Transitioning from conformal radiotherapy to intensity-modulated radiotherapy after radical prostatectomy: Clinical benefit, oncologic outcomes and incidence of gastrointestinal and urinary toxicities.

AIM: The purpose of this study was to review genitourinary (GU) and gastrointestinal (GI) toxicity associated with high-dose radiotherapy (RT) delivered with 3-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) or volumetric arc therapy (VMAT) following radical prostatectomy (RP). BACKGROUND: RP is a therapeutic option for the management of prostate cancer (PrCa). When assessing postoperative RT techniques for PrCa, the published literature focuses on patients treated with 2-dimensional conventional methods without reflecting the implementation of 3D-CRT, IMRT, or VMAT. MATERIALS AND METHODS: A total of 83 patients were included in this analysis; 30 patients received 3D-CRT, and 53 patients received IMRT/VMAT. Acute and late symptoms of the GU and lower GI tract were retrospectively graded according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer radiation toxicity grading systems. The relapse failure-free rate and overall survival were also evaluated. RESULTS: The rate of acute GU toxicity was 9.4% vs. 13.3% for the IMRT/VMAT and 3D-CRT groups (p = 0.583). The 5-year actuarial rates of late GI toxicity for IMRT/VMAT and 3D-CRT treatments were 1.9% and 6.7%, respectively. The rate of late GU toxicity for the IMRT/VMAT and 3D-CRT treatment groups was 7.5% and 16.6%, respectively (p = 0.199). We found no association between acute or late toxicity and the RT technique in univariate and multivariate analyses. CONCLUSION: Postprostatectomy IMRT/VMAT and 3D-CRT achieved similar morbidity and cancer control outcomes. The clinical benefit of highly conformal techniques in this setting is unclear although formal analysis is needed.

Disparities in cancer-specific and overall survival in black women with endometrial cancer: A Medicare-SEER study.

OBJECTIVES: To examine overall survival (OS) and cancer-specific survival (CSS) for different racial groups of women with surgically staged endometrial cancer by histologic subtype. METHODS: This is a retrospective cohort study of women with stage I-III endometrioid, serous, clear cell, and carcinosarcoma who underwent hysterectomy as primary surgical staging in the 2000-2016 SEER-Medicare database. OS and CSS outcomes were stratified by race (defined as White, Black, Other), stage, and histology. Survival was assessed with descriptive analyses, log-rank tests and unadjusted and adjusted multivariable cox regression models. RESULTS: Of the 24,142 women identified, 85.5% were White, 8.5% Black, and 6% other races. Receipt of adjuvant therapy differed only for stage III endometrioid: Black women were less likely to receive adjuvant treatment after hysterectomy (61.2% vs. 70.1% White, p = 0.03). For stage I, Black women had worse CSS for all histologies other than clear cell in unadjusted and adjusted analyses. For stage II, Black women had worse CSS for endometrioid histology in unadjusted analyses and similar OS. For stage III, Black women with endometrioid carcinoma had worse CSS and OS in unadjusted analyses, but no significant difference in CSS in adjusted analyses. "Other" race showed improved OS for Stage I endometrioid adenocarcinoma without significant differences in outcomes when compared to White women. CONCLUSION: Across histologies other than clear cell, Black women diagnosed with stage I endometrial cancer had consistently worse CSS, despite similar receipt of adjuvant therapy. Differences in CSS and OS at higher stages disappeared once accounting for treatment disparities.

A brief review and case report of urothelial carcinoma and metachronous leiomyosarcoma of the bladder at the same anatomic region.

One patient with bladder leiomyosarcoma and urothelial carcinoma is very rare. Only 10 cases have been reported in the literature. A 70-year-old patient was admitted due to bladder tumor. Two TURBTs were performed confirming the patient was free of tumor, and pathology reported low-grade urothelial carcinoma. Three years later, a tumor was also found on the right anterolateral wall of urinary bladder and was diagnosed as leiomyosarcoma by pathological examination. Radical cystectomy was performed. With 45 months follow-up, the patient has no recurrence. Two malignancies in the same anatomic region at different time has never been reported to date.

BRCA testing and testing results among women 18-65 years old.

Since the 1990 s discovery of BRCA1 and BRCA2 pathogenic variants in breast or ovarian cancer patients, genetic testing has been recommended as part of a targeted, individualized approach for cancer prevention and treatment in eligible individuals. The aim of this study was to assess trends in BRCA test rates and results among adult women aged 18 to 65 in the US between 2007 and 2017. Using Clinformatics© Data Mart (CDM) Electronic Health Records, we included 223,211 women 18-65 years old with documented BRCA testing results from 1/1/2007-9/30/2017. Positive results indicated the presence of pathogenic variantss. BRCA test rates increased significantly from 34 per 100,000 women in 2007 to 488 per 100,000 women in 2016 (APC 30.8, 95% confidence interval 26.6-35.1). Documented positive results decreased from 86.1% in 2007 to 78.0% in 2017(APC -0.6, 95% confidence interval -1.4-0.2). From 2007 to 2017, decreasing trends in the rates of documented positive results were observed among all three age groups (18-39, 40-54, and 55-65 years; largest in 40-54 group). In 2015-2017, women with positive test results were less likely to be non-Hispanic Whites, cancer patients, or living in the Northeast or an area with average household income ≥$50,000. Between 2007 and 2017, increasing use of BRCA testing for cancer prevention and treatment occurred, correlating to the observed decreasing documented positive test rate. The utilization of testing and corresponding test results differed significantly across races/ethnicities, suggestive of a divergent application of the same testing criteria.

Merkel cell carcinoma: Epidemiology, disease presentation, and current clinical practice outcomes.

Using the National Cancer Database, we introduce the findings of a retrospective investigation of the largest cohort of cases with Merkel cell carcinoma (N = 20,829). A decreasing proportion of stage I (P = .0004) and stage II (P = .0065) Merkel cell carcinoma among skin cancers was complemented by an increasing proportion of stage III disease (P < .0001). A predominance of non-Hispanic White (96.4%), male (62.6%) patients with a mean age of 74.5 ± 10.8 years and Medicare coverage (73.5%) was observed. Stage I was the most common presenting stage at diagnosis (29.2%), followed by stages II (12.7%), III (11.0%), and IV (3.8%). Most Merkel cell carcinoma tumors grew outside the head and neck (53.4%) and showed a nodular growth pattern (66.0%) but no extracapsular lymph node (90.5%) or lymphovascular involvement (63.8%). Narrow-margin excision and radiation therapy (RT) were used in 75.2% and 56.3% of tumors, respectively. Wide-margin excision lead to improved overall survival (P < .001) versus narrow-margin excision, particularly in stage III (difference in the median overall survival rate [ΔmOS], 23.7 months; P < .001). RT showed a significant OS benefit (P =.006), most pronounced in stage II (ΔmOS, 37.8 months) followed by stage I (ΔmOS, 16.1 months; P < .001). The survival benefit with primary-site RT (ΔmOS, 24.0 months) was higher than that with primary-site/lymph node RT (ΔmOS, 5.2 months; P < .001). Wide-margin excision independently predicted improved OS (hazard ratio, 0.577; 95% CI, 0.403-0.826; P = .003) versus narrow-margin excision and RT predicted better OS (hazard ratio, 0.608; 95% CI, 0.424-0.873; P = .007) versus no RT on multivariable analysis.

Interrater agreement of contouring of the neurovascular bundles and internal pudendal arteries in neurovascular-sparing magnetic resonance-guided radiotherapy for localized prostate cancer.

BACKGROUND AND PURPOSE: Radiation damage to neural and vascular tissue, such as the neurovascular bundles (NVBs) and internal pudendal arteries (IPAs), during radiotherapy for prostate cancer (PCa) may cause erectile dysfunction. Neurovascular-sparing magnetic resonance-guided adaptive radiotherapy (MRgRT) aims to preserve erectile function after treatment. However, the NVBs and IPAs are not routinely contoured in current radiotherapy practice. Before neurovascular-sparing MRgRT for PCa can be implemented, the interrater agreement of the contouring of the NVBs and IPAs on pre-treatment MRI needs to be assessed. MATERIALS AND METHODS: Four radiation oncologists independently contoured the prostate, NVB, and IPA in an unselected consecutive series of 15 PCa patients, on pre-treatment MRI. Dice similarity coefficients (DSCs) for pairwise interrater agreement of contours were calculated. Additionally, the DCS of a subset of the inferior half of the NVB contours (i.e. approximately prostate midgland to apex level) was calculated. RESULTS: Median overall interrater DSC for the left and right NVB was 0.60 (IQR: 0.54 - 0.68) and 0.61 (IQR: 0.53 - 0.69) respectively and for the left and right IPA 0.59 (IQR: 0.53 - 0.64) and 0.59 (IQR: 0.52 - 0.64) respectively. Median overall interrater DSC for the inferior half of the left NVB was 0.67 (IQR: 0.58 - 0.74) and 0.67 (IQR: 0.61 - 0.71) for the right NVB. CONCLUSION: We found that the interrater agreement for the contouring of the NVB and IPA improved with enhancement of the MRI sequence as well as further training of the raters. The agreement was best in the subset of the inferior half of the NVB, where a good agreement is clinically most relevant for neurovascular-sparing MRgRT for PCa.

Irradiation of localized prostate cancer in the elderly: A systematic literature review.

Purpose: To analyze the literature that addresses radiation therapy for intermediate and high-risk prostate cancer (PC) in the elderly. Patients and methods: A PubMed literature search was conducted including articles from 01/01/2000 to 30/06/21, with the following keywords: PC, radiotherapy/brachytherapy and elderly. The analysis mainly focused on the issue of under-treatment in the elderly and the benefit/risk balance of irradiation. Results: Of the 176 references analyzed, 24 matched the selection criteria. The definition of "elderly patient" varied from 70 to 80 years. The analysis was impacted by the inhomogeneous primary end points used in each cohort. Age was often an obstacle to radical treatment, with a subsequent risk of under-treatment, particularly in patients with a poorer prognosis. However, comparable elderly oncological outcomes were compared to younger patients, both with external beam radiotherapy alone or combined with brachytherapy boost. Late toxicity rates are low and most often comparable to younger populations. However, a urinary over- toxicity was observed in the super-elderly (>80 years) after brachytherapy boost. The use of ADT should be considered in light of comorbidities, and may even be deleterious in some patients. Conclusion: Due to the increase in life expectancy, the management of PC in the elderly is a challenge for patients, clinicians and health insurance payers. Except for unfit men, elderly patients remain candidates for optimal curative treatment (i.e. regardless of age) after oncogeriatric assessment. More solid data from prospective trials conducted specially in this population will provide better guidance in our daily clinical practice.

Whole Brain Irradiation or Stereotactic RadioSurgery for five or more brain metastases (WHOBI-STER): A prospective comparative study of neurocognitive outcomes, level of autonomy in daily activities and quality of life.

AIMS: To evaluate neurocognitive performance, daily activity and quality of life (QoL), other than usual oncologic outcomes, among patients with brain metastasis ≥5 (MBM) from solid tumors treated with Stereotactic Brain Irradiation (SBI) or Whole Brain Irradiation (WBI). METHODS: This multicentric randomized controlled trial will involve the enrollment of 100 patients (50 for each arm) with MBM ≥ 5, age ≥ 18 years, Karnofsky Performance Status (KPS) ≥ 70, life expectancy > 3 months, known primary tumor, with controlled or controllable extracranial disease, baseline Montreal Cognitive Assessment (MoCA) score ≥ 20/30, Barthel Activities of Daily Living score ≥ 90/100, to be submitted to SBI by LINAC with monoisocentric technique and non-coplanar arcs (experimental arm) or to WBI (control arm). The primary endpoints are neurocognitive performance, QoL and autonomy in daily-life activities variations, the first one assessed by MoCa Score and Hopkins Verbal Learning Test-Revised, the second one through the EORTC QLQ-C15-PAL and QLQ-BN-20 questionnaires, the third one through the Barthel Index, respectively. The secondary endpoints are time to intracranial failure, overall survival, retreatment rate, acute and late toxicities, changing of KPS. It will be considered significant a statistical difference of at least 30% between the two arms (statistical power of 80% with a significance level of 95%). DISCUSSION: Several studies debate what is the decisive factor accountable for the development of neurocognitive decay among patients undergoing brain irradiation for MBM: radiation effect on clinically healthy brain tissue or intracranial tumor burden? The answer to this question may come from the recent technological advancement that allows, in a context of a significant time saving, improved patient comfort and minimizing radiation dose to off-target brain, a selective treatment of MBM simultaneously, otherwise attackable only by WBI. The achievement of a local control rate comparable to that obtained with WBI remains the fundamental prerequisite. TRIAL REGISTRATION: NCT number: NCT04891471.

High-dose-rate brachytherapy boost for elderly patients with intermediate to high-risk prostate cancer: 5-year clinical outcome of the PROSTAGE cohort.

Purpose: To analyze the oncological outcome in elderly (>70 years) prostate cancer after high-dose rate brachytherapy (HDB) boost. Materials/methods: In this retrospective study, patients with intermediate (IR) and high-risk (HR) prostate cancer underwent external beam radiation therapy (EBRT) followed by HDB boost with/without androgen deprivation therapy (ADT). The impact of age (≤70y vs. > 70y) was investigated. Oncological outcome focused on biochemical relapse-free survival (bRFS), cause-specific (CSS) and overall survival (OS). Late genito-urinary (GU) and gastro-intestinal (GI) toxicities were investigated. Results: From 07/08 to 01/22, 518 pts received a HDB boost, and 380 were analyzed (≤70y:177pts [46.6%] vs. > 70y:203pts [53.4%]). Regarding NCCN classification, 98 pts (≤70y: 53pts; >70y: 45pts; p = 0.107) and 282 pts (≤70y: 124pts; >70y: 158pts; p = NS) were IR and HR pts respectively. Median EBRT dose was 46 Gy [37.5-46] in 23 fractions [14-25]. HDB boost delivered a single fraction of 14/15 Gy (79%). ADT was used in 302 pts (≤70y: 130pts; >70y: 172pts; p = 0.01). With MFU of 72.6 months [67-83] for the whole cohort, 5-y bRFS, 5-y CSS and 5-y OS were 88% [85-92], 99% [97-100] and 94% [92-97] respectively; there was no statistical difference between the two age groups except for 5-y CSS (p = 0.05). Late GU and GI toxicity rates were 32.4% (G ≥ 3 7.3%) and 10.1% (no G3) respectively. Conclusions: For IR and HR prostate cancers, HDB boost leads to high rates of disease control with few late G ≥ 3 GU/GI toxicities. For elderly pts, HDB boost remains warranted mainly in HR pts, while competing comorbidity factors influence OS.

Single fraction of HDR brachytherapy for prostate cancer: Results of the SiFEPI phase II prospective trial.

Purpose: To report the results of the Single Fraction Early Prostate Irradiation (SiFEPI) phase 2 prospective trial. Materials/Methods: The SiFEPI trial (NCT02104362) evaluated a single fraction of high-dose rate brachytherapy (HDB) for low- (LR) and favorable-intermediate (FIR) risk prostate cancers. After rectal spacer placement, a single fraction of 20 Gy was delivered to the prostate. Oncological outcome (biochemical (bRFS) and local (lRFS) relapses, disease-free (DFS) and overall (OS) survivals and toxicity (acute/late genito-urinary (GU), gastro-intestinal (GI) and sexual (S) toxicities were investigated. Results: From 03/2014 to 10/2017, 35 pts were enrolled, of whom 33 were evaluable. With a median age of 66 y [46-79], 25 (76 %) and 8 (24 %) pts were LR and FIR respectively. With a MFU of 72.8 months [64-86], 6y-bRFS, lRFS and mRFS were 62 % [45-85], 61 % [44-85] and 93 % [85-100] respectively while 6y-DFS, CSS and OS were 54 % [37-77], 100 % and 89 % [77-100] respectively. Late GU, GI and S toxicities were observed in 11 pts (33 %;18G1), 4 pts (12 %;4G1) and 7 pts (21 %;1G1,5G2,1G3) respectively. Biochemical relapse (BR) was observed in 11 pts (33 %;7LR,4FIR) with a median time interval between HDB and BR of 51 months [24-69]. Nine of these pts (82 %) presented a histologically proven isolated local recurrence. Conclusions: Long-term results of the SiFEPI trial show that a single fraction of 20 Gy leads to sub-optimal biochemical control for LR/FIR prostate cancers. The late GU and GI toxicity profile is encouraging, leading to consideration of HDB as a safe irradiation technique.

Topical treatments for early-stage mycosis fungoides using Grading Recommendations Assessment, Development and Evaluation (GRADE) criteria: A systematic review.

BACKGROUND: Mycosis fungoides (MF) is a cutaneous lymphoma; most patients present with early, skin-limited disease and are managed by dermatologists. OBJECTIVE: The purpose of this study was to systematically review and assess the evidence on topical treatments for early-stage (IA, IB, IIA) MF. METHODS: We performed a literature search via MEDLINE, Embase, Web of Science, and Cochrane databases. Grading Recommendations Assessment, Development and Evaluation (GRADE) criteria were used to assess the certainty of the data. RESULTS: Two searches yielded 1252 references; 26 met the inclusion criteria and included literature on nitrogen mustard, retinoids, corticosteroids, carmustine, fluorouracil, methotrexate-laurocapram, hexadecylphosphocholine, peldesine, ingenol mebutate, topical methotrexate with oxygen flow-assisted LP3 carrier, and resiquimod. Most studies were single intervention, observational series. Nitrogen mustard, with the most published reports, was effective with 12%-82% early-stage MF patients (total n > 1000) achieving complete remission (CR) (low certainty evidence). Clinical CR was achieved among 10%-60% treated with topical retinoids (low certainty evidence). Two moderate-sized retrospective case series on topical steroids had 18%-63% CR (low certainty evidence). Only single studies were available for the other therapies. CONCLUSIONS: For most outcomes of interest, the GRADE certainty for topical therapies for early-stage MF was low. Further randomized controlled trials and inclusion of quality of life indicators are needed.

Early outcomes of high-dose-rate brachytherapy combined with ultra-hypofractionated radiation in higher-risk prostate cancer.

PURPOSE: This study evaluated outcomes associated with a high-dose-rate (HDR) brachytherapy boost combined with stereotactic body radiation therapy (SBRT) for patients with higher-risk localized prostate cancer. MATERIALS AND METHODS: We identified 101 patients with National Comprehensive Cancer Network high-risk, unfavorable intermediate-risk, or favorable intermediate-risk with probable extra-prostatic extension treated with HDR brachytherapy (15 Gy x 1 fraction) followed by SBRT (5 Gy x 5 daily fractions to the prostate and/or seminal vesicles and/or pelvic lymph nodes). Androgen deprivation therapy was used in 55.4% of all patients (90% of high-risk, 33% of intermediate-risk). Toxicities according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0 and International Prostate Symptom Scores were prospectively documented at each followup visit. Biochemical relapse was defined as PSA nadir +2ng/mL. RESULTS: The median follow-up time after SBRT was 24.1 months. No grade ≥3 toxicities were observed. The incidence of acute and late grade 2 gastrointestinal toxicities was both 0.99%. Acute and late grade 2 genitourinary (GU) toxicities were observed in 5.9% and 9.9%, respectively. Median time to a grade 2 GU toxicity was 6 months with a 14% 2-year actuarial rate of grade 2 GU toxicity. Median International Prostate Symptom Scores at 24 months was not significantly different than baseline (6 vs. 5; p = 0.24). Inclusion of pelvic lymph nodes and absence of a rectal spacer were significantly associated with more frequent grade ≥1 GU toxicity, but not grade ≥2 GU or gastrointestinal toxicity. The 2-year biochemical relapse free survival was 97%. CONCLUSIONS: HDR brachytherapy combined with SBRT was associated with a favorable early toxicity profile and encouraging cancer control outcomes.

High-dose rate brachytherapy in localized penile cancer: 5-Year clinical outcome analysis.

PURPOSE: To analyze the oncological outcome and toxicity profile after conservative treatment based on multicatheter interstitial high-dose rate brachytherapy (MHB) for patients presenting a localized penile cancer. MATERIALS AND METHODS: Patients with histologically proven, non-metastatic (T1-T2 N0-N2 M0) localized penile cancer were treated with MHB. Needles were placed under general anesthesia into the target volume using a dedicated template. Treatment planning was performed using a post-implant CT-scan to deliver 35 Gy or 39 Gy (9f, 5d) for adjuvant or definitive treatment respectively. Five-year oncological outcome was evaluated with local relapse-free (LRFS), regional relapse-free (RRFS), and metastasis-free survival (MFS), specific (SS) and overall survival (OS). In pre-treatment and follow-up consultations, skin, urinary and sexual toxicities were investigated using CTCAEv4.0 classification, International Prostate Symptom Score (IPSS) and International Index of Erectile Function 5-items (IIEF-5). Dosimetry data were also analyzed. RESULTS: From 03/2006 to 05/2020, with a median follow-up of 72.4 months [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], 29 pts, mainly T1 (75.9%) and N0 (89.7%), underwent MHB. Eleven (38%) and 18 pts (62%) received MHB as adjuvant or definitive treatment respectively. Five-year LRFS, RRFS, MFS, SS and OS were 82%, 82%, 89%, 88% and 73% respectively. Six patients (20.7%) experienced local relapse and underwent salvage penectomy leading to a penile preservation rate of 79.3%. Acute skin toxicity was reported 1 month after MHB, with 28% G1, 66% G2 and 6% G3. Late skin complications were telangiectasia for 5 pts (17%) and necrosis for 3 pts (10.3% requiring hyperbaric oxygen therapy). Comparing pre- and post-treatment status, no significant change was observed for skin appearance, IPSS and IIEF-5. CONCLUSION: MHB represents an efficient first line conservative treatment option for early penile cancers. Oncological outcome and late toxicity profile appear encouraging. However, larger-scale cohorts with longer follow-up are needed to more accurately precise the features of the best candidate to MHB.

Development of small-molecule tropomyosin receptor kinase (TRK) inhibitors for NTRK fusion cancers.

Tropomyosin receptor kinase A, B and C (TRKA, TRKB and TRKC), which are well-known members of the cell surface receptor tyrosine kinase (RTK) family, are encoded by the neurotrophic receptor tyrosine kinase 1, 2 and 3 (NTRK1, NTRK2 and NTRK3) genes, respectively. TRKs can regulate cell proliferation, differentiation and even apoptosis through the RAS/MAPKs, PI3K/AKT and PLCγ pathways. Gene fusions involving NTRK act as oncogenic drivers of a broad diversity of adult and pediatric tumors, and TRKs have become promising antitumor targets. Therefore, achieving a comprehensive understanding of TRKs and relevant TRK inhibitors should be urgently pursued for the further development of novel TRK inhibitors for potential clinical applications. This review focuses on summarizing the biological functions of TRKs and NTRK fusion proteins, the development of small-molecule TRK inhibitors with different chemotypes and their activity and selectivity, and the potential therapeutic applications of these inhibitors for future cancer drug discovery efforts.

Pembrolizumab plus platinum-based chemotherapy for unfavorable cancer of unknown primary site: Case report.

INTRODUCTION: We report a case of sustained complete response in unfavorable cancer of unknown primary site (CUP) successfully treated with chemotherapy combining pembrolizumab, pemetrexed and platinum. CASE PRESENTATION: A 66-year-old man was presented with weight loss and cough for 3 months. Contrast-enhanced computed tomography (CT) confirmed a mass in the superior anterior mediastinum and multiple enlarged mediastinal and axillary lymph nodes. Positron emission tomography-CT (PET-CT) showed abnormal uptake in the corresponding lesions. Histopathological analysis of the left axillary nodule revealed poorly differentiated adenocarcinoma. Immunohistochemistry showed the tumor cells were positive for cytokeratin 7 and thyroid transcription factor-1 and negative for cytokeratin 20. Thus, the patient was diagnosed as poorly differentiated adenocarcinoma of unknown primary, and treated as non-small-cell lung cancer. Additional genetic testing revealed the patient was negative for EGFR, ALK fluorescence in situ hybridization, ROS1, BRAF, and PD-L1 22C3 IHC with Tumor Proportion Score (TPS) was less than 1%. The patient received six cycles of pembrolizumab, platinum, and pemetrexed intravenously. Cisplatin was switched to carboplatin because of cisplatin nephrotoxicity in one course. PET-CT after six cycles showed all lesions disappeared; complete response was considered to have been achieved. Maintenance therapy of pembrolizumab and pemetrexed has been continued for 6 months after the induction therapies to prevent progressive disease. Complete response has been maintained. DISCUSSION: Chemotherapy with pembrolizumab, platinum and pemetrexed could be valuable for treating unfavorable CUP. CONCLUSION: Chemotherapy with pembrolizumab, platinum, and pemetrexed helped achieved sustained complete response in a patient with unfavorable CUP.

Limb-salvage surgery offers better five-year survival rate than amputation in patients with limb osteosarcoma treated with neoadjuvant chemotherapy. A systematic review and meta-analysis.

BACKGROUND: Osteosarcoma is the most common primary bone sarcoma. Currently, the main treatment option for high-grade osteosarcomas is neoadjuvant chemotherapy, followed by surgical resection of the lesion and adjuvant chemotherapy. Limb salvage surgery (LSS) and amputation are the main surgical techniques; however, controversy still exists concerning the best surgical method. Our meta-analysis compared the effectiveness of LSS and amputation combined with neoadjuvant chemotherapy in patients with limb osteosarcoma, in terms of 5-year overall survival (OS), 5-year disease-free survival (DFS) and local recurrence rate. METHODS: Following the established methodology of PRISMA guidelines, a literature search was conducted in PubMed, Cochrane, Google Scholar from 1975 until January 2020. Two independent reviewers evaluated the study quality based on the Newcastle-Ottawa scale. Odds ratio and 95% confidence interval of the OS, DFS and local recurrence rate were calculated. RESULTS: Thirteen studies were finally included with a total of 2884 patients; 1986 patients undergone LSS and 898 amputations. Five-year overall survival was almost 2-fold in patients treated with LSS than those treated with amputation (OR: 1.99; 95% CI: 1.35-2.93; I2 = 74%, p < 0.001). No difference was found in 5-year DFS between LSS patients and amputees (OR: 1.24; 95% CI: 0.55-2.79; I2 = 67%, p = 0.01). The odds of local recurrence was numerically higher in LSS compared to amputation but not statistically significant (OR: 2.29; 95% CI: 0.95-5.53; I2 = 47%, p = 0.05). However, the included studies did not clearly define differences in the stages of patients of the two groups. CONCLUSION: Our study demonstrated that in patients with limb osteosarcoma treated with neoadjuvant chemotherapy, LSS is associated with a higher 5-year overall survival and the odds of local recurrence may be increased but these results should be interpreted with caution due to high heterogeneity.

Multi-disciplinary and shared decision-making approach in the management of organ-confined prostate cancer.

Decision-making in the management of organ-confined prostate cancer is complex as it is based on multi-factorial considerations. It is complicated by a multitude of issues, which are related to the patient, treatment, disease, availability of equipment(s), expertise, and physicians. Combination of all these factors play a major role in the decision-making process and provide for an interactive decision-making preferably in the multi-disciplinary team (MDT) meeting. MDT decisions are comprehensive and are often based on all factors including patients' biological status, disease and its aggressiveness, and physician and centres' expertise. However, one important and often under rated factor is patient-related factors. There is considerable evidence that patients and physicians have different goals for treatment and physicians' understanding of their own patients' preferences is not accurate. Several patient-related key factors have been identified such as age, religious beliefs, sexual health, educational background, and cognitive impairment. We have focused on these areas and highlight some key factors that need to be taken considered whilst counselling a patient and understanding his choice of treatment, which might not always be match with the clinicians' recommendation.

Detection of KIT mutations in core binding factor acute myeloid leukemia.

We have investigated the frequency and the effect of KIT mutations on the outcome of patients with CBF-AML. 69 patients (34 pediatrics and 35 adults) with CBF-AML were enrolled in the study. The frequency of KIT mutations was higher in adults compared to pediatrics (22.9% and 14.7%, p = 0.38) respectively. Leukocytosis ≥ 20 × 109 /L was significantly associated with pediatrics compared to adults. t(8;21)(q22;22) was significantly associated with thrombocytopenia in adults. We conclude that no significant difference is found between KIT mutated and unmutated CBF-AML in adults and pediatrics. Children with CBF-AML present with leukocytosis. t(8;21) is associated with thrombocytopenia.

Intravoxel incoherent motion (IVIM) and non-Gaussian diffusion MRI of the lactating breast.

PURPOSE: To investigate the effect of breastfeeding on IVIM and non-Gaussian diffusion MRI in the breast. MATERIALS AND METHODS: An IRB approved prospective study enrolled seventeen volunteers (12 in lactation and 5 with post-weaning, range 31-43 years; mean 35.4 years). IVIM (fIVIM and D*) and non-Gaussian diffusion (ADC0 and K) parameters using 16 b values, plus synthetic apparent diffusion coefficients (sADCs) from 2 key b values (b = 200 and 1500 s/mm2) were calculated using regions of interest. ADC0 maps of the whole breast were generated and their contrast patterns were evaluated by two independent readers using retroareolar and segmental semi-quantitative scores. To compare the diffusion and IVIM parameters, Wilcoxon signed rank tests were used between pre- and post-breastfeeding and Mann-Whitney tests were used between post-weaning and pre- or post-breastfeeding. RESULTS: ADC0 and sADC values significantly decreased post-breastfeeding (1.90 vs. 1.72 × 10-3 mm2/s, P < 0.001 and 1.39 vs. 1.25 × 10-3 mm2/s, P < 0.001) while K values significantly increased (0.33 vs. 0.44, P < 0.05). fIVIM values significantly increased after breastfeeding (1.97 vs. 2.97%, P < 0.01). No significant difference was found in D* values. There was significant heterogeneity in ADC0 maps post-breastfeeding, both in retroareolar and segmental scores (P < 0.0001 and =0.0001). CONCLUSION: IVIM and non-Gaussian diffusion parameters significantly changed between pre- and post-breastfeeding status, and care needs to be taken in interpreting diffusion-weighted imaging (DWI) data in lactating breasts.

Methodology for tissue sample collection within a translational sub-study of the CHHiP trial (CRUK/06/016), a large randomised phase III trial in localised prostate cancer.

BACKGROUND: This article presents the methodology for tissue sample collection in Trans-CHHiP, the main translational study within the CHHiP (Conventional or Hypofractionated High dose intensity modulated radiotherapy in Prostate cancer, ISRCTN 97182923) trial. The CHHiP trial randomised 3216 men with localised prostate cancer to 3 different radiotherapy fractionation schedules. Trans-CHHiP aims to identify biomarkers of fraction sensitivity. METHODS: We outline the process of tissue collection, including central review by a study-specific specialist uropathologist and comparison of the centrally-assigned Gleason grade group with that assigned by the recruiting-centre pathologist. RESULTS: 2047 patients provided tissue from 107 pathology departments between August 2012 and April 2014. A highly motivated Clinical Trials Unit chasing samples and a central Trans-CHHiP group that regularly reviewed progress were important for successful sample collection. Agreement in Gleason grade group assigned by the recruiting centre pathologist and the central study-specific uropathologist occurred in 886 out of 1854 (47.8%) cases. Key lessons learned were the need for prospective consent for tissue collection when recruiting patients to the main trial, and the importance of Material Transfer Agreement (MTA) integration into the initial trial site agreement. CONCLUSIONS: This methodology enabled collection of 2047 patient samples from a large randomised radiotherapy trial. Central pathological review is important to minimise subjectivity in Gleason grade grouping and the impact of grade shift.