Cancer Control Rates Research Articles

Prostate high dose-rate brachytherapy as monotherapy for low and intermediate-risk prostate cancer: Efficacy results from a randomized phase II clinical trial of one fraction of 19 Gy or two fractions of 13.5 Gy: A 9-year update

Background and PurposeHigh dose-rate (HDR) brachytherapy as a monotherapy is an accepted treatment for localized prostate cancer, but the optimal dose and fractionation schedule remain unknown. We report on the efficacy of a randomized Phase II trial comparing HDR monotherapy delivered as 27 Gy in 2 fractions vs. 19 Gy in 1 fraction with a median follow-up of 9 years. Materials and MethodsEnrolled patients had low or intermediate-risk disease, <60 cc prostate volume and no androgen deprivation use. Patients were randomized to 27 Gy in 2 fractions delivered one week apart vs a single fraction of 19 Gy. Results170 patients were randomized: median age 65 years, median follow-up 107 months and median baseline PSA 6.35 ng/ml. NCCN risk categories comprised low (19 %), favourable (51 %), and unfavourable intermediate risk (30 %). The median PSA at 8 years was 0.08 ng/ml in the 2-fraction arm vs. 0.89 ng/ml in the single-fraction arm. The cumulative incidence of local failure at 8 years was 11.2 % in the 2-fraction arm vs. 35.9 % in the single-fraction arm (p < 0.001). The incidence of distant failure at 8 years was 3.8 % in the 2-fraction arm and 2.5 % in the single-fraction arm (p = 0.6). ConclusionsHDR monotherapy delivered in two fractions of 13.5 Gy demonstrated a persistent cancer control rate at 8 years and was well-tolerated. Single-fraction monotherapy yielded poor oncologic control and is not recommended. These findings contribute to the ongoing discourse on optimal HDR monotherapy strategies for low and intermediate-risk prostate cancer.

Qualitative Classification of Late Systemic Symptoms in Head and Neck Cancer Survivors.

Improved rates of cancer control have increased the head and neck cancer survivor population. Cancer survivorship clinics are not widely available in the USA, and longitudinal supportive care for patients undergoing multimodal therapy has not advanced at a pace commensurate with improvements in cancer control. Consequently, a large head and neck cancer survivor population whose quality of life may be chronically and/or permanently diminished presently exists. This lack of awareness perpetuates under-recognition and under-investigation, leaving survivors' (mostly detrimental) experiences largely uncharted. We conducted a qualitative exploration of survivors' experiences, aiming to unpack the profound impact of late systemic symptoms on daily life, encompassing work, relationships, and self-identity in the head and neck cancer survivor community. The study included 15 remitted head and neck survivors, ≥12 months from their final treatment, who participated in semi-structured interviews conducted by a medical oncologist. Data analysis comprised qualitative thematic analysis, specifically inductive hierarchical linear modeling, enriched by a deductive approach of anecdotal clinical reporting. Results highlighted that 43.36% of all quotation material discussed in the interviews pertained to chronic emotion disturbance with significant implications for other domains of life. A central symptom cluster comprised impairments in mood/emotions, daily activity, and significant fatigue. Dysfunction in sleep, other medical conditions, and cognitive deficits comprised a secondary cluster. Physical dysfunctionality, encompassing pain, appetite, and eating, and alterations in experienced body temperature, constituted a tertiary cluster, and perhaps were surprisingly the least discussed symptom burden among head and neck cancer survivors. Symptoms causing heightened long-term survivor burden may be considered epiphenomenal to central physical dysfunctionality, albeit being presently the least represented in cancer survivor care programs. Moving forward, the development of targeted and multi-dimensional treatment programs that encompass physical, psychosocial, and spiritual domains are needed to increase clinical specificity and effective holistic long-term solutions that will foster a more compassionate and informed future of care for the cancer survivorship community.

Synergistic Effect of Ginsenoside Rh2 Combines with Ionizing Radiation on CT26/luc Colon Carcinoma Cells and Tumor-Bearing Animal Model.

The local tumor control rate of colon cancer by radiotherapy is unsatisfactory due to recurrence and radioresistance. Ginsenoside Rh2 (Rh2), a panoxadiol saponin, possesses various antitumor effects. CT26/luc murine colon carcinoma cells and a CT26/luc tumor-bearing animal model were used to investigate the therapeutic efficacy of Rh2 combined with ionizing radiation and the underlying mechanisms. Rh2 caused cell cycle arrest at the G1 phase in CT26/luc cells; however, when combined with ionizing radiation, the cells were arrested at the G2/M phase. Rh2 was found to suppress the activity of NF-κB induced by radiation by inhibiting the MAPK pathway, consequently affecting the expression of effector proteins. In an in vivo study, the combination treatment significantly increased tumor growth delay time and overall survival. Furthermore, the combination treatment significantly reduced NF-κB and NF-κB-related effector proteins, along with PD-1 receptor expression. Additionally, Rh2 administration led to increased levels of interleukin-12, -18, and interferon-γ in the mice's sera. Importantly, biochemical analysis revealed no toxicities associated with Rh2 alone or combined with radiation. The combination of Rh2 with radiation may have potential as an alternative to improve the therapeutic efficacy of colorectal cancer.

The Role of Salvage Radical Prostatectomy in Patients with Radiation-Resistant Prostate Cancer.

There are multiple treatment strategies for patients with localized prostate adenocarcinoma. In intermediate- and high-risk patients, external beam radiation therapy demonstrates effective long-term cancer control rates comparable to radical prostatectomy. In patients who opt for initial radiotherapy but have a local recurrence of their cancer, there is no unanimity on the optimal salvage approach. The lack of randomized trials comparing surgery to other local salvage therapy or observation makes it difficult to ascertain the ideal management. A narrative review of existing prospective and retrospective data related to salvage radical prostatectomy after radiation therapy was undertaken. Based on retrospective and prospective data, post-radiation salvage radical prostatectomy confers oncologic benefits, with overall survival ranging from 84 to 95% at 5 years and from 52 to 77% at 10 years. Functional morbidity after salvage prostatectomy remains high, with rates of post-surgical incontinence and erectile dysfunction ranging from 21 to 93% and 28 to 100%, respectively. Factors associated with poor outcomes after post-radiation salvage prostatectomy include preoperative PSA, the Gleason score, post-prostatectomy staging, and nodal involvement. Salvage radical prostatectomy represents an effective treatment option for patients with biochemical recurrence after radiotherapy, although careful patient selection is important to optimize oncologic and functional outcomes.

Determinants of targeted cancer therapy use in community oncology practice: a qualitative study using the Theoretical Domains Framework and Rummler-Brache process mapping

BackgroundPrecision medicine holds enormous potential to improve outcomes for cancer patients, offering improved rates of cancer control and quality of life. Not all patients who could benefit from targeted cancer therapy receive it, and some who may not benefit do receive targeted therapy. We sought to comprehensively identify determinants of targeted therapy use among community oncology programs, where most cancer patients receive their care.MethodsGuided by the Theoretical Domains Framework, we conducted semi-structured interviews with 24 community cancer care providers and mapped targeted therapy delivery across 11 cancer care delivery teams using a Rummler-Brache diagram. Transcripts were coded to the framework using template analysis, and inductive coding was used to identify key behaviors. Coding was revised until a consensus was reached.ResultsIntention to deliver precision medicine was high across all participants interviewed, who also reported untenable knowledge demands. We identified distinctly different teams, processes, and determinants for (1) genomic test ordering and (2) delivery of targeted therapies. A key determinant of molecular testing was role alignment. The dominant expectation for oncologists to order and interpret genomic tests is at odds with their role as treatment decision-makers’ and pathologists’ typical role to stage tumors. Programs in which pathologists considered genomic test ordering as part of their staging responsibilities reported high and timely testing rates. Determinants of treatment delivery were contingent on resources and ability to offset delivery costs, which low- volume programs could not do. Rural programs faced additional treatment delivery challenges.ConclusionsWe identified novel determinants of targeted therapy delivery that potentially could be addressed through role re-alignment. Standardized, pathology-initiated genomic testing may prove fruitful in ensuring patients eligible for targeted therapy are identified, even if the care they need cannot be delivered at small and rural sites which may have distinct challenges in treatment delivery. Incorporating behavior specification and Rummler-Brache process mapping with determinant analysis may extend its usefulness beyond the identification of the need for contextual adaptation.

Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer (IMPORT HIGH): a multicentre, phase 3, non-inferiority, open-label, randomised controlled trial

A tumour-bed boost delivered after whole-breast radiotherapy increases local cancer-control rates but requires more patient visits and can increase breast hardness. IMPORT HIGH tested simultaneous integrated boost against sequential boost with the aim of reducing treatment duration while maintaining excellent local control and similar or reduced toxicity. IMPORT HIGH is a phase 3, non-inferiority, open-label, randomised controlled trial that recruited women after breast-conserving surgery for pT1-3pN0-3aM0 invasive carcinoma from radiotherapy and referral centres in the UK. Patients were randomly allocated to receive one of three treatments in a 1:1:1 ratio, with computer-generated random permuted blocks used to stratify patients by centre. The control group received 40 Gy in 15 fractions to the whole breast and 16 Gy in 8 fractions sequential photon tumour-bed boost. Test group 1 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 48 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. Test group 2 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 53 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. The boost clinical target volume was the clip-defined tumour bed. Patients and clinicians were not masked to treatment allocation. The primary endpoint was ipsilateral breast tumour relapse (IBTR) analysed by intention to treat; assuming 5% 5-year incidence with the control group, non-inferiority was predefined as 3% or less absolute excess in the test groups (upper limit of two-sided 95% CI). Adverse events were assessed by clinicians, patients, and photographs. This trial is registered with the ISRCTN registry, ISRCTN47437448, and is closed to new participants. Between March 4, 2009, and Sept 16, 2015, 2617 patients were recruited. 871 individuals were assigned to the control group, 874 to test group 1, and 872 to test group 2. Median boost clinical target volume was 13 cm3 (IQR 7 to 22). At a median follow-up of 74 months there were 76 IBTR events (20 for the control group, 21 for test group 1, and 35 for test group 2). 5-year IBTR incidence was 1·9% (95% CI 1·2 to 3·1) for the control group, 2·0% (1·2 to 3·2) for test group 1, and 3·2% (2·2 to 4·7) for test group 2. The estimated absolute differences versus the control group were 0·1% (-0·8 to 1·7) for test group 1 and 1·4% (0·03 to 3·8) for test group 2. The upper confidence limit for test group 1 versus the control group indicated non-inferiority for 48 Gy. Cumulative 5-year incidence of clinician-reported moderate or marked breast induration was 11·5% for the control group, 10·6% for test group 1 (p=0·40 vs control group), and 15·5% for test group 2 (p=0·015 vs control group). In all groups 5-year IBTR incidence was lower than the 5% originally expected regardless of boost sequencing. Dose-escalation is not advantageous. 5-year moderate or marked adverse event rates were low using small boost volumes. Simultaneous integrated boost in IMPORT HIGH was safe and reduced patient visits. Cancer Research UK.

Building Better Patient Care in Mississippi Radiation Oncology: Why Mississippi Needs a Collaborative Quality Initiative

Cancer is an insidious and devastating disease that affects many people. Progress in mortality rate has not been realized universally across the United States, and challenges remain in how to best make up the ground that has been lost in these areas, one of which is Mississippi. Radiation therapy is a significant contributor to cancer control rates and certain challenges exist specifically regarding this treatment modality. The challenges of radiation oncology in Mississippi have been reviewed and discussed, with the proposal of a potential collaboration between clinical practitioners and payors to provide optimal and cost-effective radiation therapy to patients in Mississippi. A similar model to that proposed has been reviewed and evaluated. This model is discussed based on its potential validity and usefulness in Mississippi. Significant barriers exist in the state of Mississippi to patients receiving a consistent standard of care, regardless of their location and socioeconomic status. A collaborative quality initiative has been shown to be a boon to this endeavor elsewhere and stands to have a similar impact in Mississippi.

The Emergence of Cancer Stem Cells in Early Diagnosed Prostate Cancer

The Emergence of Cancer Stem Cells in Early Diagnosed Prostate Cancer

Dose-Response Prediction for SBRT of Prostate Cancer Based on Measured Cell Survival Curves Using a Unified Multi-Activation Model

<h3>Purpose/Objective(s)</h3> Hypofractionated external beam radiotherapy with 10 to 30 fractions (fx) and stereotactic body radiation therapy (SBRT) for prostate cancer (PC) have similar rates of cancer control and toxicity at 5 years as compared to conventional treatment. There is a lack of a radiobiological modeling from lab experiments to guide this transition. By assuming a unified multi-activation (UMA) model of lab-measured radiosensitivity (RS) of the cell lines to the entire dose range, we explored the clinical dose-response, modeling tumor-control probability (TCP) and normal-tissue complication probability (NTCP). <h3>Materials/Methods</h3> Published cell survival curves (CSC) with experimental error bars for PC of 5 DU145 CSCs, 3 CP3 CSCs, 6 LNCaP + 2 LnCaP with BCL2 overexpressed or down-regulated CSCs, 3 wild-type (WT)-22RV1 CSCs, 3 post-radiation radioresistant (RR)-22RV1 CSCs, 2 hypoxia-22RV1 CSCs, 3 urothelial HCV-29 CSCs and 4 large intestine (LI) or small intestine (SI) stem cell and organoid CSCs were fitted with a UMA model by using a logit transformation and c²-regression to obtain the model parameters of g and n and their deviations. Cell survival at any fractional dose (=total dose/fx) and TCP and NTCP for the total number of cancer cells or normal tissue cells corresponding to a grade of toxicity were analytically determined from the parameters. <h3>Results</h3> All of the CSCs had been excellently fitted with R² > 0.95 and Q-factor > 0.2 excepting for two in-vivo LI/SI crypt CSCs each with an outline point. We identified radiobiological parameters and predicted TCP/NTCP curves and listed the data for the 8Gyx5 SBRT of PC in Table 1 that are comparable with the results listed in the HyTEC papers. The 0% TCP to RR or hypoxia PC and 100% NTCP to SI are similar to conventional EBRT. The Dg reflects the major uncertainties in the lab-measured RS. D50, the total dose at 50% TCP or NTCP, correlated with RS and number of cells. Cell heterogeneity greatly changed RS and shapes of TCP and NTCP curves. <h3>Conclusion</h3> These findings may be useful for the design and evaluation of new clinical treatment schemes in PC translating lab work into clinical application.

Gastric cancer incidence, mortality and burden in adolescents and young adults: a time-trend analysis and comparison among China, South Korea, Japan and the USA

ObjectivesTo evaluate and compare the burden of gastric cancer in adolescents and young adults (GCAYA) among China, South Korea, Japan and the USA, four countries with similar or different rates...

External beam and stereotactic radiation in the treatment of fibrolamellar carcinoma.

e16137 Background: Fibrolamellar Carcinoma (FLC) is an extremely rare (&lt; 50 cases/year US), distinct type of primary liver cancer, unrelated to hepatocellular carcinoma (HCC), affecting healthy children and young adults that often presents at an advanced stage. Surgery is the only known cure, but is only possible in half of patients, and, even with surgery, there is an 80% relapse rate. Loco-regional therapies can make surgery possible or replace surgery, allow systemic therapy time to work, and prolong life. However because of the paucity of data and the common misunderstanding of treating FLC as a “variant of hepatocellular carcinoma (HCC)” it is often assumed to be radio-resistant. For example, the 2021 NCCN Guidelines give no specific recommendations for radiation in FLC but classifying FLC as a “variant of HCC'' recommend 25 1.8Gy fractions (45Gy) with a boost to 50-60 Gy for external beam radiation(EBRT) and 3-5 10Gy fractions for stereotactic body radiation (SBRT). In their HCC reviews, the New England Journal of Medicine (2020), ASCO (2019), and the Fibrolamellar Cancer Summit (2017) do not discuss radiation. This is the largest collection of FLC patients treated with radiation in the literature to date and will hopefully inform clinicians of the option to use radiotherapy in this difficult to treat cancer. Methods: We reviewed the literature for cases of FLC treated with radiation after 2000. With IRB approval, (ORA#19071603), we collected data on all Rush FLC patients treated with radiation. Descriptive statistics were used to characterize this group of patients. Results: We found 29 instances of EBRT or SBRT treating FLC: 3 case reports, 21 of our patients (two had multiple (2 and 4) distinct treatments). Of these 24 (13F/10M/1 Unknown), median age at diagnosis/start of treatment 17(11-40)/23(13-45) underwent radiation with a median dose of 36 Gy (20-50). Ten of 27 were considered “palliative” treatments. High fraction therapy (&gt; 10 fractions) was used 9 times while low fraction therapy (≤ 10 fractions) 16. Biological Equivalent Dose median was 0.36108(0.2008-0.505). Six patients were treated concurrently with nivolumab. Mean prior systemic therapies was 2.6 (0-10) and 5 patients received prior radiation. Fourteen patients underwent SBRT, 10 conventional, 2 IMRT, and 2 unknown. Best response by RECIST 1.1 of the 27 instances with outcome data, was 21 CR, 2 PR, 2 PD, and 2 SD, for a objective response rate (CR + PR) of 85% and a cancer control rate (CR + PR + SD) of 93% at a median follow up of 13 months. In 18 out of 29 instances (62%), surgery was avoided after radiation. Late recurrence was noted in 2 out of 26 instances (8%). Conclusions: FLC is a rare disease lacking radiation guidelines. Our data strongly suggest radiotherapy can be effective with a variety of doses and strategies. We hope our report will encourage clinicians to consider EMRT/SBRT as part of a multi-modal approach to this difficult to treat cancer.

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review.

ABSTRACTPurpose:Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa.Material and methods:We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included.Results:Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade.Conclusions:This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

Focal prostate cancer therapy in the era of multiparametric MRI: a review of options and outcomes.

The goal of prostate cancer focal therapy is to achieve oncologic control while reducing the rate of adverse events associated with whole-gland treatments. Numerous focal therapy modalities are currently available with early data demonstrating highly variable rates of cancer control and preservation of sexual/urinary function. All English language clinical trial publications evaluating various focal therapies for localized prostate cancer were reviewed. The literature search was limited to studies from the modern era of MRI-guided treatment, as MRI is hypothesized to improve tumor localization and targeting. Primary outcomes were post-treatment cancer-free rates, in-field/out-of-field recurrence rates, and rates of conversion to radical therapy. Secondary outcomes were related to functional status and adverse events. Numerous focal therapies were identified with clinical data including high-intensity focused ultrasound, transurethral ultrasound ablation, focal laser ablation, focal cryotherapy, irreversible electroporation, and photodynamic therapy. Recurrence rates among all technologies were low to moderate (0-51%) and rates of freedom from radical treatment were highly variable (46-98%). Rates of erectile dysfunction and incontinence generally ranged from 0 to 44% and 0 to 12%, respectively, with variability between focal therapy modalities. Caution should be exercised when comparing studies as outcomes are strongly associated with patient selection. No individual focal therapy is currently recommended by society guidelines. Randomized controlled trials are ongoing in search of a standard of care. For localized MRI-visible prostate cancer, early clinical trial data demonstrate that focal therapy can provide good to moderate cancer control while having preferable side effect profiles compared to whole-gland treatments. While current studies do not make head-to-head comparisons between technologies, early data suggest a potential for these technologies to provide adequate cancer control in a well-selected patient population. The oncologic outcomes of some focal therapies appear promising; however, longer-term follow-up data are needed to assess the durability of early outcomes.

Long-Term Outcomes of a Phase I Trial of Weekly Docetaxel, Total Androgen Blockade, and Image-Guided Intensity-Modulated Radiotherapy for Localized High-Risk Prostate Adenocarcinoma

<h3>Purpose/Objective(s)</h3> In high-risk localized prostate cancer (HRLPC), the standard of care is dose-escalated radiation therapy (DERT) with long-term androgen deprivation therapy (LTADT). Unfortunately, outcomes are less than ideal. There is significant interest in improving outcomes by intensifying treatment for these patients using docetaxel (D). This phase I study was designed to find the maximum tolerable dose (MTD) of concurrent weekly D when combined with DERT to the prostate with long-term androgen deprivation therapy (LTADT) in HRLPC patients. Initial results reported demonstrated a MTD for docetaxel of 25 mg/m² with acceptable toxicities. Here we describe the long-term outcomes in these patients. <h3>Materials/Methods</h3> We enrolled 19 patients with HRLPC (≥1 of ≥cT2c, PSA ≥20ng/ml, or Gleason ≥8) on this phase 1 study. Patients received neoadjuvant combined androgen blockade for 2 months and then during radiation of 77.4 Gy to the prostate and 45 Gy to the seminal vesicles with concurrent weekly D. No pelvic/nodal radiotherapy was given. D was administered in a standard dose-escalated scheme requiring ≥3 patients per cohort, starting at 10mg/m² and increasing to 30mg/m² in 5mg/m² increments. The GnRH agonist was continued for an additional 24 months. The primary objective of the study was to determine the MTD of D in combination with DERT and LTADT. Secondary end points included progression free survival (PFS), metastasis free survival (MFS) and overall survival (OS). Kaplan-Meier analysis was used to estimate the survival probabilities. <h3>Results</h3> MTD was found to be 25mg/m². There was no grade ≥3 toxicity at this or lower dose levels. At a median follow up of 10.5 years the median OS was not reached. 5-year and 10-year OS was found to be 89.5% and 68.4%, respectively. Median MFS was found to be 11.3 years with 5- and 10-year MFS of 84.2% and 57.9%. Median PFS was 9.0 years with 73.7% and 42.1% at 5 and 10 years, respectively. <h3>Conclusion</h3> In the setting of high-dose IMRT to the prostate with concurrent LTADT the MTD of concurrent weekly docetaxel is 25mg/m². This study showed a 5-year OS of 89.5% with a median OS not reached with > 10 years of follow-up. This mature data suggests that the addition of concurrent weekly docetaxel at 25mg/m² to high-dose IMRT to the prostate is safe and may provide cancer control rates similar to those recently reported for adjuvant full-dose D.

Heterogeneity in Radiotherapeutic Parameter Assumptions in Cost-Effectiveness Analyses in Prostate Cancer: A Call for Uniformity

ObjectivesCost-effectiveness analyses (CEAs) may provide useful data to inform management decisions depending on the robustness of a model’s input parameters. We sought to determine the level of heterogeneity in health state utility values, transition probabilities, and cost estimates across published CEAs assessing primarily radiotherapeutic management strategies in prostate cancer. MethodsWe conducted a systematic review of prostate cancer CEAs indexed in MEDLINE between 2000 and 2018 comparing accepted treatment modalities across all cancer stages. Search terms included “cost effectiveness prostate,” “prostate cancer cost model,” “cost utility prostate,” and “Markov AND prostate AND (cancer OR adenocarcinoma).” Included studies were agreed upon. A Markov model was designed using the parameter estimates from the systematic review to evaluate the effect of estimate heterogeneity on strategy cost acceptability. ResultsOf 199 abstracts identified, 47 publications were reviewed and 37 were included; 508 model estimates were compared. Estimates varied widely across variables, including gastrointestinal toxicity risk (0%-49.5%), utility of metastatic disease (0.25-0.855), intensity-modulated radiotherapy cost ($21 193-$61 996), and recurrence after external-beam radiotherapy (1.5%-59%). Multiple studies assumed that different radiotherapy modalities delivering the same dose yielded varying cancer control rates. When using base estimates for similar parameters from included studies, the designed model resulted in 3 separate acceptability determinations. ConclusionsSignificant heterogeneity exists across parameter estimates used to perform CEAs evaluating treatment for prostate cancer. Heterogeneity across model inputs yields variable conclusions with respect to the favorability and cost-effectiveness of treatment options. Decision makers are cautioned to review estimates in CEAs to ensure they are up to date and relevant to setting and population.

The efficacy and safety of bevacizumab combined with FOLFOX regimen in the treatment of advanced colorectal cancer: A systematic review and meta-analysis.

Background:It is necessary to systematically evaluate the clinical efficacy and safety of bevacizumab (BEV) combined with 5-fluorouracil + leucovorin + oxaliplatin (FOLFOX) regimen in the treatment of advanced colorectal cancer.Methods:We searched the PubMed et al databases for randomized controlled trials (RCTs) on the BEV combined with the FOLFOX regimen in the treatment of advanced colorectal cancer up to January 20, 2021. The Cochrane Collaborations’ risk of bias tool was used for the quality assessment of included RCTs. Revman5.3 software was used for meta-analysis.Results:Eleven RCTs with a total of 3178 patients with advanced colorectal cancer were included, meta-analysis results showed that the objective response rate (odds ratio [OR] = 3.15, 95% confidence intervals [CI]: 2.25–4.40, P < .001) and cancer control rate (OR = 2.73, 95% CI: 1.91–3.90, P < .001) of BEV + FOLFOX were higher than that of FOLFOX group. And the incidence of gastrointestinal adverse reactions (OR = 1.29, 95% CI: 1.07–1.55, P = .008) in the BEV + FOLFOX group was higher than that of the FOLFOX group, there were no significant differences in the incidence of leukopenia (OR = 1.04, 95% CI: 0.72–1.50, P = .83), hypertension (OR = 3.92, 95% CI: 0.81–18.88, P = .09) and neurotoxicity (OR = 1.00, 95% CI: 0.8–1.27, P = .98) between the 2 groups.Conclusion:BEV combined with the FOLFOX regimen is more effective than the FOLFOX regimen alone in the treatment of advanced colorectal cancer, but it may also increase the risk of gastrointestinal adverse reactions.

Collagen metabolism as a regulator of proline dehydrogenase/proline oxidase-dependent apoptosis/autophagy

Recent studies on the regulatory role of amino acids in cell metabolism have focused on the functional significance of proline degradation. The process is catalysed by proline dehydrogenase/proline oxidase (PRODH/POX), a mitochondrial flavin-dependent enzyme converting proline into ∆1-pyrroline-5-carboxylate (P5C). During this process, electrons are transferred to electron transport chain producing ATP for survival or they directly reduce oxygen, producing reactive oxygen species (ROS) inducing apoptosis/autophagy. However, the mechanism for switching survival/apoptosis mode is unknown. Although PRODH/POX activity and energetic metabolism were suggested as an underlying mechanism for the survival/apoptosis switch, proline availability for this enzyme is also important. Proline availability is regulated by prolidase (proline supporting enzyme), collagen biosynthesis (proline utilizing process) and proline synthesis from glutamine, glutamate, α-ketoglutarate (α-KG) and ornithine. Proline availability is dependent on the rate of glycolysis, TCA and urea cycles, proline metabolism, collagen biosynthesis and its degradation. It is well established that proline synthesis enzymes, P5C synthetase and P5C reductase as well as collagen prolyl hydroxylases are up-regulated in most of cancer types and control rates of collagen biosynthesis. Up-regulation of collagen prolyl hydroxylase and its exhaustion of ascorbate and α-KG may compete with DNA and histone demethylases (that require the same cofactors) to influence metabolic epigenetics. This knowledge led us to hypothesize that up-regulation of prolidase and PRODH/POX with inhibition of collagen biosynthesis may represent potential pharmacotherapeutic approach to induce apoptosis or autophagic death in cancer cells. These aspects of proline metabolism are discussed in the review as an approach to understand complex regulatory mechanisms driving PRODH/POX-dependent apoptosis/survival.

SEMS trial: Result of a prospective, multi-institutional phase II clinical trial of surgery in early metastatic seminoma.

375 Background: Chemotherapy or radiotherapy are standard treatments for stage II seminoma, though they are associated with significant long-term treatment-related toxicities. Retroperitoneal lymph node dissection (RPLND) is an established treatment for testicular germ cell tumors but little data exists on its efficacy as a front-line treatment in early metastatic (stage II) seminoma. This is a single-arm, multi-institutional (NCT02537548), phase II study of retroperitoneal lymph node dissection (RLND) as first-line treatment for testicular seminoma with isolated retroperitoneal disease. Methods: Twelve sites in the United States and Canada prospectively enrolled patients (16 years of age) with testicular seminoma and isolated retroperitoneal lymphadenopathy between 1-3 cm in size. Patients were excluded if they received prior therapy (except orchiectomy) for testicular cancer. Open, modified-template RPLND was performed by qualified surgeons with a primary endpoint of 2-year recurrence-free survival. Data on complication rates (short and long-term), pathologic up/downstaging, recurrence patterns, adjuvant therapies, and treatment-free survival were assessed. Results: A total of 55 patients were enrolled and underwent RPLND. Fourteen patients had initial stage I disease who developed isolated retroperitoneal relapse while 41 patients had clinical stage IIA-B at presentation. With a median follow-up of 24 months (8-52 months), there were a total of 10 recurrences. The overall recurrence rate was 18% with a median time to recurrence of 8 months. Of the recurrences, 8 underwent chemotherapy (6 BEP X 3, 1 EP X 4, 1 carbo/etoposide) and 2 underwent additional surgery. The two-year recurrence free survival was 87% and the overall survival was 100%. There were 7 (13%) patients who experienced short-term complications within 1 year of RPLND. Of these, 5 (9%) were classified as Clavien Dindo I-II and 2 (3.6%) were classified as Clavien Dindo III. No patients have reported long-term complications. Conclusions: This trial establishes RPLND as a therapeutic option as a first-line treatment in early metastatic seminoma. The surgery offers cancer control rates similar to those seen in non-seminomatous germ cell tumors. Clinical trial information: NCT02537548.

Recommendations on robotic-assisted radical prostatectomy: a Brazilian experts' consensus.

Radical prostatectomy is a commonly adopted treatment for localized/locally advanced prostate cancer in men with a life expectancy of ten years or more. Robotic-assisted radical prostatectomy (RARP) is comparable to open radical prostatectomy on cancer control and complication rates; however, new evidence suggests that RARP may have better functional outcomes, especially with respect to urinary incontinence and erectile dysfunction. Some of the surgical steps of RARP are not adequately described in published literature and, as such, may have an impact on the final outcomes of the procedure. We organized a Brazilian experts' panel to evaluate best practices in RARP. The confection of the recommendations broadly involved: selection of the experts; establishment of working groups; systematic review of the literature and elaboration of a questionnaire; and construction of the final text with the approval of all participants. The participants reviewed the publications in English from December 2019 to February 2020. A one-round Delphi technique was employed in 188 questions. Five reviewers worked on the final recommendations using consensual and non-consensual questions. We found 59.9% of questions with greater than 70% agreement that were considered consensual. Non-consensual questions were reported according to the responses. The recommendations were based on evidence-based literature and individual perceptions adapted to the Brazilian reality, although some issues remain controversial. We believe that these recommendations may help urologists involved in RARP and hope that future discussions on this surgical procedure may evolve over the ensuing years.

MP67-08 SALVAGE ROBOT ASSISTED RADICAL PROSTATECTOMY VS SALVAGE RE-IRRADIATION FOR PATIENT WITH RADIO-RECURRENT PROSTATE CANCER AFTER PRIMARY RADIOTHERAPY: ONCOLOGICAL OUTCOMES

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy III (MP67)1 Apr 2020MP67-08 SALVAGE ROBOT ASSISTED RADICAL PROSTATECTOMY VS SALVAGE RE-IRRADIATION FOR PATIENT WITH RADIO-RECURRENT PROSTATE CANCER AFTER PRIMARY RADIOTHERAPY: ONCOLOGICAL OUTCOMES Damiano Vizziello*, Ettore Di Trapani, Dario Zerini, Damaris Patricia Rojas, Francesco Alessandro Mistretta, Stefano Luzzago, Giulia Marvaso, Andrea Conti, Giulia Garelli, Giovanni Cordima, Giuseppe Petralia, Matteo Ferro, Victor Deliu Matei, Barbara Alicja Jereczek, Gennaro Musi, and Ottavio de Cobelli Damiano Vizziello*Damiano Vizziello* More articles by this author , Ettore Di TrapaniEttore Di Trapani More articles by this author , Dario ZeriniDario Zerini More articles by this author , Damaris Patricia RojasDamaris Patricia Rojas More articles by this author , Francesco Alessandro MistrettaFrancesco Alessandro Mistretta More articles by this author , Stefano LuzzagoStefano Luzzago More articles by this author , Giulia MarvasoGiulia Marvaso More articles by this author , Andrea ContiAndrea Conti More articles by this author , Giulia GarelliGiulia Garelli More articles by this author , Giovanni CordimaGiovanni Cordima More articles by this author , Giuseppe PetraliaGiuseppe Petralia More articles by this author , Matteo FerroMatteo Ferro More articles by this author , Victor Deliu MateiVictor Deliu Matei More articles by this author , Barbara Alicja JereczekBarbara Alicja Jereczek More articles by this author , Gennaro MusiGennaro Musi More articles by this author , and Ottavio de CobelliOttavio de Cobelli More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000947.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To compare oncological outcomes after salvage Robot Assisted Radical Prostatectomy (S-RARP) or salvage re-irradiation (S-RT) in patients with radiation-recurrent prostate cancer (rrPCa) after primary external beam radiation therapy (EBRT) or brachytherapy (BT). METHODS: We retrospective identified 74 patients with rrPCa (2010-2016). Of those, 54 (73 %) vs. 20 (27 %) were previously treated with EBRT vs. BT. All patients with rrPCa were diagnosed with PSA raising and choline PET (showing non-metastatic disease), or multiparametric MRI followed by prostate biopsy in both groups. Overall, 29 (40%) vs. 45 (60%) patients were treated with S-RARP vs. S-RT. All S-RARP were non Nerve Sparing with extended bilateral pelvic limph node dissection, while S-RT patients underwent intensity modulated or stereotactic radiation therapy on the prostate with a 25 to 30 Gy dose divided in 5 to 6 fractions. Kaplan-Meier plots depicted progression free (PFS), cancer-specific (CSS) and overall (OS) rates over time in S-RARP vs. S-RT patients. The cut off for Biochemical Relapse (BCR) after S-RT was assessed as PSA nadir after RT + 2 ng/ml, according to the Philadelphia criteria, while for S-RARP was 0,1 ng/ml. RESULTS: Compared to S-RARP, patients treated with S-RT were older (75.8 vs. 67 years; p=0.001). Overall, 16 (55%) vs. 23 (52%) and 13 (45%) vs. 22 (48%) patients treated with S-RARP vs. S-RT had a primary diagnosis of ISUP GG1 and ISUP GG 2 PCa before primary RT (p=0.7). Median time from primary RT to salvage treatment was, respectively, 65.5 (IQR 26.55 - 90.15) vs 102.6 (IQR 78.4 – 130.6) months for S-RARP vs S-RT (P= 0.001). Median time follow-up after salvage treatment was 41.5 months. Overall, 11 (39.3%) vs. 22 (56.4%) patients had biochemical recurrence after S-RARP vs. S-RT (p=0.1). Moreover, CSM and OCM rates were, respectively, 0(0 %) vs. 6 (13 %) (p=0,04) and 0 (0 %) vs. 6 (13 %) (p= 0,04) in patients treated with S-RARP vs. S-RT. CONCLUSIONS: S-RARP and S-RT appears to achieve the same rates of cancer control in patient swith radio-recurrent prostate cancer after primary RT. Despite this, randomized control trials are needed to confirm these results. Source of Funding: none. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1028-e1028 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Damiano Vizziello* More articles by this author Ettore Di Trapani More articles by this author Dario Zerini More articles by this author Damaris Patricia Rojas More articles by this author Francesco Alessandro Mistretta More articles by this author Stefano Luzzago More articles by this author Giulia Marvaso More articles by this author Andrea Conti More articles by this author Giulia Garelli More articles by this author Giovanni Cordima More articles by this author Giuseppe Petralia More articles by this author Matteo Ferro More articles by this author Victor Deliu Matei More articles by this author Barbara Alicja Jereczek More articles by this author Gennaro Musi More articles by this author Ottavio de Cobelli More articles by this author Expand All Advertisement PDF downloadLoading ...