participants would exclude a CBR of <15%, with a true CBR of >40% being probable. RESULTS: Twenty-two participants were evaluable. Ten objective responses or disease stabilisations were confirmed. CBR was 45.5%, meeting the primary endpoint; partial response rate was 27.3%. Seven patients received >4 cycles of vinflunine. Dose reduction or treatment delay was required for 20% of cycles. In all, 68% of patients experienced at least one grade 3 adverse event. Two deaths on treatment were not caused by disease progression. CONCLUSIONS: Pre-specified clinical activity threshold was exceeded. Toxicity was in keeping with experience in other tumours. Vinflunine merits further study in this disease. TRIAL REGISTRATION: NCT02057913.

Prognostic Value of HPV Infection Assessed by p16 Immunohistochemistry and the Influence of Tobacco Usage in Oropharyngeal Cancers: Real World Scenario.

To find if an association could be established between Human Papilloma Virus (HPV) infection and oropharyngeal cancers (OPCs) in a group of patients known to be regular users of tobacco, and to determine the impact of HPV status on clinical outcomes.Case records of 212 patients with AJCC-7 (The American Joint Committee on Cancer 7th edition) stages II-IVB non metastatic squamous cell carcinoma of the oropharynx treated using radical radiotherapy with or without chemotherapy during the years 2015-2018 were retrieved. Formalin-fixed, paraffin-embedded blocks from oropharyngeal biopsies were available for 177 patients and were evaluated for p16 expression by immunohistochemical (IHC) staining. More than 50% nuclear staining with or without cytoplasmic staining was considered HPV+ . The association between tobacco use and HPV, as well as the influence of HPV status on survival outcomes were assessed. p16 expression was found to be positive in 23(13%) patients. Significant association was found between chewable tobacco usage and HPV positivity (p = 0.051). The median follow up was 20.5 months (range: 3-80). 5-year Overall Survival was 43.4% and 29.8% (p = 0.044) in HPV+ and HPV- patients, respectively. Local control was significantly better in HPV+ patients (38.6% vs. 25.3%, p = 0.049). There was also a trend towards improved Disease-free Survival in HPV+ patients (31 months vs. 15 months, p = 0.078). Though less in prevalence among the Indian population, improved outcomes in HPV+ OPC patients and widely available IHC HPV assays signifies the routine implementation of p16 testing in day-to-day clinical practice.

Short Androgen Suppression and Radiation Dose Escalation in Prostate Cancer: 12-Year Results of EORTC Trial 22991 in Patients With Localized Intermediate-Risk Disease.

PURPOSE: The European Organisation for Research and Treatment of Cancer (EORTC) trial 22991 (NCT00021450) showed that 6 months of concomitant and adjuvant androgen suppression (AS) improves event- (EFS, Phoenix) and clinical disease-free survival (DFS) of intermediate- and high-risk localized prostatic carcinoma, treated by external-beam radiotherapy (EBRT) at 70-78 Gy. We report the long-term results in intermediate-risk patients treated with 74 or 78 Gy EBRT, as per current guidelines. PATIENT AND METHODS: Of 819 patients randomly assigned between EBRT or EBRT plus AS started on day 1 of EBRT, 481 entered with intermediate risk (International Union Against Cancer TNM 1997 cT1b-c or T2a with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≤ 7 and PSA ≤ 20 ng/mL, N0M0) and had EBRT planned at 74 (342 patients, 71.1%) or 78 Gy (139 patients, 28.9%). We report the trial primary end point EFS, DFS, distant metastasis-free survival (DMFS), and overall survival (OS) by intention-to-treat stratified by EBRT dose at two-sided α = 5%. RESULTS: At a median follow-up of 12.2 years, 92 of 245 patients and 132 of 236 had EFS events in the EBRT plus AS and EBRT arm, respectively, mostly PSA relapse (48.7%) or death (45.1%). EBRT plus AS improved EFS and DFS (hazard ratio [HR] = 0.53; CI, 0.41 to 0.70; P < .001 and HR = 0.67; CI, 0.49 to 0.90; P = .008). At 10 years, DMFS was 79.3% (CI, 73.4 to 84.0) with EBRT plus AS and 72.7% (CI, 66.2 to 78.2) with EBRT (HR = 0.74; CI, 0.53 to 1.02; P = .065). With 140 deaths (EBRT plus AS: 64; EBRT: 76), 10-year OS was 80.0% (CI, 74.1 to 84.7) with EBRT plus AS and 74.3% (CI, 67.8 to 79.7) with EBRT, but not statistically significantly different (HR = 0.74; CI, 0.53 to 1.04; P = .082). CONCLUSION: Six months of concomitant and adjuvant AS statistically significantly improves EFS and DFS in intermediate-risk prostatic carcinoma, treated by irradiation at 74 or 78 Gy. The effects on OS and DMFS did not reach statistical significance.