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Highlights • The main aim of MBM treatment is to palliate neurological symptoms and to maintain an adequate QoL. • SRT could be the “new standard” over WBI in the management of MBM patients. • Neurocognitive functions could deteriorate more after WBI than after SRT., 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.

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.

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., Graphical abstract This review summarized the biological structure and function of tropomyosin receptor kinases (TRKs), as well as neurotrophic receptor tyrosine kinase (NTRK) fusion proteins. The discovery and development of typical TRK inhibitors were discussed by concentrating on their different chemotypes, activity, selectivity and cocrystal structures.Image 1

Highlights • We experienced a case of small intestinal perforation caused by intestinal Burkitt lymphoma. • Pretreatment BL may present with bowel perforation. • This is the first report of such a case., Introduction and importance Small intestinal perforation in patients with Burkitt lymphoma is extremely rare. We present the first report of such a case. Case presentation A 53-year-old woman was admitted with abdominal pain and vomiting. Abdominal examination revealed rigidity and tenderness in the upper abdomen. Computed tomography scan showed thickening of the wall of the jejunum, intra-abdominal free gas, and ascites; the patient was diagnosed with small intestinal perforation, and underwent emergency surgery on the same day. Laparoscopic findings were a 50 mm jejunal perforation and perforation in the transverse mesocolon. A partial jejunal resection of the perforated area, partial transverse colectomy, temporary colostomy, and intra-abdominal drainage were performed. Histological examination showed diffuse infiltration of medium-sized atypical lymphocytes in the perforated area, exhibiting a “starry sky” appearance. Immunostaining results showed that the atypical lymphocytes were CD20 and virtually 100% Ki-67 positive, and CD56, CD30, and EBER negative. The lesion was identified as Burkitt lymphoma (BL). The postoperative course was favorable. On postoperative day 18 the patient began chemotherapy through the hematology department. Currently, the patient is in remission. Clinical discussion The majority of the malignant lymphomas occurring in the digestive tract are identified in the stomach; over 90% are B-cell lymphomas and mucosa-associated lymphoid tissue lymphoma Nakamura et al. BL originating from the small intestine accounts for only about 9%. Conclusion The incidence of BL in the small intestine is low. Pretreatment BL can lead to bowel perforation. Prompt involvement of the hemato-oncologist after definitive diagnosis, and commencing chemotherapy as early as possible after surgery, are thought to improve prognosis.

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., Highlights • The prognosis of patients with unfavorable CUP remains poor. • Pembrolizumab's addition to standard chemotherapy resulted in significantly longer overall survival for patients with NSCLC. • Chemotherapy with pembrolizumab, platinum, and pemetrexed helped achieved sustained complete response in a patient with unfavorable CUP.

Background Recently, the distinction between left- and right-sided colon cancer (LCC and RCC) has been brought into focus. RCC is associated with an inferior overall survival and progression-free survival. We aimed to perform a detailed analysis of the diversity of extracellular vesicles (EV) between LCC and RCC using quantitative proteomics and to identify for new diagnostic and prognostic biomarkers. Methods We isolated EVs from patients with LCC, RCC and healthy volunteers, and treated colorectal cancer cell line with serum-derived EVs. We then performed a quantitative proteomics analysis of the serum-derived EVs and cell line treated with EVs. Proteomic data are available via ProteomeXchange with the identifiers PXD012283 and PXD012304. In addition, we assessed the performance of EV SPARC and LRG1 as diagnosis and prognosis biomarkers in colon cancer. Findings The expression profile of the serum EV proteome in patients with RCC was different from that of patients with LCC. Serum-derived EVs in RCC promoted cellular mobility more significantly than EVs derived from LCC. EV SPARC and LRG1 expression levels demonstrated area under the receiver-operating characteristic curve values of 0.95 and 0.93 for discriminating patients with colon cancer from healthy controls. Moreover, the expression levels of SPARC and LRG1 correlated with tumour sidedness and were predictive of tumour recurrence. Interpretation We identified differences in EV protein profiles between LCC and RCC. Serum-derived EVs of RCC may promote metastasis via upregulation of extracellular matrix (ECM)-related proteins, especially SPARC and LRG1, which may serve as diagnosis and prognosis biomarkers in colon cancer.

KSK is a Distinguished Investigator funded by the Beatriz Galindo (senor modality) Program grant given to the University of Granada by the Ministry of Science, Innovation, and Universities of the Spanish Government. We are thankful for the collaboration of the Europa Donna (The European Breast Cancer Coalition) representatives from Belgium Dr Hirsch and Carly, Dr Aleksandrova from Bulgaria, Dr Moldovanova from Russia, Dr Skjoldborg Hansen from Denmark, Dr Egypt from Estonia, Dr Niemi from Finland, Dr Debiais from France, Dr Sartataviciene from Lithuania, Dr Fischbach from Luxembourg, Dr Barilaro from Monaco, Dr Mellem from Norway, Dr Brankovic-Magica from Serbia, Dr Spanic from Slovenia, Dr Bergsten from Sweden, Dr Corbat from Switzerland, Dr Sprengers from the Netherlands, Dr Spittle from the UK, Dr Maistruck from Ukraine and Europa Donna from Portugal. And we would also like to thank Dr Isabel Rubio (EUSOMA and ESSO President) in Spain, Dr Verhoeven at the Breast Centre Voorkempen in Belgium, Dr Ejlertsen, Dr Bohl and Dr Valvere from the Estonian Cancer Society, Dr Espie from the Hopital Saint-Louis in France, Dr Winkler from the Hungarian League against cancer, Dr Zsuzsanna from the University of Szeged in Hungary, Dr Arnardottir from the Landspitali University Hospital in Iceland, Dr. Dillenbourg from the Universite de Liege in Luxembourg, Dr Daly from the University Hospital Waterford in Ireland, Ms Drochon and Dr Goncharenko from the Institute Nacional du Cancer in France, Dr Jenset from the Swedish Breast Cancer Association, Dr Fredriksson from the Karolinska Institutet in Sweden, Dr Ana Andrijevic from the Institute for pulmonary diseases of Vojvodina, Prof Vrancken Peeters from the Dutch Breast Cancer Audit, Dr Verloop and Dr Siesling from IKNL, Prof Ozmen from the Istanbul Florence Nightingale Hospital, Prof Ozaydin from the Turkish Breast Health Society, Dr Lorez from the Swiss Federal Office of Health, the Swiss Cancer League, Dr Mousavi from the Cancer Registry of eastern Switzerland, and Dr Dagmar from the Swiss Office Q-Label. Finally, we are also grateful for the help provided by the Irish Cancer Society, the Norwegian Breast Cancer Association, the MD Anderson Cancer Center in Spain, the Canadian Breast Cancer Network and the Institute of Breast Disease FUCAM in Mexico, the Ministries of Health from Ireland, Georgia, Iceland, Lithuania and Luxembourg., Breast cancer (BC) management care requires an increment in quality. An initiative to improve the BC quality care is registered, and quality indicators (QIs) are studied. We appraised the appearance of QIs and their standards systematically in Spain. A prospective systematic search (Prospero no: CRD42021228867) for clinical pathways and integrated breast cancer care processes was conducted through databases and the World Wide Web in February 2021. Duplicate data extraction was performed with 98% reviewer agreement. Seventy-four QIs (QI per document mean: 11; standard deviation: 10.59) were found in 15 documents. The Catalonian document had the highest number of QIs (n = 30). No QI appeared in all the documents. There were 9/74 QIs covering structure (12.16%), 53/74 covering process (71.62%), and 12/74 covering outcome (16.22%). A total of 22/66 (33.33%) process and outcome QIs did not set a minimum standard of care. QIs related to primary care, patient satisfaction, and shared decision making were deficient. Most of the documents established a BC QI standard for compliance, but the high variability hinders the comparison of outcomes. Establishing a consensus-based set of QIs needs urgent attention., Spanish Government

Background: To develop a modified Fistula Risk Score (FRS) for predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD) based on both FRS and contrast-enhanced computed tomography (CE-CT). Methods: In this multicenter retrospective analysis, we focused on 990 consecutive patients with pancreatoduodenectomy performed at four institutions between 2009 and 2019. The enhanced CT-FRS model initially targeted 26 pre- and intraoperative factors, including CT descriptors, FRS elements and clinical factors, using LASSO-penalized multivariable logistic regression for predicting CR-POPF events in discovery (n = 718) and externally validated (n = 272) datasets. Probabilities generated were further correlated with histologic features of pancreatic stumps in 356 patients. C-indices were analyzed to compare the predictive potential between the original FRS and the CT-FRS. Findings: CR-POPF developed in 112 (15.6%) and 36 (13.2%) patients in discovery and validation datasets, respectively. The final CT-FRS construct, incorporating remnant pancreatic volume (RPV), stump area, fat and atrophy scores by CT, and main pancreatic duct size, offered significantly greater overall predictability than the original FRS in discovery (C-index: 0.825 vs 0.794; p = 0.04) and validation (0.807 vs 0.741; p = 0.05) cohorts. Importantly, it outperformed the FRS in patients at moderate risk levels (FRS: 3–6), showing remarkably improved C-indices (discovery: 0.729 vs 0.626 [p

Highlights • Penile cancer is a rare tumor. • The organ preservation perspective makes the treatment challenging. • For early stage, conservative brachytherapy achieved excellent oncological outcome. • Conservative brachytherapy reported encouraging functional results. • HDR brachytherapy represents an attractive therapeutic option., 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.

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. Keywords: Prostate cancer, Decision-making, Multi-disciplinary team (MDT), Patients’ preferences

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.

Background This study identifies the overall survival status of lung cancer patients with bone metastasis and metastasis patterns. Poor prognostic factors were identified to develop a scoring system for estimating survival period after bone metastasis. Methods A retrospective cohort analysis was performed at Chiang Mai University for the period January 1, 2006 and December 31, 2013. Time-to-event analysis was performed to estimate survival rate. The primary end point was death related to lung cancer. Univariate and multivariate analysis of the prognostic variables was done using the Cox's regression model. The score was derived from the corresponding estimated regression coefficients of significantly poor prognostic factors. Results A total of 505 lung cancer with bone metastasis patients were analyzed. Four hundred two cases (79.6%) were concurrent diagnosis and 103 (20.4%) were subsequent diagnosis. The median survival time of lung cancer after bone metastasis 148 days. Male gender and ECOG 3–4 were significant poor prognostic factors for lung cancer after bone metastasis, with hazard ratios of 1.42 (95% CI 1.17–1.73), and 1.30 (95% CI 1.06–1.60), respectively. Prognosis score was determined using the binary term present/not-present for those factors. The curve from prognostic score summations of 2, 1 and 0 presented a good discrimination of survival expectancy, showing an expected median survival time of approximately 109, 146, and 225 days, respectively. Conclusions Prognostic score is a clinically simple and easy method for estimating life expectancy and for guiding interventions in bone metastasis of lung cancer., Highlights • Median survival time of lung cancer after bone metastasis is 148 days. • Male, and ECOG 3–4 are poor prognosis factors. • Prognostic score is specific to bone metastasis from lung cancer. • Prognostic score can help guide optimizing intervention in specific group.

Highlights • Breastfeeding significantly affects IVIM and non-Gaussian diffusion parameters. • The distribution of ADC0 values becomes more heterogeneous after breastfeeding. • Care needs to be taken in interpreting DWI data in lactating breasts., 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

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. Keywords: CBF-AML, KIT mutations, FLT-3 mutations, HRM analysis

Objectives: To present our experience of managing penile squamous cell carcinoma (SCC) in a tertiary hospital in Singapore and to evaluate the prognostic value of the inflammatory markers neutrophil–lymphocyte ratio (NLR) and lymphocyte–monocyte ratio (LMR). Patients and methods: We reviewed our prospectively maintained Institutional Review Board-approved urological cancer database to identify men treated for penile SCC at our centre between January 2007 and December 2015. For all the patients identified, we collected epidemiological and clinical data. Results: In all, 39 patients were identified who were treated for penile SCC in our centre. The median [interquartile range (IQR)] follow-up was 34 (16.5–66) months. Although very few (23%) of our patients with high-risk clinical node-negative underwent prophylactic inguinal lymph node dissection (ILND), they still had excellent 5-year recurrence-free survival (RFS; 90%) and cancer-specific survival (CSS; 90%). At multivariate analysis, higher N stage was significantly associated with worse RFS and CSS. Patients with a high NLR (≥2.8) had significantly higher T-stage (P = 0.006) and worse CSS (P

Highlights • Machine learning models might be a better analytic approach in cervical cancer prognostic prediction than traditional methods. • Our models can provide multitask predictions, which can estimate the individual probability of overall survival, overall recurrence, and site-specific recurrence as well as RFS and OS times at the same time. • A web-based calculator was developed and externally validated to predict prognosis for cervical cancer., Background Machine learning (ML) has been gradually integrated into oncologic research but seldom applied to predict cervical cancer (CC), and no model has been reported to predict survival and site-specific recurrence simultaneously. Thus, we aimed to develop ML models to predict survival and site-specific recurrence in CC and to guide individual surveillance. Methods We retrospectively collected data on CC patients from 2006 to 2017 in four hospitals. The survival or recurrence predictive value of the variables was analyzed using multivariate Cox, principal component, and K-means clustering analyses. The predictive performances of eight ML models were compared with logistic or Cox models. A novel web-based predictive calculator was developed based on the ML algorithms. Results This study included 5112 women for analysis (268 deaths, 343 recurrences): (1) For site-specific recurrence, larger tumor size was associated with local recurrence, while positive lymph nodes were associated with distant recurrence. (2) The ML models exhibited better prognostic predictive performance than traditional models. (3) The ML models were superior to traditional models when multiple variables were used. (4) A novel predictive web-based calculator was developed and externally validated to predict survival and site-specific recurrence. Conclusion ML models might be a better analytic approach in CC prognostic prediction than traditional models as they can predict survival and site-specific recurrence simultaneously, especially when using multiple variables. Moreover, our novel web-based calculator may provide clinicians with useful information and help them make individual postoperative follow-up plans and further treatment strategies.

Clear cell renal cell carcinoma (ccRCC) is the most lethal neoplasm of the urologic system. Clinical therapeutic effect varies greatly between individual ccRCC patients, so there is an urgent need to develop prognostic molecular biomarkers to help clinicians identify patients in need of early aggressive management. In this study, samples from primary ccRCC tumor and their corresponding nontumor adjacent tissues (n = 18) were analyzed by quantitative proteomic assay. Proteins downregulated in tumors were studied by GO and KEGG pathways enrichment analyses. Six proteins were found both downregulated and annotated with cell proliferation in ccRCC patients. Of these proteins, PDZK1 and FABP1 were also involved in the lipid metabolism pathway. The downregulation of PDZK1 was further validated in TCGA_KIRC dataset (n = 532) and independent set (n = 202). PDZK1 could discriminate recurrence, metastasis and prognosis between ccRCC patients. Low level of PDZK1 in both mRNA and protein was associated with reduced overall survival (OS) and disease–free survival (DFS) in two independent sets. In univariate and multivariate analyses, PDZK1 was defined as an independent prognostic factor for both OS and DFS. These findings indicated that low level of PDZK1 could predict poor clinical outcome in patients with ccRCC., Highlights • PDZK1, which was involved in cell proliferation and lipid metabolism pathway, was significantly downregulated in ccRCC. • PDZK1 was defined as an independent prognostic factor for OS and DFS in univariate and multivariate cox analyses. • Low level of PDZK1 could predict poor clinical outcome in patients with ccRCC. Clinical therapeutic effect varies greatly between individuals of clear cell renal cell carcinoma (ccRCC). Development of prognostic molecular biomarkers can help clinicians identify patients in need of early aggressive management. Differentially expressed proteins between tumor and adjacent normal tissues were analyzed by proteomics. Subsequently, bioinformatics assay was combined to screen for prognostic markers in ccRCC. PDZ domain containing 1 (PDZK1), involved in cell proliferation and lipid metabolism pathway, was significantly downregulated in ccRCC and defined as an independent prognostic factor for poor clinical outcome in ccRCC patients. Our findings will facilitate patient counseling and individualize management of patients with ccRCC.

Highlights • Colon is a potential site for solitary metastasis from renal cell carcinoma (RCC). • Recurrent disease after curative nephrectomy usually occurs within three years. • Metastatic RCC should be considered in RCC patients with bowel obstruction., Introduction Renal cell carcinoma (RCC) is the most common renal malignancy in adults. Metastatic disease is relatively common at presentation and frequently involves the lung, bone, brain, liver and adrenal glands. After curative resection, there is a 30–40% risk of recurrence, and a 10% risk of developing metastatic disease after 5 years. The gastrointestinal tract, particularly the colon, represents a very uncommon site of late metastatic disease. Presentation of Case We present a case of a 67 year-old-male who underwent a left radical nephrectomy for RCC 9 years before presenting with a metastatic large bowel obstruction. He was later found to have a near-completely obstructing mass in the rectosigmoid colon and underwent a sigmoidectomy with anterior resection of the upper rectum. Histopathology confirmed metastatic RCC confined to the colonic wall with negative microscopic margins. Discussion The tendency of RCC to metastasize to unusual sites such as the pancreas or thyroid gland has been widely reported. However, cases of colon metastasis from RCC are extremely rare. Despite the absence of randomized prospective data, widespread consensus supports the surgical treatment of solitary and oligometastatic disease in light of the poor patient outcomes in non-surgically treated disease (Milovic et al., 2013) [3]. Multiple groups have reported favorable outcomes for surgically resected solitary metastatic disease with long disease-free intervals and good performance status. Conclusion The colon is a potential, though uncommon, site for solitary metastasis from RCC. The clinical presentation is frequently several years after initial curative resection. Oncologic resection with negative margins may result in long-term survival in patients with isolated metastatic disease.

Highlights • Osteosarcoma is the most common primary bone sarcoma. • Neoadjuvant chemotherapy combined with limb salvage surgery (LSS) or amputation are the main strategies in treating limb osteosarcoma. • LSS is associated with a higher 5-year overall survival. • Local recurrence was more frequently encountered in patients treated with LSS, however not affecting overall survival., 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

Next-generation sequencing (NGS) has enabled genome-wide personalized oncology efforts at centers and companies with the specialty expertise and infrastructure required to identify and prioritize actionable variants. Such approaches are not scalable, preventing widespread adoption. Likewise, most targeted NGS approaches fail to assess key relevant genomic alteration classes. To address these challenges, we predefined the catalog of relevant solid tumor somatic genome variants (gain-of-function or loss-of-function mutations, high-level copy number alterations, and gene fusions) through comprehensive bioinformatics analysis of >700,000 samples. To detect these variants, we developed the Oncomine Comprehensive Panel (OCP), an integrative NGS-based assay [compatible with 95% accuracy for KRAS, epidermal growth factor receptor, and BRAF mutation detection as well as for ALK and TMPRSS2:ERG gene fusions. Associating positive variants with potential targeted treatments demonstrated that 6% to 42% of profiled samples (depending on cancer type) harbored alterations beyond routine molecular testing that were associated with approved or guideline-referenced therapies. As a translational research tool, OCP identified adaptive CTNNB1 amplifications/mutations in treated prostate cancers. Through predefining somatic variants in solid tumors and compiling associated potential treatment strategies, OCP represents a simplified, broadly applicable targeted NGS system with the potential to advance precision oncology efforts.

Background There is a paucity of studies reporting long-term survival outcomes for HPV/p16 positive oropharyngeal squamous cell carcinoma (OPSCC). This study aims to compare long-term outcomes of advanced stage p16 positive and negative OPSCCs, treated by surgical and non-surgical modalities. Methods OPSCC patients from 1998 to 2012 were identified through a prospectively collected cancer registry. P16 immunohistochemistry was used as a surrogate marker for HPV-OPSCC. Overall survival (OS) and aspiration free survival (AFS) comparisons were made between patients treated with chemoradiation (CRT) versus primary surgery and radiation/chemoradiation (S+RT/CRT) at 5, 10 and 15 years post-treatment. Results A total of 319 patients were included. P16 positive patients and non-smokers had significantly higher long-term (5, 10 and 15-year) OS. Smokers and p16 negative patients treated with S+RT/CRT had improved long-term OS compared to patients who received CRT. Smokers and p16 negative patients had lower long-term AFS. Multivariate analysis showed improved OS was associated with p16 positivity (HR 0.42, 0.28–0.61) and surgery (HR 0.47, 0.32–0.69), whereas lower OS was associated with ECOG ≥ 2 (HR 2.46, 1.61–3.77), smoking (HR 2.37, 1.41–3.99) and higher stage (HR 1.68, 1.05–2.68). Conclusions In smokers and p16-negative OPSCC patients, primary surgery may be associated with improved long-term survival and dysphagia-related outcomes.

Highlights • Familial multiple lipomatosis (FML) is a rare hereditary benign disease. • The origin of extra-gastrointestinal stromal tumors (EGISTs) remains controversial. • EGISTs and cells of Cajal have similar features—the expression of CD117 and CD34. • Surgical resection is the standard treatment of EGISTs. • Targeted medical therapy of EGISTs by tyrosine kinase inhibitors can be useful., Introduction Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Rarely, GISTs can be located in mesentery, retroperitoneal space, omentum or pancreas. In these cases, the neoplasm is defined as “extra-gastrointestinal stromal tumors” (EGISTs). Presentation of case We reported a case of a 63-year-old male patient diagnosed by computer tomography with large intraabdominal tumor with vague origin, postoperatively determined as an EGIST. The diagnosis was confirmed by immunohistochemical study. The patient had multiple, subcutaneous, painless lipomas localized in the arms, forearms, thighs, abdomen and thorax. Because of the family history and the clinical presentation the disease was determined as familial multiple lipomatosis (FML). We performed radical tumor resection with distal pancreatectomy and splenectomy, and abdominoplasty, removing redundant skin and underlying subcutaneous fat tissue with multiple lipomas. Discussion FML is a rare hereditary benign disease. On the other hand, only few cases with familial GIST have been reported. In cases with extensive abdominal involvement, the primary origin of EGIST may be impossible to determine so the differential diagnosis is very difficult. Conclusion Although we could not prove correlation between the observed diseases, they are extremely rare and their combination is unusual which makes the presented case valuable and interesting.

Solitary fibrous tumors are well described in the pleura, but rare extra-pleural neoplasms have been reported. We describe a patient with a solitary left renal fibrous tumor who after undergoing a nephrectomy, presented 8 years later with a contralateral metachronous solitary fibrous tumor. Malignant metastatic extra-pleural solitary fibrous tumors are extremely rare, and to our knowledge, this is the first case of contralateral recurrence of solitary renal fibrous tumor. The patient underwent a robotic assisted partial nephrectomy of the right renal mass. Both tumors showed overlapping histopathology.

Chronic myeloid leukemia (CML) is the paradigm for targeted cancer therapy. RT-qPCR is the gold standard for monitoring response to tyrosine kinase-inhibitor (TKI) therapy based on the reduction of blood or bone marrow BCR-ABL1. Some patients with CML and very low or undetectable levels of BCR-ABL1 transcripts can stop TKI-therapy without CML recurrence. However, about 60 percent of patients discontinuing TKI-therapy have rapid leukaemia recurrence. This has increased the need for more sensitive and specific techniques to measure residual CML cells. The clinical challenge is to determine when it is safe to stop TKI-therapy. In this review we describe and critically evaluate the current state of CML clinical management, different technologies used to monitor measurable residual disease (MRD) focus on comparingRT-qPCR and new methods entering clinical practice. We discuss advantages and disadvantages of new methods.

Carnitine palmitoyl transferase 1A (CPT1A) protein catalyzes the rate-limiting step of Fatty-acid oxidation (FAO) pathway, which can promote cell proliferation and suppress apoptosis. Targeting CPT1A has shown remarkable anti-leukemia activity. But, its prognostic value remains unclear in Acute Myeloid Leukemia (AML). In two independent cohorts of cytogenetically normal AML (CN-AML) patients, compared to low expression of CPT1A (CPT1Alow), high expression of CPT1A (CPT1Ahigh) was significantly associated with adverse outcomes, which was also shown in European Leukemia Network (ELN) Intermediate-I category. Multivariable analyses adjusting for known factors confirmed CPT1Ahigh as a high risk factor. Significant associations between CPT1Ahigh and adverse outcomes were further validated whether for all AML patients (OS: P = 0.008; EFS: P = 0.002, n = 334, no M3) or for National Comprehensive Cancer Network (NCCN) Intermediate-Risk subgroup (OS: P = 0.021, EFS: P = 0.024, n = 173). Multiple omics analysis revealed aberrant alterations of genomics and epigenetics were significantly associated with CPT1A expression, including up- and down-regulation of oncogenes and tumor suppressor, activation and inhibition of leukemic (AML, CML) and immune activation pathways, hypermethylation enrichments on CpG island and gene promoter regions. Combined with the previously reported anti-leukemia activity of CPT1A's inhibitor, our results proved CPT1A as a potential prognosticator and therapeutic target for AML., Highlights • High expression of CPT1A is an adverse prognostic biomarker in AML. • Aberrant alterations of genomic and epigenomic patterns are significantly associated with CPT1A expression. Identification of prognostic biomarkers is essential for therapeutic choice of AML. This study represents direct evidences that high expression of CPT1A is significantly associated with poor outcomes and abnormal genomic and epigenomic patterns in AML patients. CPT1A is an important catalyzer for fatty-acid oxidation pathway, which may provide alternative carbon source for leukemia proliferation. Findings of this study may indicate the significance of fat metabolism in leukemogenesis.