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Context: Salvage radiotherapy may potentially cure patients with disease recurrence after radical prostatectomy, but previous evidence has suggested that it is ineffective in patients at the highest risk of metastatic disease progression. Objective: To delineate patients who may benefit from salvage radiotherapy for prostate cancer recurrence by identifying variables associated with a durable response. Design, Setting, and Patients: Retrospective review of a cohort of 501 patients at 5 US academic tertiary referral centers who received salvage radiotherapy between June 1987 and November 2002 for detectable and increasing prostate-specific antigen (PSA) levels after radical prostatectomy. Main outcome measure: Disease progression after salvage radiotherapy, defined as a serum PSA value ⩾0.1 ng/mL above the postradiotherapy PSA nadir confirmed by a second PSA measurement that was higher than the first by any amount, by a continued increase in PSA level after treatment, or by the initiation of androgen deprivation therapy after treatment. Results: Over a median follow-up of 45 months, 250 patients (50%) experienced disease progression after treatment, 49 (10%) developed distant metastases, 20 (4%) died from prostate cancer, and 21 (4%) died from other or unknown causes. The 4-year progression-free probability (PFP) was 45% (95% confidence interval [CI], 40%–50%). By multivariable analysis, predictors of progression were Gleason score of 8 to 10 (hazard ratio [HR], 2.6; 95% CI, 1.7–4.1; P < .001), preradiotherapy PSA level greater than 2.0 ng/mL (HR, 2.3; 95% CI, 1.7–3.2; P < .001), negative surgical margins (HR, 1.9; 95% CI, 1.4–2.5; P < .001), PSA doubling time (PSADT) of 10 months or less (HR, 1.7; 95% CI, 1.2–2.2; P = .001), and seminal vesicle invasion (HR, 1.4; 95% CI, 1.1–1.9; P = .02). Patients with no adverse features had a 4-year PFP of 77% (95% CI, 64%–91%). When treatment was given for early recurrence (PSA level ⩽2.0 ng/mL), patients with Gleason scores of 4 to 7 and a rapid PSADT had a 4-year PFP of 64% (95% CI, 51%–76%) and of 22% (95% CI, 6%–38%) when the surgical margins were positive and negative, respectively. Patients with Gleason scores of 8 to 10, positive margins, and receiving early salvage radiotherapy had a 4-year PFP of 81% (95% CI, 57%–100%) when the PSADT was longer than 10 months and of 37% (95% CI, 16%–58%) when the PSADT was 10 months or less. Conclusions: Gleason score, preradiotherapy PSA level, surgical margins, PSADT, and seminal vesicle invasion are prognostic variables for a durable response to salvage radiotherapy. Selected patients with high-grade disease and/or a rapid PSADT who were previously thought to be destined to develop progressive metastatic disease may achieve a durable response to salvage radiotherapy. [Copyright &y& Elsevier]

Purpose: To investigate the performance of a model‐based optimization process for volumetric modulated arc therapy (VMAT) applied to prostate cancer patients with the multi‐planner. Methods and Materials: The 120 prostate plans for VMAT treatment were entered into the database system of the RapidPlan (RP) knowledge‐based treatment planning. The treatment planning data for each plan was used to create and train the RP model. Twelve prostate cancer cases were selected and were used for planning by a manual of 12 planners based on the clinical protocol for dose constraints. Then, the treatment plans for each patient were compared with the RP model plans and analyzed with Wilcoxon tests. Results: On average, the RP models can estimate comparable doses among all planner plans and clinical plans for the PTV, which Dmax, D95%, D98%, HI, and CI were used to evaluate. For the normal organ doses of the bladder, rectum, penile bulb, and femoral head, all RP model plans showed comparable or better dose sparing than all planner plans and clinical plans. Moreover, the average planning time of the RP model was faster than manual plans by about two times. The RP model can significantly reduce the variation dose of the normal organs compared with the manual plans among the planners. Conclusion: The automated plans of the RP model might benefit from further fine‐tuning of the dose constraints of the normal organs, although both procedure plans are acceptable and fulfill the clinical protocol goals so that the RP model can enhance the efficacy and quality of plans. [ABSTRACT FROM AUTHOR]

Background: Over the years, radiotherapy has been established as a tool to improve local control for high-grade sarcomas. Although the European Society for Medical Oncology guidelines has taken notice of a shift toward a neoadjuvant radiotherapy approach, the American Society for Radiation Oncology guidelines clearly favor a neoadjuvant approach, citing debilitating long-term adverse effects when radiotherapy is applied postoperatively. In this study, we examined these irradiation-associated adverse events for adjuvant radiotherapy and focused on the prognostic factors for disease outcome, including local control. Methods: In this retrospective study, data for 106 patients with extremity soft-tissue sarcomas diagnosed between 1997 and 2021, of which 40 received adjuvant radiotherapy, were collected from the clinical and radiological information systems of a high-volume sarcoma treatment center. These data were then analyzed for radiation-associated side effects as well as predictive factors for overall survival, disease-free survival, local control, and surgical complications. Results: Radiotherapy was beneficial to patients improving local control, especially for high-grade sarcomas, even when those were resected with negative margins. Side effects due to radiotherapy occurred in 87.5% of the patients, and these effects primarily included radiation dermatitis in 67.5%; however, only 40.0% had any adverse event of ≥ grade 2 according to Common Terminology Criteria for Adverse Events. Long-term function-limiting side effects occurred in 45.0% of the patients; 10% exhibited ≥ grade 2 function-limiting adverse events. Greater time between surgery and adjuvant radiotherapy was beneficial for the patients, whereas joint infiltrating sarcomas were associated with more severe long term, function-limiting adverse events. 28.3% of the patients experienced a recurrence at any location (median time 18.35 months) and in 16% the recurrence was local (median time 16.11 months), resulting in 1, 3, and 5 year disease-free survival rates of 74.1, 58.9, and 38.5% and local control rates of 78.7, 61.6, and 42.8% were observed, respectively. Conclusion: Recurrences may be avoided with high-dose radiation, especially for high-grade G2 and G3 sarcomas, even after complete R0 resection. This resulted in a low rate of severe long-term function-limiting adverse events. Thus, adjuvant radiotherapy should be seriously considered when planning patient treatment, especially when treating patients that present with high-grade sarcomas. [ABSTRACT FROM AUTHOR]

Cancer is a major medical problem worldwide. Due to its high heterogeneity, the use of the same drugs or surgical methods in patients with the same tumor may have different curative effects, leading to the need for more accurate treatment methods for tumors and personalized treatments for patients. The precise treatment of tumors is essential, which renders obtaining an in-depth understanding of the changes that tumors undergo urgent, including changes in their genes, proteins and cancer cell phenotypes, in order to develop targeted treatment strategies for patients. Artificial intelligence (AI) based on big data can extract the hidden patterns, important information, and corresponding knowledge behind the enormous amount of data. For example, the ML and deep learning of subsets of AI can be used to mine the deep-level information in genomics, transcriptomics, proteomics, radiomics, digital pathological images, and other data, which can make clinicians synthetically and comprehensively understand tumors. In addition, AI can find new biomarkers from data to assist tumor screening, detection, diagnosis, treatment and prognosis prediction, so as to providing the best treatment for individual patients and improving their clinical outcomes. [ABSTRACT FROM AUTHOR]

Background/Aim: Dosimetric parameters in volumetric modulated arc therapy (VMAT), non-coplanar VMAT (NC-VMAT), and automated NC-VMAT (HyperArc, HA) were compared for patients with maxillary sinus carcinoma (MSC). Patients and Methods: Twenty HA plans were generated to deliver 70.4, 64, and 46 Gy for planning target volumes with high (PTV1), intermediate (PTV2), and low risk (PTV3), respectively. The VMAT and NC-VMAT plans were retrospectively generated using the same optimized parameters as those used in the HA plans. Results: For PTV1, the three treatment plans provided comparable target coverages. For PTV2, the D95%, D99%, and Dmin in the HA plans (64.7±1.2, 62.7±2.1 and 54.6±6.2 Gy, respectively) were significantly higher (p<0.05) than those in the VMAT plans (64.3±1.7, 61.9±2.4 and 52.9±6.4 Gy, respectively). The NC-VMAT and HA plans provided significantly higher (p<0.05) dosimetric parameters for PTV3 than those in the VMAT plans, and D99% in the HA was significantly higher than that in the NC-VMAT plans (52.5±3.0 vs. 51.8±2.7 Gy, p<0.05). The doses to the brain and brainstem were lowest in the HA plans (p<0.05). Moreover, dosimetric parameters of the contralateral organs (lens, optic nerve, retina, and parotid) were lower in the HA plans than in the VMAT and NC-VMAT plans. Conclusion: The HA plans provided the best target coverage and OAR sparing compared with VMAT and NC-VMAT plans for patients with MSC. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the value of [68Ga]Ga-labelled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) in the initial staging of patients with newly diagnosed nasopharyngeal carcinoma (NPC), compared with 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) PET/CT. Materials and Methods: Forty-seven treatment-naïve patients with newly diagnosed NPC underwent magnetic resonance imaging (MRI), [68Ga]Ga-DOTA-FAPI-04 PET/CT and [18F]F-FDG PET/CT within 1 week. The diagnostic efficiency of all imaging modalities for evaluating primary tumour extension was compared from the two aspects of soft tissue and bony structure involvement. The accuracy of two PET/CT methods for diagnosing cervical lymph node (CLN) metastases was compared, and MRI served as the standard reference. T and N stages were assessed by MRI, [68Ga]Ga-FAPI PET/CT and [18F]F-FDG PET/CT. Immunohistochemical (IHC) staining for FAP was conducted in 22 of the patients. Results: [68Ga]Ga-FAPI PET/CT outperformed [18F]F-FDG PET/CT in the assessment of primary tumour invasion in the cavernous sinus (10 vs. 1, p < 0.001) and bony structures (207 vs. 177, p < 0.001). Compared with MRI, [68Ga]Ga-FAPI PET/CT upgraded and underestimated T stage in 13 and 2 patients, while [18F]F-FDG PET/CT upgraded and underestimated T stage in 5 and 13 patients. However, [68Ga]Ga-FAPI PET/CT was inferior to [18F]F-FDG PET/CT in diagnosing positive CLNs based on the analyses of patients, neck sides, neck levels and individual nodes. [68Ga]Ga-FAPI PET/CT changed therapeutic schedules in 8 patients because of stage group changes. The presence of FAP with high quantity and intensity in cancer-associated fibroblasts (CAFs) was confirmed in all tumour specimens. Conclusion: [68Ga]Ga-FAPI PET/CT outperformed [18F]F-FDG PET/CT in detecting the cavernous sinus and bony structure involvement of primary NPC tumours, suggesting its value in improving T staging and therapeutic regimen selection. However, the performance of [68Ga]Ga-FAPI PET/CT is less promising for N staging because it detected fewer positive CLNs than [18F]F-FDG PET/CT. [ABSTRACT FROM AUTHOR]

In this review, we attempt to make a case for the establishment of a limited number of heavy ion cancer research and treatment facilities in the United States. Based on the basic physics and biology research, conducted largely in Japan and Germany, and early phase clinical trials involving a relatively small number of patients, we believe that heavy ions have a considerably greater potential to enhance the therapeutic ratio for many cancer types compared to conventional X-ray and proton radiotherapy. Moreover, with ongoing technological developments and with research in physical, biological, immunological, and clinical aspects, it is quite plausible that cost effectiveness of radiotherapy with heavier ions can be substantially improved. [ABSTRACT FROM AUTHOR]

Purpose: The prevalence of erectile dysfunction (ED) and the utilization of inflatable penile prosthesis (IPP) among prostate cancer patients are understudied. The aim of the study was to examine the relationships between ED, prostate cancer treatment type and IPP implantation in a national cohort. Materials and Methods: We identified a retrospective cohort of Surveillance, Epidemiology, and End Results (SEER)-Medicare patients diagnosed with locoregional prostate cancer between 2006 and 2011 and treated with surgery or radiation. Chi-square tests were used to detect significant differences in ED rates as well as use of IPP among the subset with ED. Multivariable logistic regression was used to examine factors associated with the use of IPP. Results: Among 31,233 patients in our cohort, 10,334 (33.1%) received prostatectomy and 20,899 (66.9%) received radiation. ED within 5 years was significantly more common in the prostatectomy group relative to those the radiation group (65.3% vs. 33.8%, p<0.001). In the subset of 13,812 patients with ED, the radiation group had greater median time to ED diagnosis compared to the prostatectomy group (346 vs. 133 days, p<0.001). IPP implantation was more frequent for prostatectomy patients than for radiation patients (3.6% vs. 1.4%, p<0.001). Cancer treatment type, race, and marital status were significantly associated with IPP utilization. Conclusions: ED is highly prevalent among prostate cancer patients, and IPP implantation is be underutilized. ED rates, time to ED diagnosis and utilization of IPP differed significantly by prostate cancer treatment type. [ABSTRACT FROM AUTHOR]

To determine morphological and biological control as well as toxicity and quality of life (QoL) of men with localized prostate cancer (PCa) treated with MRI-guided focal boost radiotherapy. 30 patients with PCa and a visible dominant intraprostatic lesion (DIL) identified on mpMRI were included in a prospective Phase II trial. Matching point registration of planning CT and T2W, diffusion-weighted and a gradient-recalled echo (GRE) MRI images made in treatment position was used for prostate and tumour delineation. Treatment consisted on 35 daily fractions of 2.17 Gy with a concomitant focal boost to the DIL of 2.43 Gy using volumetric modulated arc therapy (VMAT) and image-guided radiation therapy (IGRT) with intraprostatic fiducial markers. Biochemical failure was analysed using PSA nadir +2 ng/mL criteria and local control using mpMRI evaluation at 6–9 months following RT. Acute and late toxicity were defined according to CTCAE v.4.0 and RTOG/EORTC scales and QoL was assessed using IPSS, EPIC short-form and UCLA-PCI questionnaires. The median radiation dose to the prostate was 77.6 Gy (IQR 77.3–78.1), and to the DIL was 85.5 Gy (IQR 85.0–86.0). With a median follow up of 30.0 months (IQR 25.5–40.27), all patients remain free of biochemical relapse. An mpMRI complete response was observed in 25 patients during the first post-treatment evaluation at 6 months. The remaining five patients achieved a complete disappearance of the DIL both on T2 and DWI on the second mpMRI performed at 9 months following treatment. Six out of 30 (20%) patients presented acute Grade 2 urinary toxicity with no Grade 3 acute complications. Acute rectal toxicity was only found in 2 (6.6%) patients (both Grade 1). Only late Grade 1 urinary and rectal complications were observed in 3/30 patients, respectively, with no Grade 2 or more late toxicity. The urinary, bowel and sexual bother EPIC scores were slightly and insignificantly increased in the first 3 months post-treatment, returning to normal afterwards. mpMRI-guided focal boost using VMAT hypofractionated technique is associated with an excellent morphological and functional response control and a safe toxicity profile. In the present trial, we examined the potential role of mpMRI for radiological assessment (functional and morphological) of treatment response in high-risk prostate cancer patients treated with MRI-guided focal radiotherapy dose intensification to dominant Intraprostatic lesion. [ABSTRACT FROM AUTHOR]

3D - Conformal Radiotherapy (3DCRT) for decades was a standard technique in the prostate cancer radical radiotherapy treatment. Technological advances and implementation of an innovative radiotherapy technique-Intensity Modulated Radiation Therapy (IMRT), enable even more precise treatment of the prostate cancer patients. Intensity Modulated Radiation Therapy (IMRT) is a technological advancement in Conformal Radiotherapy which allows superior conformity and homogeneity of the absorbed dose in planning target volume with maximal sparing organs of risk. This technique gives us possibility to escalate the radiotherapy dose, prerequisite for the adequate local tumor control. Evaluation of dosimetric parameters 3DCRT vs. IMRT: the homogeneity index, the conformity index, parameters of absorbed dose in planning target volume, dose volume constraints for organs of risk shows that IMRT is an optimal technique in the prostate cancer radical treatment. [ABSTRACT FROM AUTHOR]

Background To investigate the feasibility of dose escalation (86Gy at 2Gy/fraction) with intensity modulated radiation therapy (IMRT) in intermediate-risk prostate cancer without androgen deprivation therapy. Methods Patients with histologically proven adenocarcinoma of the prostate, intermediate prognostic category, were enrolled in this study. Early and late toxicity were scored according to the Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 3.0. Treatment outcome was stated in terms of biochemical failure, biopsy result and clinical failure. Results 39 patients with a median followup of 71 months were analyzed. No patient experienced G3 or G4 acute gastrointestinal (GI) or genitourinary (GU) toxicity. G2 acute GI and GU toxicity were observed in 17 (44%) and 20 (51%) patients, respectively. Fourteen patients (36%) did not experience acute GI toxicity and 4 patients (10%) did not experience acute GU toxicity. G2 late GI bleeding occurred in 7 of 39 patients (18%). Both G3 and G4 late GI toxicity were seen only in one patient (2.5%). Two patients (5%) experienced G2 late GU toxicity, while G3 late GU toxicity occurred in 3 patients (8%). The 5-year actuarial freedom from biochemical failure (FFBF) was 87%. Thirty-four patients (87%) did not show biochemical relapse. Seventeen patients (44%) underwent biopsy two year after radiotherapy; of these only two were non-negative and both did not show evidence of biochemical disease. Conclusions IMRT treatment of patients with localized intermediate-risk prostate cancer at high dose levels without using androgen deprivation therapy (ADT) seems to give good disease control. Nevertheless, future trials should aim at further decreasing toxicity by exploiting image guidance techniques and by reducing the dose delivered at the interface between organs at risk and prostate. [ABSTRACT FROM AUTHOR]

The article discusses a study about the ten-year outcomes following localized prostate cancer treatment using high-dose, intensity-modulated radiation therapy (IMRT). The study involves 170 prostate cancer patients, 91 of whom have been given three months of neoadjuvant androgen deprivation therapy (N-ADT) prior to radiation treatment. Results of the study indicate that patients receiving IMRT have relatively low failure rates in the ten years that follow the treatment. Findings show how high-dose IMRT is tolerated among such patients.

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Background: The standard treatment modalities for prostate cancer include surgery, chemotherapy, hormonal therapy and radiation therapy or any combination depending on the stage of the tumour. Radiation therapy is a common and effective treatment modality for low-intermediate-risk patients with localised prostate cancer, to treat the intact prostate and seminal vesicles or prostate bed post prostatectomy. However, for high-risk patients with lymph node involvement, treatment with radiation will usually include treatment of the whole pelvis to cover the prostate and seminal vesicles or prostate bed and the pelvic lymph nodes followed by a boost delivery dose to the prostate and seminal vesicles or prostate bed. Materials and Methods: We retrospectively analysed the treatment plans for 179 prostate cancer patients treated at the cancer centre with the volumetric-modulated arc therapy (VMAT) technique via RapidArc using 6 MV photon beam. Patients were either treated with a total prescription dose of 78 Gy in 39 fractions for patients with intact prostate or 66 Gy in 33 fractions for post prostatectomy patients. Results: There were 114 (64%) patients treated with 78 Gy/39 and 65 (36%) treated with 66 Gy/34. The mean homogeneity index (HI), conformity index (CI) and uniformity index (UI) for the PTV-primary of patients treated with 78 Gy are 0.06 ± 0.01, 1.04 ± 0.01 and 0.99 ± 0.01, respectively, and the corresponding mean values for patients treated with 66 Gy are 0.06 ± 0.02, 1.05 ± 0.01 and 0.99 ± 0.01, respectively. The mean PTV-primary V95%, V100% and V105% are 99.5 ± 0.5%, 78.8 ± 12.2% and 0.1 ± 0.5%, respectively, for patients treated with 78 Gy and 99.3 ± 0.9%, 78.1 ± 10.6% and 0.1 ± 0.4%, respectively, for patients treated with 66 Gy. The rectal V50Gy, V65Gy, V66.6Gy, V70Gy, V75Gy and V80Gy are 26.8 ± 9.1%, 14.2 ± 5.3%, 13.1 ± 5.0%, 10.8 ± 4.3%, 6.9 ± 3.1% and 0.1 ± 0.1%, respectively, for patients treated with 78 Gy and 33.7 ± 8.4%, 14.1 ± 4.5%, 6.7 ± 4.5%, 0.0 ± 0.2%, 0.0% and 0.0%, respectively, for patients treated with 66 Gy. Conclusion: The use of VMAT technique for radiation therapy of high-risk prostate cancer patients is an efficient and reliable method for achieving superior dose conformity, uniformity and homogeneity to the PTV and minimal doses to the organs at risk. Results from this study provide the basis for the development and implementation of consistent treatment criteria in radiotherapy programs, have the potential to establish an evaluation process to define a consistent, standardised and transparent treatment path for all patients that reduces significant variations in the acceptability of treatment plans and potentially improve patient standard of care. [ABSTRACT FROM AUTHOR]

Objective: To describe the natural history, reconstructive solutions, and functional outcomes of those men undergoing pubectomy and urinary reconstruction after prostate cancer treatment. Patients and Methods: This study retrospectively identified 25 patients with a diagnosis of urosymphyseal fistula (UF) following prostate cancer therapy who were treated with urinary reconstruction with pubectomy. This study describes the natural history, reconstructive solutions, and functional outcomes of this cohort. Results: All 25 patients had a history of pelvic radiotherapy for prostate cancer. The median (interquartile range [IQR]) time from prostate cancer treatment to diagnosis of UF was 11 (6, 16.5) years. The vast majority of men (24/25; 96%) presented with debilitating groin pain during ambulation. Posterior urethral stenosis was common (20/25; 80%), with 60% having repetitive endoscopic treatments. Culture of pubic bone specimens demonstrated active infection in 80%. Discordance between preoperative urine and intraoperative bone cultures was common, 21/22 (95.5%). After surgery, major 90‐day complications (Clavien–Dindo Grade III and IV) occurred in eight (32%) patients. Pain was significantly improved, with resolution of pain (24/25; 96%) and restoration of function, the median (IQR) preoperative Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 3 (2, 3) vs median postoperative ECOG PS score of 0 (0, 1). Conclusion: Endoscopic urethral manipulation after radiation for prostate cancer is a risk factor for UF. Conservative management will not provide symptom resolution. Fistula decompression, bone resection, and urinary reconstruction effectively treats chronic infection, improves pain and ECOG PS scores. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze the outcomes of patients with recurrent prostate cancer (PCa) who received salvage cryotherapy (SC) in our institution. Biochemical recurrence (BCR) after definitive radiotherapy or brachytherapy for PCa is usually managed with long-term androgendeprivation therapy (ADT). In selected cases, salvage therapies might delay ADT and its side effects. Materials and Methods: All patients who received SC from 2014 to 2018 in our institution were evaluated retrospectively. Results: A total of 17 patients were included, with a median age at SC of 72.0 (range 60-77) years. The median prostate-specific antigen (PSA) before SC was 4.25 [interquartile range (IQR) 3.1-7.6] ng/mL. The median time to BCR was 18.8 (IQR 13.5-32.1) months after SC. The median PSA nadir after SC was 0.49 (IQR 0.09-1.0) ng/mL. With a median follow-up of 43 (range, 11-78) months, 7 (41%) patients had a recurrence. Of those patients, two received ADT, while others were managed conservatively. The biochemical progression-free survival (bPFS) time of patients with PSA nadir <0.5 ng/mL was 56.0 vs. 22.5 months (log-rank test, p=0.012). Gleason score =8 at diagnosis and PSA before SC >8 ng/mL were also associated with shorter bPFS (log-rank test, p<0.05). De novo urinary incontinence was reported in 5 (29.4%) patients. The 3- and 5-year PCa-specific survival rates were 93.3% and 85.6%, respectively. Conclusion: SC might be considered with acceptable oncological and functional results. Until randomized controlled trials are performed and available, series such as ours may help widen our views on all therapeutic possibilities after primary treatment failure in PCa. [ABSTRACT FROM AUTHOR]

Aim: The aim of this work was to determine the knowledge gap in the field of erectile function (EF) after colorectal cancer surgery and investigate and compare long‐term male EF in colon and rectal cancer survivors in a national population. Method: Danish male patients alive without evidence of recurrence who were treated for colon or rectal cancer between May 2001 and December 2014 were invited to participate. Using the International Index of Erectile Function (IIEF) score the derived dichotomized erectile dysfunction (ED) was defined as moderate/severe or no/mild. Patients were grouped based on type of surgery [colon resection, rectal resection (RR) or local resection] and stratified for stoma, preoperative radiotherapy (RT), age and American Society of Anesthesiologists (ASA) score. Results: Of 10 037 eligible patients, 4334 responded (43.18%). The EF score was significantly lower for RR (mean 12.14) compared with both colon resection (mean 15.82) and local resection (mean 14.81) (p < 0.0001). No significant difference between colon resection and local resection was found (p = 0.29). Both a stoma and the use of RT were independent risk factors for ED. After excluding patients with stoma and RT and adjusting for age and ASA score, RR still had a higher risk of ED (OR 1.42, CI 1.20–1.67) compared with colon resection. Conclusion: RR has a negative affect on EF. No difference between patients who underwent colon resection and local resection was found. RT and stoma were independent risk factors for ED. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) is one of the major but underreported concerns in cancer patients and survivors. It can lead to depression, lack of intimacy between the couple, and impaired quality of life. The causes of erectile dysfunction are psychological distress and endocrinal dysfunction caused by cancer itself or side effect of anticancer treatment like surgery, radiotherapy, chemotherapy and hormonal therapy. The degree of ED depends on age, pre-cancer or pre-treatment potency level, comorbidities, type of cancer and its treatment. Treatment options available for ED are various pharmacotherapies, mechanical devices, penile implants, or reconstructive surgeries. A complete evaluation of sexual functioning should be done before starting anticancer therapy. Management should be individualized and couple counseling should be an integral part of the anticancer treatment. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the effect of a hydrogel spacer on intrafractional prostate motion during CyberKnife treatment. The retrospective study enrolled 24 patients (with the hydrogel spacer = 12, without the hydrogel spacer = 12) with two fiducial markers. Regarding intrafractional prostate motion, the offset values (mm) of three axes (X‐axis; superior [+] to inferior [−], Y‐axis; right [+] to left [−], Z‐axis; posterior [+] to anterior [−]) obtained from fiducial markers position between a digitally reconstructed radiographs images and live images in the Target Locating System were used, and extracted from generated log files. The mean values of the offset and each standard deviation were calculated for each patient, and both the groups were compared. For all the patients, a total of 2204 offset values and timestamps (without the hydrogel spacer group: 1065, with the hydrogel spacer group: 1139) were recorded for the X‐, Y‐, and Z‐axes, respectively. The offset values (mean ± standard deviation) for the X‐, Y‐, and Z‐axes were −0.04 ± 0.92 mm, −0.03 ± 0.97 mm (P = 0.66), 0.02 ± 0.51, −0.02 ± 0.49 mm (P = 0.50), and 0.56 ± 0.97 mm, 0.34 ± 1.07 mm (P = 0.14), in patients inserted without or with the hydrogel spacer, respectively. There was no effect of a hydrogel spacer on the intrafractional prostate motion in the three axes during CyberKnife treatment for prostate cancer. [ABSTRACT FROM AUTHOR]

Ionizing radiation (IR) is an important cancer treatment approach. However, radioresistance eventually occurs, resulting in poor outcomes in patients with cancer. Radioresistance is associated with multiple signaling pathways, particularly pro-survival signaling pathways. The extracellular signal-regulated kinase 1/2 (ERK1/2) cascade is an important signaling pathway that initiates several cellular processes and is regulated by various stimuli, including IR. Although numerous studies have demonstrated the pro-survival effects of active ERK, activation of ERK has also been associated with cell death, indicating that radiosensitization may occur by ERK stimulation. In this context, the present review describes the associations between ERK signaling, cancer and IR, and discusses the association between ERK and its pro-survival function in cancer cells, including stimuli, molecular mechanisms, clinical use of inhibitors and underlying limitations. Additionally, the present review introduces the view that active ERK may induce cell death, and describes the potential factors associated with this process. This review describes the various outcomes induced by active ERK to prompt future studies to aim to enhance radiosensitivity in the treatment of cancer. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the current prostate cancer screening and treatment paradigm in light of recently published long‐term results of major screening and treatment trials. Methods: Historical review of the evolution of the diagnosis and treatment of prostate cancer followed by a detailed summary of the findings and differences among the three major screening trials and the three major treatment trials. Results: Prostate‐specific antigen (PSA) testing can identify clinically significant prostate cancer and has produced a significant stage shift and is the likely explanation for the decline in prostate cancer mortality. Unfortunately, PSA testing predominantly identifies low‐grade disease that is unlikely to progress during a patient's lifetime leading to substantial diagnosis of indolent disease. Treatment with radical prostatectomy (RP) appears to benefit primarily younger men (aged <65 years) with intermediate‐grade disease. Too few men with low‐grade disease benefit from RP to justify intervening in all. Unfortunately, high‐grade prostate cancer often progresses despite surgery and radiation. Conclusion: The primary PSA testing paradigm is wrong. Rather than attempting to identify all prostate cancers as early as possible, testing objectives should shift towards identifying men likely to harbour clinically significant disease. These are the men who appear to benefit from early diagnosis and intervention, including the earlier use of antiandrogen therapy prior to widespread metastases. [ABSTRACT FROM AUTHOR]

Purpose: Although the clinical significance of a diagnosis of prostate cancer for some men is debated, for many men it leads to significant morbidity and mortality. Radical treatment of clinically localized prostate cancer has been shown to improve survival in men with intermediate or high-risk disease. There is no high level evidence to support the superiority of radical prostatectomy, with or without adjuvant or salvage external beam radiotherapy in comparison to definitive radiotherapy with or without androgen deprivation, and the choice should be individualized. External beam radiation therapy practices are in constant evolution, and numerous strategies have been investigated to improve either efficacy or reduce toxicity, or both. Methods: Randomized controlled trials investigating strategies to improve efficacy, reduce toxicity, or both of external beam radiotherapy have been reviewed in men with prostate cancer without nodal or distant metastases. These strategies include the use of neo-adjuvant and adjuvant androgen deprivation, dose-escalation, hypofractionation, whole pelvic radiation therapy, incorporation of improved imaging, image- guided radiation therapy, and adjuvant systemic therapy. The evidence to date for these strategies is discussed, noting limitations in applying the results of reported trials to men treated in contemporary settings. Results: A number of strategies have shown improvements in biochemical control using external beam radiotherapy. To date, only with the use of androgen deprivation therapy has this translated into improvements in disease specific and overall survival. This may reflect the long natural history of prostate cancer and high incidence of competing risks. Technological advances have enabled dose escalation with reduced toxicity, of paramount importance given the long natural history. Results: The use of external beam radiation therapy in prostate cancer is evolving with numerous strategies incorporated to improve outcomes. The optimum dose and fractionation and use of androgen deprivation or systemic adjuvants for each man is unclear based on current evidence and prognostic and predictive parameters. Patient preferences play an important role in chosen therapy. It is hoped that future studies better capture all prostate cancer- and treatment- related morbidity to clarify the optimal therapy choices for each man with prostate cancer. [ABSTRACT FROM AUTHOR]

Background: It has been hypothesized that radiotherapy (RT) techniques delivering radiations to larger volumes (IMRT, VMAT) are potentially associated with a higher risk of second primary tumors. The aim of this study was to analyse the impact of RT technique (3D-CRT vs IMRT/VMAT) on the incidence of second tumors in prostate cancer (PCa) patients.Methods: A retrospective study on 2526 previously irradiated PCa patients was performed. Patients were treated with 3D-CRT (21.3%), IMRT (68.1%), or VMAT (10.6%). Second tumors incidence was analysed in 3 categories: pelvic, pelvic and abdominal, and "any site". The correlation with RT technique was analysed using log-rank test and Cox's proportional hazard method.Results: With a median follow-up of 72 months (range: 9-185), 92 (3.6%) cases of second tumors were recorded with 48 months (range: 9-152) median interval from RT. Actuarial 10-year second tumor free survival (STFS) was 87.3%. Ten-year STFS in patients treated with 3D-CRT and IMRT/VMAT was 85.8 and 84.5%, respectively (p: .627). A significantly higher 10-year cumulative incidence of second tumors in the pelvis was registered in patients treated with IMRT/VMAT compared to 3D-CRT (10.7% vs 6.0%; p: .033). The lower incidence of second pelvic cancers in patients treated with 3D-CRT was confirmed at multivariable analysis (HR: 2.42, 95%CI: 1.07-5.47, p: .034).Conclusions: The incidence of second pelvic tumors after RT of PCa showed a significant correlation with treatment technique. Further analyses in larger series with prolonged follow-up are needed to confirm these results. [ABSTRACT FROM AUTHOR]

The article presents a study on diagnosis of genitourinary cancer and methodology used for its treatment in Australia. Various topics discussed include use of steroid in its treatment, cystoprostatectomy, complications in treatment morbidity, systems of disease progression and clinical trials on beam mortality.

This study aims to report the incidence of adverse cochlear effects when treating patients of HNSCC with different radiation techniques and to compare the effect of different treatment modalities on the cochlea. This prospective observational study took place in a tertiary care centre, of 132 individual ears from 66 patients of HNSCC treated with conventional RT (group-1), IMRT (group-2), conventional RT with chemotherapy (group-3) and IMRT in combination with chemotherapy (group-4). Pure tone audiometry was performed during the follow-up period at 3 months and 1 year of completion of therapy. Correlation of audiometric change of both the ears at high frequencies (pure tone average 4 kHz, 6 kHz, 8 kHz), low frequencies (pure tone average 0.5–2 kHz) and BC (average 500–4 kHz) with series of factors were analyzed. There was a significant deterioration of hearing threshold 1 year after complete treatment, in all groups. There was an average drop in BC (0–1 year) by 19.63 ± 31.25% in group-2, 24.57 ± 21.96% in group-1 and a drop of 36.48 ± 43.97% and 70.78 ± 21.11% in group-3 and group-4 respectively. When we compared the audiometric change (PTAv at high and low frequency) from 0 to 1 year of group-1&2 the p value was significant (p = 0.050 at high frequency, p = 0.040 at low frequency). The audiological outcome of the different treatment modalities when compared, it was observed that the maximum hearing loss was in group-4 (IMRT with Chemotherapy) followed by group-3 (RTCT), group-1 (Conventional RT) and group-2 (IMRT). [ABSTRACT FROM AUTHOR]

Although prostate cancer control using radiotherapy is dose‐dependent, dose–volume effects on late toxicities in organs at risk, such as the rectum and bladder, have been observed. Both protons and carbon ions offer advantageous physical properties for radiotherapy, and create favorable dose distributions using fewer portals compared with photon‐based radiotherapy. Thus, particle beam therapy using protons and carbon ions theoretically seems suitable for dose escalation and reduced risk of toxicity. However, it is difficult to evaluate the superiority of particle beam radiotherapy over photon beam radiotherapy for prostate cancer, as no clinical trials have directly compared the outcomes between the two types of therapy due to the limited number of facilities using particle beam therapy. The Japanese Society for Radiation Oncology organized a joint effort among research groups to establish standardized treatment policies and indications for particle beam therapy according to disease, and multicenter prospective studies have been planned for several common cancers. Clinical trials of proton beam therapy for intermediate‐risk prostate cancer and carbon‐ion therapy for high‐risk prostate cancer have already begun. As particle beam therapy for prostate cancer is covered by the Japanese national health insurance system as of April 2018, and the number of facilities practicing particle beam therapy has increased recently, the number of prostate cancer patients treated with particle beam therapy in Japan is expected to increase drastically. Here, we review the results from studies of particle beam therapy for prostate cancer and discuss future developments in this field. [ABSTRACT FROM AUTHOR]

External beam radiotherapy has changed dramatically over several decades with the improvement of computer hardware and software, and machinery developments. Intensity‐modulated radiation therapy is the most sophisticated technique for all cancer treatment with radiation therapy, and is widely disseminated and available for daily use in many countries. Several retrospective and prospective studies have shown that intensity‐modulated radiation therapy reduces the radiation dose in the organs at risk with diminished rates of acute and late toxicity, even with higher doses (>74 Gy). An important technique for the clinical use of intensity‐modulated radiation therapy is image‐guided radiation therapy. The clinical benefit for prostate image‐guided radiation therapy has been assessed by comparing the outcomes of patients with either the image‐guided radiation therapy or non‐image‐guided radiation therapy technique. These studies have shown that image‐guided radiation therapy significantly decreases acute and late rectal and bladder toxicities. Randomized trials and meta‐analysis have shown that higher doses result in better biochemical control. More recently, hypofractionated radiation therapy comparing hypofractionated radiation therapy versus conventional fractionated radiation therapy have shown that hypofractionated radiation therapy produces biochemical control and toxicity rated similar to those produced by conventional fractionated radiation therapy. The clinical use of ultrahypofractionated radiation therapy and simultaneous integrated boost technique is necessary to evaluate its further safety and benefits. Intensity‐modulated radiation therapy is also widely accepted in the field of salvage therapy and for the patients with distant oligometastases. The purpose of the present review is to summarize the history of intensity‐modulated radiation therapy, new techniques for intensity‐modulated radiation therapy, hypofractionation and future directions for prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Smoking cessation is a key step towards improving cancer care and outcomes. However, smoking cessation interventions are underprovided in oncology settings. Within Jordan's only comprehensive oncology center, we sought to evaluate receipt of care at a smoking cessation clinic and the effect of assisted abstinence through the smoking cessation clinic on short-term (two-year) survival after a cancer diagnosis.Methods: We employed a retrospective cohort study design. Cancer registry and smoking cessation clinic data for adult Jordanian cancer patients diagnosed between 2009 and 2016, who also were cigarette smokers, and who received full treatment at King Hussein Cancer Center, were analyzed. Specifically, descriptive statistics of patients who visited the smoking cessation clinic were generated, and short-term (two-year) hazard of death of patients based on whether or not smoking cessation clinic-assisted abstinence occurred, were evaluated.Results: There were 3403 patients who met our inclusion criteria. Approximately 21% of cancer patients were seen at the smoking cessation clinic, and significant demographic and clinical disparities in who was being seen [at the smoking cessation clinic] existed. In 2387 patients with available survival data, smokers who never went to the smoking cessation clinic (or were seen only once, or seen a year or more from diagnosis) had a hazard of death 2.8 times higher than smokers who had visited the smoking cessation clinic and who also confirmed they had not smoked on atleast two of their 3-, 6- or 12-month follow-up visits (95% confidence interval [CI] = 1.7-4.6). Non-abstainers at the smoking cessation clinic exhibited a similar disadvantage (HR 2.7, 95% CI 1.4-5.0).Conclusions: Although evidence-based smoking cessation interventions increase the likelihood of abstinence and can lower the short-term hazard of death during cancer treatment, there is a deprioritization of smoking cessation interventions during cancer care, as indicated by low proportions of patients seen at the smoking cessation clinic. Our findings emphasize the importance of promoting interventions to avail smoking cessation interventions in oncology settings within the cancer treatment phase. [ABSTRACT FROM AUTHOR]

Highlights from the article: The treatment of prostate cancer represents a significant fraction of all radiotherapy treatments, however, the tangible benefits of the use of proton therapy for prostate cancer are still hotly debated. In the case of prostate cancer, proton therapy usually deploys a simple plan consisting of two lateral beams and achieves the desired target coverage and OAR sparing as well as the conformity comparable to the much more complicated photon external beam plans.[[4]] From the physics perspective, the marked reduction in integral dose and simplicity of treatment plan make proton therapy the logical choice for prostate cancer. Radical prostatectomy, external beam radiotherapy or external beam radiotherapy with brachytherapy boost and disease progression and mortality in patients with Gleason score 9-10 prostate cancer.

Purpose: The aim of this study was to identify volume changes and dose variations of rectum and bladder during radiation therapy in prostate cancer (PC) patients. Materials and Methods: We analyzed 20 patients with PC treated with helical tomotherapy. Daily image guidance was performed. We re-contoured the entire bladder and rectum including its contents as well as the organ walls on megavoltage computed tomography once a week. Dose variations were analyzed by means of Dmedian, Dmean, Dmax, V10 to V75, as well as the organs at risk (OAR) volume. Further, we investigated the correlation between volume changes and changes in Dmean of OAR. Results: During treatment, the rectal volume ranged from 62% to 223% of its initial volume, the bladder volume from 22% to 375%. The average Dmean ranged from 87% to 118% for the rectum and 58% to 160% for the bladder. The Pearson correlation coefficients between volume changes and corresponding changes in Dmean were -0.82 for the bladder and 0.52 for the rectum. The comparison of the dose wall histogram (DWH) and the dose volume histogram (DVH) showed that the DVH underestimates the percentage of the rectal and bladder volume exposed to the high dose region. Conclusion: Relevant variations in the volume of OAR and corresponding dose variations can be observed. For the bladder, an increase in the volume generally leads to lower doses; for the rectum, the correlation is weaker. Having demonstrated remarkable differences in the dose distribution of the DWH and the DVH, the use of DWHs should be considered. [ABSTRACT FROM AUTHOR]

Objective: To identify trends of patients’ urinary and sexual dysfunctions from a clinical and psychological perspective and understand whether sociodemographic and medical predictors could differentiate among patients following different one-year longitudinal trajectories. Methods: An Italian sample of 478 prostate cancer patients undergone Robot-Assisted Radical Prostatectomy completed the EPIC-26 survey between July 2015 and July 2016 at the pre-hospitalization (T0), 45 days (T1) and 3 (T2), 6 (T3), 9 (T4), and 12 months (T5) after surgery. Sociodemographic and clinical characteristics (age, BMI, diabetes, nerve-sparing procedure) were also collected. Latent Class Growth Analysis was conducted separately for sexual dysfunction and urinary incontinence EPIC-26 subscales. The association between membership in the two longitudinal trajectories of urinary and sexual dysfunctions was assessed by considering Chi-square test and its related contingency table. Results: People who have a high level of urinary incontinence at T1 are likely to have a worse recovery. Age, BMI and pre-surgical continence may affect the level of incontinence at T1 and the recovery trajectories. Patients with low and moderate sexual problems at T1 can face a moderate linear recovery, while people with high level of impotence immediately after surgery may take a longer period to solve sexual dysfunctions. Age and the pre-surgical sexual condition may impact the recovery. Finally, a great proportion of patients reported both steady problems in sexual function and constant high levels of urinary incontinence over time. Conclusions: This study highlights different categories of patients at risk who may be important to know in order to develop personalized medical pathways and predictive models in a value-based healthcare. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this article is to review the most commonly used tumor markers in abdominal and pelvic tumors, describe their limitations and explain how to use them in the context of known cancer in order to optimize multidisciplinary care of oncologic patients. Conclusion: Tumor markers are important for the diagnosis, staging, monitoring of treatment and detection of recurrence in many cancers. This knowledge is crucial in the daily interpretation of images of oncologic and non-oncologic patients. However, radiologists should also be aware of the limitations of the most commonly used tumor markers and they should not be used solely, but interpreted in conjunction with diagnostic imaging, clinical history and physical examination that will help optimize the multidisciplinary care and management of oncologic patients. [ABSTRACT FROM AUTHOR]

Background: Prognostic stratification is the cornerstone of management in nonmetastatic prostate cancer (PCa). However, existing prognostic models are inadequate-often using treatment outcomes rather than survival, stratifying by broad heterogeneous groups and using heavily treated cohorts. To address this unmet need, we developed an individualised prognostic model that contextualises PCa-specific mortality (PCSM) against other cause mortality, and estimates the impact of treatment on survival.Methods and Findings: Using records from the United Kingdom National Cancer Registration and Analysis Service (NCRAS), data were collated for 10,089 men diagnosed with nonmetastatic PCa between 2000 and 2010 in Eastern England. Median follow-up was 9.8 years with 3,829 deaths (1,202 PCa specific). Totals of 19.8%, 14.1%, 34.6%, and 31.5% of men underwent conservative management, prostatectomy, radiotherapy (RT), and androgen deprivation monotherapy, respectively. A total of 2,546 men diagnosed in Singapore over a similar time period represented an external validation cohort. Data were randomly split 70:30 into model development and validation cohorts. Fifteen-year PCSM and non-PCa mortality (NPCM) were explored using separate multivariable Cox models within a competing risks framework. Fractional polynomials (FPs) were utilised to fit continuous variables and baseline hazards. Model accuracy was assessed by discrimination and calibration using the Harrell C-index and chi-squared goodness of fit, respectively, within both validation cohorts. A multivariable model estimating individualised 10- and 15-year survival outcomes was constructed combining age, prostate-specific antigen (PSA), histological grade, biopsy core involvement, stage, and primary treatment, which were each independent prognostic factors for PCSM, and age and comorbidity, which were prognostic for NPCM. The model demonstrated good discrimination, with a C-index of 0.84 (95% CI: 0.82-0.86) and 0.84 (95% CI: 0.80-0.87) for 15-year PCSM in the UK and Singapore validation cohorts, respectively, comparing favourably to international risk-stratification criteria. Discrimination was maintained for overall mortality, with C-index 0.77 (95% CI: 0.75-0.78) and 0.76 (95% CI: 0.73-0.78). The model was well calibrated with no significant difference between predicted and observed PCa-specific (p = 0.19) or overall deaths (p = 0.43) in the UK cohort. Key study limitations were a relatively small external validation cohort, an inability to account for delayed changes to treatment beyond 12 months, and an absence of tumour-stage subclassifications.Conclusions: 'PREDICT Prostate' is an individualised multivariable PCa prognostic model built from baseline diagnostic information and the first to our knowledge that models potential treatment benefits on overall survival. Prognostic power is high despite using only routinely collected clinicopathological information. [ABSTRACT FROM AUTHOR]

Background: Recently, the clinical outcome of prostate cancer treated by hypofractionated radiation therapy has been reported. However, there are few reports from Japan. In Hidaka Hospital, hypofractionated intensity-modulated radiotherapy (HIMRT) for prostate cancer was initiated in 2007. The purpose of this study is to analyze the long-term outcome. Methods: Ninety-two patients with localized prostate cancer treated with HIMRT at Hidaka Hospital between 2007 and 2009 were retrospectively analyzed. HIMRT was delivered using TomoTherapy. The prescription dose was 66 Gy at 95% of the PTV in 22 fractions performed 3 days a week over 7 weeks in all patients. The overall survival rate, biochemical relapse-free rate, and acute and late toxicities were evaluated. Results: The median follow-up duration was 78 (range 14–100) months. The median age at the start of the HIMRT was 72 (range 46–84) years. The disease characteristics were as follows: stage T1c, 45; T2a, 20; T2b, 5; T2c, 1; T3a, 13; T3b, 6; T4, 2; Gleason score 6, 13; 7, 44; 8, 20; 9, 15; 10, 0; pretreatment PSA ≤10 ng/mL, 42; 10 to ≤20, 27; and >20, 23. According to the D’Amico classification system, 10, 37, and 45 patients were classified as low-risk, intermediate-risk, and high-risk. The overall survival rate, the cause-specific survival rate, and the biochemical relapse-free rate at 5 years was 94.7%, 100% and 98.9%, respectively. Severe acute toxicity (grade 3 or more) was not observed. The late urinary toxicity was 52.2% in grade 0, 28.3% in grade 1, 19.6% in grade 2, and 2.2% in grade 3. The late rectal toxicity was 78.3% in grade 0, 7.6% in grade 1, 9.8% in grade 2, and 4.3% in grade 3. Conclusions: The present study demonstrated that HIMRT using TomoTherapy for prostate cancer has a favorable outcome with tolerable toxicity. [ABSTRACT FROM AUTHOR]

Background: Prospective evaluation of the results of volumetric modulated arc therapy (VMAT) for sinonasal cancer compared to 3D conformal radiation therapy (3DCRT). Materials and Methods: We prospectively evaluated 34 patients (pts) treated with postoperative VMAT with simultaneous integrated boost (SIB; RapidArc) from 2011 to 2015. These pts were retrospectively compared with 24 pts treated with 3DCRT from 2003 to 2011. The two sets were not significantly different on sex, mean age, tumor site, stage, histology. Efficacy and toxicity were evaluated. Results: Median follow‐up was 45 months (range: 6‐143 months). Three‐year overall survival was 85.2% in VMAT‐SIB versus 65.2% in 3DCRT (P = .02). Three‐year local control was 81.2% in VMAT‐SIB versus 62.5% in 3DCRT (P = .04). There was a reduction of acute (<0.09) and late (0.03) ocular toxicity of grade ≥ 2 for pts with VMAT‐SIB. Conclusion: VMAT significantly improved local control and overall survival in sinonasal cancer with lower rate of toxicity. [ABSTRACT FROM AUTHOR]

Objectives: No study has reported clinical results of external-beam radiotherapy specifically for T3b prostate cancer. The possibility of escalating the dose to the involved seminal vesicles (ISV) while respecting the dose constraints in the organs at risk is thus so far not clearly demonstrated. The objective of the study was to analyze the dose distribution and the clinical outcome in a large series of patients who received IMRT for T3b prostate cancer. Materials and methods: This retrospective analysis included all patients who received IMRT and androgen deprivation therapy for T3b prostate cancer, between 2008 and 2017, in six French institutions, with available MRI images and dosimetric data. Results: A total of 276 T3b patients were included. The median follow-up was 26 months. The median (range) prescribed doses (Gy) to the prostate and to the ISV were 77 (70–80) and 76 (46–80), respectively. The dose constraint recommendations were exceeded in less than 12% of patients for the rectum and the bladder. The 5-year risks of biochemical and clinical recurrences and cancer-specific death were 24.8%, 21.7%, and 10.3%, respectively. The 5-year risks of local, pelvic lymph node, and metastatic recurrences were 6.4%, 11.3%, and 15%, respectively. The number of involved lymph nodes (≤ 2 or ≥ 3) on MRI was the only significant prognostic factor in clinical recurrence (HR 9.86) and death (HR 2.78). Grade ≥ 2 acute and 5-year late toxicity rates were 13.2% and 12% for digestive toxicity, and 34% and 31.5% for urinary toxicity, respectively. The dose to the pelvic lymph node and the age were predictive of late digestive toxicity. Conclusion: IMRT for T3b prostate cancer allows delivery of a curative dose in the ISV, with a moderate digestive toxicity but a higher urinary toxicity. Lymph node involvement increases the risk of recurrence and death. [ABSTRACT FROM AUTHOR]

In this work we present a methodology able to use harmonized PET/CT imaging in dose painting by number (DPBN) approach by means of a robust and accurate treatment planning system. Image processing and treatment planning were performed by using a Matlab-based platform, called CARMEN, in which a full Monte Carlo simulation is included. Linear programming formulation was developed for a voxel-by-voxel robust optimization and a specific direct aperture optimization was designed for an efficient adaptive radiotherapy implementation. DPBN approach with our methodology was tested to reduce the uncertainties associated with both, the absolute value and the relative value of the information in the functional image. For the same H&N case, a single robust treatment was planned for dose prescription maps corresponding to standardized uptake value distributions from two different image reconstruction protocols: One to fulfill EARL accreditation for harmonization of [18F]FDG PET/CT image, and the other one to use the highest available spatial resolution. Also, a robust treatment was planned to fulfill dose prescription maps corresponding to both approaches, the dose painting by contour based on volumes and our voxel-by-voxel DPBN. Adaptive planning was also carried out to check the suitability of our proposal. Different plans showed robustness to cover a range of scenarios for implementation of harmonizing strategies by using the highest available resolution. Also, robustness associated to discretization level of dose prescription according to the use of contours or numbers was achieved. All plans showed excellent quality index histogram and quality factors below 2%. Efficient solution for adaptive radiotherapy based directly on changes in functional image was obtained. We proved that by using voxel-by-voxel DPBN approach it is possible to overcome typical drawbacks linked to PET/CT images, providing to the clinical specialist confidence enough for routinely implementation of functional imaging for personalized radiotherapy. [ABSTRACT FROM AUTHOR]

The traditional open retropubic radical prostatectomy has an established role in the treatment of prostate cancer. However, it is well known to be morbid procedure with high complication rate. This bad reputation prevented utilizing it on a large scale for high risk prostate cancer. Utilizing the da Vinci® to preform radical prostatectomy decreased the morbidity of the procedure. Since the introduction of robotic prostatectomy, there have been hot debates on its role in the treatment of high risk disease. In this article we reviewed the current evidence on utilizing the surgical system in treating high risk organ confined prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Peritumoral inflammation—a response mainly involving polimorphonuclear neutrophils—has traditionally been thought protumoral in its effects. In recent years, however, a number of studies have indicated that it may play an important antitumoral role. This discrepancy has been difficult to explain. Methods and findings: This work describes a tool for simulating tumor growth that obeys the universal model of tumor growth dynamics, and shows through its use that low intensity peritumoral inflammation exerts a protumoral effect, while high intensity inflammation exerts a potent antitumoral effect. Indeed, the simulation results obtained indicate that a sufficiently strong antitumoral effect can reverse tumor growth, as has been suggested several times in the clinical literature. Conclusions: The present result indicate that an ‘immunological threshold’ must exist, marking the boundary between states in which peritumoral inflammation is either harmful or beneficial. These findings lend support to the idea that stimulating intense peritumoral inflammation could be used as a treatment against solid tumors. [ABSTRACT FROM AUTHOR]

Background: Soft tissue sarcomas are a heterogeneous and rare group of solid tumors of mesenchymal origin that can arise anywhere in the body. Although surgical resection is the mainstay of treatment for patients with localized disease, disease recurrence is common and 5-year overall survival is poor (~ 65%). Both radiation therapy and conventional chemotherapy are used to reduce local and distant recurrence. However, the utility of radiation therapy is often limited by disease location (in the case of retroperitoneal sarcomas, for instance) while systemic therapy with conventional lines of chemotherapy offer limited efficacy and are often poorly tolerated and associated with significant toxicity. Within the past decade, major advances have been made in the treatment of other malignancies including melanoma, renal cell carcinoma, and non-small cell lung carcinoma with the advent of immune-checkpoint inhibitors such as ipilimumab (anti-CTLA4), pembrolizumab (anti-PD1), and nivolumab (anti-PD1). The recently published SARC028 (NCT02301039), an open label, phase II, multicenter trial of pembrolizumab in patients with advanced bone and soft tissue sarcomas reported promising activity in select histologic subtypes of advanced STS, including undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.Methods: There is a clear need for novel and effective adjuncts in the treatment of STS. We hypothesize that immune checkpoint blockade will be effective in patients with surgically resectable primary or locally recurrent dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma when administered in the neoadjuvant setting. The primary aim of this phase II, single-center, open label, randomized non-comparative trial is to determine the pathologic response to neoadjuvant nivolumab monotherapy and combination nivolumab/ipilimumab in patients with resectable dedifferentiated liposarcoma of the retroperitoneum or undifferentiated pleomorphic sarcoma of the trunk or extremity treated with concurrent standard of care neoadjuvant radiation therapy.Discussion: This study will help define the role of single agent anti-PD1 and combination anti-CTLA4 and anti-PD1 therapy in patients with surgically resectable dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma.Trial Registration: ClinicalTrials.gov NCT03307616 , registered October 12, 2017. [ABSTRACT FROM AUTHOR]

Background: Differentiated thyroid cancer typically has an indolent clinical course but can cause significant morbidity by local progression. Oncologic surgical resection can be technically difficult due to the proximity to critical normal structures in the neck. Our objective was to review the safety, feasibility, and outcomes of definitive-intent intensity-modulated radiation therapy (IMRT) and to analyze whether patients receiving concurrent chemotherapy (CC-IMRT) had higher rates of disease control and survival over IMRT alone in patients with unresectable or gross residual disease (GRD). Methods: Eighty-eight patients with GRD or unresectable nonanaplastic, nonmedullary thyroid cancer treated with definitive-intent IMRT between 2000 and 2015 were identified. Local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and overall survival (OS) were evaluated using the Kaplan–Meier method. Univariate and multivariate analyses using cox regression were used to determine the impact of clinical conditions and treatment on LPFS, DMFS, and OS. Results: Of the 88 patients identified, 45 (51.1%) were treated CC-IMRT and 43 (48.9%) were treated with IMRT alone. All patients treated with CC-IMRT received weekly doxorubicin (10 mg/m2). The median follow-up among surviving patients was 40.3 months and 29.2 months for all patients. The LPFS at 4 years was 77.3%. Patients receiving CC-IMRT had higher LPFS compared with IMRT alone (CC-IMRT 85.8% vs. IMRT 68.8%, p = 0.036). The 4-year OS was 56.3% for all patients. Patients treated with CC-IMRT had higher OS compared to patients treated with IMRT alone (CC-IMRT 68.0% vs. IMRT 47.0%, p = 0.043). On multivariate analysis, receipt of concurrent chemotherapy was associated with a lower risk of death (HR 0.395, p = 0.019) and lower risk of local failure (HR 0.306, p = 0.042). Grade 3+ acute toxicities occurred in 23.9% of patients, the most frequent being dermatitis (18.2%) and mucositis (9.1%). 17.1% of patients required a percutaneous endoscopic gastrostomy (PEG) tube during or shortly after completion of RT, with 10.1% of patients needing a PEG more than 12 months after therapy. The rates of acute and late toxicities were not statistically higher in the CC-IMRT cohort, although trends towards higher toxicity in the CC-IMRT were present for dermatitis and PEG requirement. Conclusions: IMRT is a safe and effective means to achieve local control in patients with unresectable or incompletely resected nonanaplastic, nonmedullary thyroid cancer. Concurrent doxorubicin was not associated with worse toxicity and should be considered in these patients given its potential to improve local control and overall survival. [ABSTRACT FROM AUTHOR]

Purpose: To explore the utility of diffusion and perfusion changes in primary renal cell carcinoma (RCC) after stereotactic ablative body radiotherapy (SABR) as an early biomarker of treatment response, using diffusion weighted (DWI) and dynamic contrast enhanced (DCE) MRI. Methods: Patients enrolled in a prospective pilot clinical trial received SABR for primary RCC, and had DWI and DCE MRI scheduled at baseline, 14 days and 70 days after SABR. Tumours <5cm diameter received a single fraction of 26 Gy and larger tumours received three fractions of 14 Gy. Apparent diffusion coefficient (ADC) maps were computed from DWI data and parametric and pharmacokinetic maps were fitted to the DCE data. Tumour volumes were contoured and statistics extracted. Spearman’s rank correlation coefficients were computed between MRI parameter changes versus the percentage tumour volume change from CT at 6, 12 and 24 months and the last follow-up relative to baseline CT. Results: Twelve patients were eligible for DWI analysis, and a subset of ten patients for DCE MRI analysis. DCE MRI from the second follow-up MRI scan showed correlations between the change in percentage voxels with washout contrast enhancement behaviour and the change in tumour volume (ρ = 0.84, p = 0.004 at 12 month CT, ρ = 0.81, p = 0.02 at 24 month CT, and ρ = 0.89, p = 0.001 at last follow-up CT). The change in mean initial rate of enhancement and mean Ktrans at the second follow-up MRI scan were positively correlated with percent tumour volume change at the 12 month CT onwards (ρ = 0.65, p = 0.05 and ρ = 0.66, p = 0.04 at 12 month CT respectively). Changes in ADC kurtosis from histogram analysis at the first follow-up MRI scan also showed positive correlations with the percentage tumour volume change (ρ = 0.66, p = 0.02 at 12 month CT, ρ = 0.69, p = 0.02 at last follow-up CT), but these results are possibly confounded by inflammation. Conclusion: DWI and DCE MRI parameters show potential as early response biomarkers after SABR for primary RCC. Further prospective validation using larger patient cohorts is warranted. [ABSTRACT FROM AUTHOR]

Background and purpose: Incontinence, hematuria, voiding frequency and pain during voiding are possible side effects of radiotherapy among patients treated for prostate cancer. The objective of this study was to develop multivariable NTCP models for these side effects. Material and methods: This prospective cohort study was composed of 243 patients with localized or locally advanced prostate cancer (stage T1-3). Genito-urinary (GU) toxicity was assessed using a standardized follow-up program. The GU toxicity endpoints were scored using the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE 3.0) scoring system. The full bladder and different anatomical subregions within the bladder were delineated. A least absolute shrinkage and selection operator (LASSO) logistic regression analysis was used to analyze dose volume effects on the four individual endpoints. Results: In the univariable analysis, urinary incontinence was significantly associated with dose distributions in the trigone (V55-V75, mean). Hematuria was significantly associated with the bladder wall dose (V40-V75, mean), bladder dose (V70-V75), cardiovascular disease and anticoagulants use. Pain during urinating was associated with the dose to the trigone (V50-V75, mean) and with trans transurethral resection of the prostate (TURP). In the final multivariable model urinary incontinence was associated with the mean dose of the trigone. Hematuria was associated with bladder wall dose (V75) and cardiovascular disease, while pain during urinating was associated with trigone dose (V75) and TURP. No significant associations were found for increase in voiding frequency. Conclusions: Radiation-induced urinary side effects are associated with dose distributions to different organs as risk. Given the dose effect relationships found, decreasing the dose to the trigone and bladder wall may reduce the incidence of incontinence, pain during voiding and hematuria, respectively. [ABSTRACT FROM AUTHOR]

Purpose: Prostate cancer (PC) is a devastating and heterogeneous condition with diverse treatment options. When selecting treatments for patients with very high-risk PC, clinicians must consider patient comorbidities. We investigated the efficacy of the age-adjusted Charlson Comorbidity Index (ACCI) as a prognostic factor for patient outcomes after radical prostatectomy (RP). Materials and methods: We retrospectively investigated the medical records of PC patients at our institution who underwent RP from 1992 to 2010. Very high-risk PC was defined according to National Comprehensive Cancer Network guidelines. Patients with incomplete medical records or who had received neoadjuvant therapy were excluded. Preoperative comorbidity was evaluated by the ACCI, and the prognostic efficacy of the ACCI was analyzed using univariable and multivariable Cox regression, competing risk regression model and Kaplan-Meier curves. Results: Our final analysis included 228 men with a median age of 66 years (interquartile range 62–71) and median prostate specific antigen of 10.7 ng/mL. There were 41 (18%) patients with an ACCI score >3 and 88 (38.6%) patients with a biopsy Gleason score >8. Preoperative evaluation revealed that 159 patients (69.7%) had a non-organ confined tumor (≥T3). Following RP, 8-year prostate cancer-specific survival (PCSS) and overall survival (OS) rates were 91.6% and 83.4%, respectively. Competing risk regression analysis revealed that ACCI was significantly associated with other-cause survival and OS (p<0.05). Conclusion: The ACCI is an effective prognostic factor for other-cause survival and OS in very high-risk PC patients. RP should be considered carefully for patients with an ACCI score >3. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the efficacy of docetaxel in castration-resistant prostate cancer (CRPC) patients with intraductal carcinoma of the prostate (IDC-P).Patients and methods: We retrospectively identified 79 CRPC patients with distant metastasis at initial diagnosis from June 2002 to January 2014. All patients received initial androgen deprivation therapy and 46 received docetaxel chemotherapy after progressing to CRPC. The primary outcome of interest was cancer-specific survival (CSS) from the time of CRPC diagnosis. The Cox regression model was used to confirm whether IDC-P and docetaxel would act as independent factors for prognosis.Results: IDC-P was found in 62 of 79 patients. The median CSS in the IDC-P-present group was 18.2 versus 45.6 months in the IDC-P-absent group (HR 2.67; 95% CI 1.18 to 6.06; P = 0.019). Docetaxel was administered to 36 patients with IDC-P and 10 patients without IDC-P, with a median CSS of 20.5 versus 53.2 months, respectively (HR 2.98; 95% CI 1.02 to 8.64; P = 0.044). Multivariate analysis demonstrated that the presence of IDC-P and docetaxel were independent prognostic factors for CSS (P = 0.026 and 0.005, respectively) and overall survival (OS) (P = 0.029 and 0.001, respectively).Conclusion: The presence of IDC-P is an independent prognostic factor in CRPC patients with distant metastases and IDC-P in needle biopsies at the time of initial diagnosis. Docetaxel may prolong CSS and OS in CRPC patients with distant metastases and IDC-P in needle biopsies at the time of initial diagnosis. [ABSTRACT FROM AUTHOR]

Background: Some clinicopathological variables are known to influence the survival of patients with advanced gastric cancer. A comprehensive model based on these factors is needed for prediction of an individual’s survival and appropriate patient counseling.Methods: A nomogram for predicting 1-year survival in patients with advanced gastric cancer in the palliative chemotherapy setting was developed using clinicopathological data from 949 patients with unresectable or metastatic gastric cancer who had received first-line doublet cytotoxic chemotherapy from 2001 to 2006 at the National Cancer Center, Korea (Baseline Nomogram). For 836 patients whose initial response to chemotherapy is known, another nomogram (ChemoResponse-based Nomogram) was constructed using the response to chemotherapy as additional variable. Nomogram performance in terms of discrimination and calibration ability was evaluated using the C statistic and Hosmer-Lemeshow-type χ2 statistics.Results: Two different nomograms were developed and subjected to internal validation. The baseline nomogram incorporated 13 baseline clinicopathological variables, whereas the chemoresponse-based nomogram was composed of 11 variables including initial response to chemotherapy. Internal validation revealed good performance of the two nomograms in discrimination: C statistics = 0.656 (95% confidence interval, 0.628-0.673) for the baseline and 0.718 (95% confidence interval, 0.694-0.741) for the chemoresponse-based nomogram, which showed significantly better discrimination performance than the baseline nomogram (Z statistics = 3.74, p < 0.01).Conclusion: This study suggests that individual 1-year survival probability of patients receiving first-line doublet cytotoxic chemotherapy for advanced gastric cancer can be reliably predicted by a nomogram-based method incorporating clinicopathological variables and initial response to chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Radiation dose escalation for prostate cancer improves biochemical control but is limited by toxicity. Magnetic resonance spectroscopic imaging (MRSI) can define dominant intraprostatic lesions (DIL). This phase I study evaluated dose escalation to MRSI-defined DIL using high-dose-rate (HDR) brachytherapy. Material and methods: Enrollment was closed early due to low accrual. Ten patients with prostate cancer (T2a-3b, Gleason 6-9, PSA < 20) underwent pre-treatment MRSI, and eight patients had one to three DIL identified. The eight enrolled patients received external beam radiation therapy to 45 Gy and HDR brachytherapy boost to the prostate of 19 Gy in 2 fractions. MRSI images were registered to planning CT images and DIL dose-escalated up to 150% of prescription dose while maintaining normal tissue constraints. The primary endpoint was genitourinary (GU) toxicity. Results: The median total DIL volume was 1.31 ml (range, 0.67-6.33 ml). Median DIL boost was 130% of prescription dose (range, 110-150%). Median urethra V120 was 0.15 ml (range, 0-0.4 ml) and median rectum V75 was 0.74 ml (range, 0.1-1.0 ml). Three patients had acute grade 2 GU toxicity, and two patients had late grade 2 GU toxicity. No patients had grade 2 or higher gastrointestinal toxicity, and no grade 3 or higher toxicities were noted. There were no biochemical failures with median follow-up of 4.9 years (range, 2-8.5 years). Conclusions: Dose escalation to MRSI-defined DIL is feasible. Toxicity was low but incompletely assessed due to limited patients' enrollment. [ABSTRACT FROM AUTHOR]

Purpose: There is limited data to support the use of hypofractionated external beam radiation (HypoF) in combination with high-dose-rate brachytherapy (HDR). We report our quality of life (QOL) outcomes when treating intermediate and high-risk prostate cancer patients with external beam radiation (EBRT) plus HDR. Material and methods: The charts of 54 patients with localized adenocarcinoma of the prostate treated with standard fractionation (SF) or HypoF EBRT plus HDR boost at a single institution between 2012 and 2015 were reviewed. All patients completed the American Urological Association Symptom Score (AUASS) and Expanded Prostate Index for Prostate Cancer - Clinical Practice (EPIC-CP) quality of life assessments prior to treatment and completed at least one follow-up survey. Linear mixed models were performed to test for significant changes and differences in each outcome over time. Results: There was no significant difference in AUA score (p = 0.98), incontinence (urge) and urinary irritation/ obstruction scores (p = 0.81 and p = 0.62, respectively), and bowel QOL (p = 0.97) between the two dosing groups over time or at any discrete time point. For both groups, AUA scores peaked at 0-2 months before improving. Likewise, sexual function, vitality score, and QOL scores were also not significantly different between the dose groups over time (p = 0.59, p = 0.37, and p = 0.71, respectively). All QOL categories, except sexual function, trended toward baseline with increasing time from intervention. Conclusions: Our study suggests HypoF EBRT can be delivered in combination with HDR for patients with ntermediate-risk and high-risk adenocarcinoma of the prostate without increasing toxicity compared to SF with an HDR boost. [ABSTRACT FROM AUTHOR]

Motivated by the capabilities of modern radiotherapy techniques and by the recent developments of functional imaging techniques, dose painting by numbers (DPBN) was proposed to treat tumors with heterogeneous biological characteristics. This work studies different DPBN optimization techniques for virtual head and neck tumors assessing tumor response in terms of cell survival and tumor control probability with a previously published tumor response model (TRM). Uniform doses of 2 Gy are redistributed according to the microscopic oxygen distribution and the density distribution of tumor cells in four virtual tumors with different biological characteristics. In addition, two different optimization objective functions are investigated, which: i) minimize tumor cell survival (OFsurv) or; ii) maximize the homogeneity of the density of surviving tumor cells (OFstd). Several adaptive schemes, ranging from single to daily dose optimization, are studied and the treatment response is compared to that of the uniform dose. The results show that the benefit of DPBN treatments depends on the tumor reoxygenation capability, which strongly differed among the set of virtual tumors investigated. The difference between daily (fraction by fraction) and three weekly optimizations (at the beginning of weeks 1, 3 and 4) was found to be small, and higher benefit was observed for the treatments optimized using OFsurv. This in silico study corroborates the hypothesis that DPBN may be beneficial for treatments of tumors which show reoxygenation during treatment, and that a few optimizations may be sufficient to achieve this therapeutic benefit. [ABSTRACT FROM AUTHOR]

Introduction: Radiotherapy can diminish quality of life (QoL) for prostate cancer patients. Our objective was to evaluate the effect of radiotherapy on QoL in men aged 75 years or older treated with radiotherapy for a localized prostate cancer, and to identify predictors of reduced QoL. Patients and methods: We prospectively administered a battery of geriatric (MNA, GDS, Get up and Go Test, CIRS-G, ADL, IADL, MMSE), toxicity (IPSS; IIEF 5), and QoL (QLQ C30) screening tests in 100 elderly patients before and two months after prostate cancer radiotherapy (NCT 02876237). Patients ≥ 75 years undergoing radiotherapy with a curative intent for localized prostate cancer with or without androgen deprivation therapy (ADL) were eligible for study inclusion. Correlations between patient-assessed QoL and tumor characteristics, radiotherapy treatment or CGA parameters were sought using the Fisher or the Mann and Whitney tests. Changes in QoL parameters over time were analyzed using the Wilcoxon signed-rank test. Results: At study entry, scores for IADL impairments were present in 51%, reduced autonomy in activities of daily living in 16%, cognitive impairment found in 20%, depression-related symptoms in 31%, and 66% of patients had significant co-morbidities. Eight percent were judged to be at risk of fall and 2% were found to be undernourished. Severely impaired (IPSS ≥ 20) urinary function was observed in 11.2% and 13.5% of patients before and two months after completion of radiotherapy respectively. Significantly decreased QoL (> 20 points) at two months after treatment was found in 13% of patients and a moderate but clinically relevant reduction (10 to 20 points) in 17% of patients. No tumor characteristic, treatment, or oncogeriatric parameter was predictive of reduced QoL following prostate cancer radiotherapy. Conclusion: Despite sometimes markedly diminished oncogeriatric parameters, prostate cancer radiotherapy was generally well tolerated in these elderly patients. We found no predictive factor to determine which patients would experience impaired quality of life following radiotherapy. [ABSTRACT FROM AUTHOR]