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Cancer progression is associated with significant cachexia-induced weight loss and stomatitis. Pentoxifylline (PTX) is a drug shown to have beneficial anti-inflammatory effects in cancer patients, mainly through anti-TNFα mechanisms. This study determined the PTX effects and mode of action on weight-loss, stomatitis, and survival in colon cancer patients treated with chemotherapy, examining the kinetics of tumor markers and cytokine levels.Forty patients with metastatic colon cancer receiving chemotherapy, were randomized in this study. Seventeen patients were assigned to the treatment group - 8 received a full PTX dose (400 mg TID) and 9 a reduced dose (200 mg TID). Results were compared to 23 untreated, control patients. Blood analysis of tumor markers (CEA and TPS), inflammatory cytokines (IL-1β, IL-6, IL-8, TNFα, TNF-R), CRP and sIL-2R, were performed. Additionally, clinical parameters were assessed.Patients treated with PTX (full/reduced doses), gained significant weight, and experienced a reduction in stomatitis, resulting in multiple beneficial effects, including improved life quality. Significant reductions in CRP, sIL-2R, and inflammatory cytokine levels, correlated to increases in weight and a reduction in stomatitis. A similar pattern was observed in tumor marker levels, where decreasing levels were correlated with weight gain and reduction in inflammatory cytokine levels.Colon cancer patients receiving PTX with chemotherapy, experienced weight gain and reduced stomatitis occurrence. Beneficial PTX effects were correlated to significant decreases in patient inflammatory cytokines and tumor marker levels, probably due to PTX mode of action.

BackgroundIrradiation, which affects cytokine secretion, is used to treat cancer patients. Cytokine levels have correlations to disease parameters, serving as biomarkers for patients. We aim to explore the effect of irradiation on cytokine production both in vitro (using lymphocytes from healthy donors) and in vivo (using serum levels of head and neck cancer patients following irradiation) and correlating them to mucositis severity/need for percutaneous endoscopic gastroscopy (PEG) tube installation.MethodsCytokine production by cultured lymphocytes from healthy donors, in vitro, following irradiation of 5 or 10 Gy. In addition, blood from 23 patients with head and neck cancers, irradiated by 60–72G in vivo, were assessed for inflammatory cytokines (tumor necrosis factor (TNF)α, interleukin (IL)-6, IL-8, IL-18), the anti-inflammatory cytokine IL-10, and the general marker sIL-2R. Following radiation, selected patients who were developing mucositis were treated by PEG tube installation. Changes in cytokine levels were studied as predictive biomarkers of response to therapy/PEG tube installation. Cytokine production levels were measured using ELISAs kits.ResultsIrradiation decreased the levels of all tested cytokines, most notably IL-6 and IL-8, proportional to irradiation dose. In patients, increases in cytokine levels, correlated with mucositis severity and potentially the need for PEG tube installation.ConclusionsIrradiation decreased the levels of all cytokines of healthy lymphocytes in a dose-dependent manner, especially those of IL-6 and IL-8. This study shows a correlation between high and increasing levels of inflammatory cytokines, sIL-2R, plus radiation toxicity and the need for PEG. The reduction of cytokine levels after radiotherapy predicts that PEG will not be required. Thus, our study shows that cytokine changes are predictive biomarkers in head and neck cancer patients.

Purpose: Heparanase is the predominant enzyme that cleaves heparan sulfate, the main polysaccharide in the extracellular matrix. Whereas the role of heparanase in sustaining the pathology of human cancer is well documented, its association with prostate carcinoma remains uncertain. Our research was undertaken to elucidate the significance of heparanase in prostate tumorigenesis and bone metastasis.Experimental Design: We applied immunohistochemical analysis of tissue microarray, in vitro adhesion and invasion assays, as well as mouse models of intraosseous growth and spontaneous metastasis of prostate cancer, monitored by whole-body bioluminescent imaging. Electroporation-assisted administration of anti-heparanase small interfering RNA in vivo was applied as a therapeutic approach.Results: We report a highly statistically significant (P < 0.0001) prevalence of heparanase overexpression in prostate carcinomas versus noncancerous tissue, as well as strong correlation between tumor grade and the extent of heparanase expression. We observed >5-fold increase in the metastatic potential of PC-3 prostate carcinoma cells engineered to overexpress heparanase. Notably, overexpression of a secreted form of the enzyme also led to a dramatic increase in intraosseous prostate tumor growth. Local in vivo silencing of heparanase resulted in a 4-fold inhibition of prostate tumor growth, representing the first successful application of anticancer therapy based on heparanase small interfering RNA and validating the potential of heparanase as a target for prostate cancer treatment.Conclusions: Heparanase directly contributes to prostate tumor growth in bone and its ability to metastasize to distant organs. Thus, anti-heparanase strategy may become an important modality in the treatment of prostate cancer patients, particularly those with bone metastases.

Supplementary Figure S1 from Function of Heparanase in Prostate Tumorigenesis: Potential for Therapy

Supplementary Figures 1-2 from Role of Heparanase in Radiation-Enhanced Invasiveness of Pancreatic Carcinoma

Therapeutic strategies for advanced head and neck squamous carcinoma (HNSCC) consist of multimodal treatment, including Epidermal Growth Factor Receptor (EGFR) inhibition, immune-checkpoint inhibition, and radio (chemo) therapy. Although over 90% of HNSCC tumors overexpress EGFR, attempts to replace cytotoxic treatments with anti-EGFR agents have failed due to alternative signaling pathways and inter-tumor heterogeneity.

BACKGROUND: Cancer progression is associated with significant systemic clinical manifestations including cachexia induced weight loss and anorexia. Pentoxifylline (PTX) is a drug that has been shown to have multiple beneficial effects in cancer patients through its anti-inflammatory properties. MAIN OBJECTIVE: To evaluate PTX effects on colon cancer patients treated with chemotherapy. PATIENTS and METHODS: Forty metastatic colon cancer patients receiving chemotherapy were enrolled in this randomized study. 17 patients were treated with a full dose of PTX (400 mg TID), 9 patients with a reduced dose PTX (200 mg TID) and 23 served as controls (no PTX). RESULTS: Follow-up evaluations of patients included the following: physical examination; leukopenia determination; weight determination; stomatitis determination; and survival rate. Patients treated with PTX (both full and reduced doses), experienced a significant increase in weight and a reduction in stomatitis relative to the control group. Treatment with PTX also significantly increased patient survival rate. All patients treated with PTX, had a median overall survival (OS) rate of 20.4 months as compared to 13.2 months in the control group. CONCLUSIONS: PTX treatment of colon cancer patients, in addition to chemotherapy, significantly improved survival rates, induced weight gain and reduced stomatitis occurrence –all important parameters of cachexia.

To assess the efficacy and safety of 177Lu-DOTATATE in patients with somatostatin receptor (SSR) positive lung neuroendocrine tumor (NET). Methods: This is a retrospective review of the outcome of patients with typical carcinoid (TC) and atypical carcinoid (AC), treated with 177Lu-DOTATATE at two ENETS Centres of Excellence. Morphological imaging (RECIST 1.1) and 68Ga-DOTATATE PET/CT responses were assessed at 3 months after completion of 177Lu-DOTATATE. Concordance between two response assessment methods was evaluated by Kappa statistics. Progression-free survival (PFS) and overall survival (OS) was estimated by Kaplan-Meier analysis and compared by Log-rank test. Treatment-related adverse events (AEs) were graded based on CTCAE version 5. Results: Of 48 patients (median age, 63 years, 13 female), 43 (90%) had AC and 5 (10%) TC. Almost all patients (47, 98%) were treated due to progression. Majority (40, 83%) received somatostatin analogs and 10 patients (20%) had prior everolimus, chemotherapy or both. All patients had high SSR expression (≥ modified Krenning score 3) on pre-treatment 68Ga-DOTATATE PET/CT. Patients received a median 4 (range 1-4) cycles of 177Lu-DOTATATE (33% with concurrent radiosensitizing chemotherapy) to a median cumulative activity of 27GBq (range 6-43GBq). At median follow-up of 42 months, the median PFS and OS were 23 months (95% CI 18-28 months) and 59 months (95% CI 50-not reached [NR]), respectively. Of 40 patients with RECIST-measurable disease and 39 patients with available 68Ga-DOTATATE PET/CT response categories were: partial response, 20% (95% CI 10-35%) and 44% (95% CI 30-59%); stable disease, 68% (95% CI 52-80%) and 44% (95% CI 30-59%) and progressive disease 12% (95% CI 5-27%) by both, respectively. There was a moderate concordance between response categories by RECIST and 68Ga-DOTATATE PET/CT, weighted Kappa of 0.51 (95% CI 0.21-0.68). Of patients with stable disease by RECIST, those with partial response on 68Ga-DOTATATE PET/CT had longer OS compared to those with no response, NR vs 52 months (95% CI 28-64), HR 0.2 (95% CI 0.1-0.6), p 0.001. Most grade 3/4 AEs were reversible and the most common was lymphopenia (14%) with no incidence of myelodysplasia/leukemia. Conclusion: In patients with advanced progressive lung NET and satisfactory SSR expression, 177Lu-DOTATATE is effective and safe with a high disease control rate and encouraging PFS and OS.

Gabriel Molineros, Amichay Meirovitz, Marc Wygoda, Mohammad Zuaiter, Vladimir Yutkin, Mordechai Duvdevani, Guy Hidas, Ofer N Gofrit Department of Urology, Hadassah Hebrew University Hospital, Jerusalem, IsraelCorrespondence: Ofer N GofritDepartment of Urology, Hadassah Hebrew University Hospital, P.O. Box 12000, Jerusalem, 91120, IsraelTel +972 2-6776874Fax +972 2-6430929Email ogofrit@gmail.comPurpose: Patients treated by external beam radiotherapy (EBRT) for localized carcinoma of the prostate (CAP) often suffer from urinary obstruction. While most patients can be treated medically, some require transurethral prostatectomy (TURP) for alleviation of obstruction. The consequences of combing EBRT and TURP are controversial. The objective of this study was to evaluate the success and complication rates of TURP combined with EBRT.Patients and Methods: Between 2001 and 2017, 3501 patients underwent TURP. Sixty-six of them were treated with EBRT for CAP. Surgical complications according to the Clavien–Dindo (CD) scale and the need for secondary interventions were compared to 66 randomly selected patients operated on for benign prostatic hyperplasia (BPH).Results: Patients who underwent TURP for BPH were significantly older compared to the patients with CAP with an average of 76.4 (SD 4.3) vs 71 (SD 8.2) years, p< 0.0001. Substantial post-operative complications were rare in both groups with only a single case of CD grade 3 in each group. However, patients with CAP required significantly more secondary surgeries (21% vs 6%, p=0.02) and significantly more additional interventions (37.9% vs 13.6%, p=0.0025). There was no difference in complication rate, in the need for additional interventions or in the oncological outcome when comparing patients operated before or after EBRT.Conclusion: The complication rate of TURP done before or after EBRT is low and comparable to surgery for BPH. However, the rates of secondary surgeries and additional interventions in these patients are high (40%). TURP before or after EBRT provides similar results.Keywords: carcinoma of the prostate, external beam radiotherapy, transurethral prostatectomy

Background Osteoradionecrosis (ORN) of the jaw is currently defined by the development of osteonecrosis in head/neck irradiated patients, regardless of lesion exposure. To diagnose medication-related osteonecrosis of the jaw (MRONJ), a history of any radiation therapy to the jaw region must be ruled out. The aim of this study was to assess the accuracy of current osteonecrosis criteria, while introducing new modifications for improved diagnosis and treatment. Methods One hundred and forty-one necrotic lesions were analyzed from patients exposed to bone-modifying agents (BMAs) and/or received head and neck regional radiation therapy, where the maximal dose of radiation exposure to the jaw osteonecrosis site was calculated. Modified diagnostic criteria were used to reassess all cases and a comparison of outcomes was performed using Pearson’s Chi-Square/Fisher’s exact test. Results Only in patients with primary head and neck carcinomas did the maximal mean radiation dose in the necrotic jaw site reach ranges associated with ORN formation (>40 Gy), with individual cases showing exposures as low as 0–2 Gy. Based on the modified diagnostic criteria almost 2/3 of the necrotic cases diagnosed as ORN should be diagnosed as MRONJ. Conclusions ORN diagnosis should only be considered in cases of radiation exposure >40 Gy to prevent misdiagnosis and suboptimal treatment. A modified criterion for MRONJ diagnosis is recommended where radiation exposure 40 Gy and BMA administration, an additional modification to diagnostic criteria of ‘medication- and radiation-related osteonecrosis of the jaw’, should be used.

Treatment regimens for patients with metastatic or recurrent post-radiation, locoregional, unresectable salivary cancer are limited. An inverse correlation between somatostatin receptor 2 (SSTR2) and the proliferating marker Ki-67 in neuroendocrine tumors has enabled a treatment plan for metastatic disease, utilizing peptide receptor radionuclide therapy. Interestingly, healthy salivary glands express high levels of SSTR2. In this study, the presence of SSTR2, its correlation with Ki-67 in glandular salivary carcinomas and the clinical applicability thereof was determined. In the retrospective part of this study, 76 adequate tumor tissue specimens obtained from patients diagnosed with primary or metastatic salivary carcinomas between 1988 and 2016, were collected for tissue array and histologically classified. Immunohistochemistry was performed to determine the presence, relative expression and potential correlation of SSTR2 and Ki-67. The clinical significance of SSTR2 expression was determined by prospectively assessing 68Ga-DOTATATE uptake using PET-CT imaging, in patients diagnosed with metastatic salivary gland malignant tumors between 2015 and 2016. Sixty-three primary cancer tumors and 14 metastatic tumors were tested. All tumor subtypes were found to express SSTR2 to some extent. The highest expression was seen in Mucoepidermoid carcinoma (MEC) tissues where the majority of specimens (86.4%) expressed SSTR2. A relatively strong immunohistochemical staining score for SSTR2 was observed in MEC, adenoid cystic carcinoma and polymorphous adenocarcinoma. Interestingly, an inverse correlation between SSTR2 and Ki-67 expressions was observed (44%) in MEC tissue. Uptake of 68Ga-DOTATATE was visualized using PET-CT imaging in 40% of patients, across metastatic MEC and ACC. All observations were found to be statistically significant. This study confirms the expression of SSTR2 in glandular salivary carcinomas and an inverse correlation in expression levels between SSTR2 and Ki-67. This lays a foundation for novel treatment options in salivary metastatic cancers where SSTR2 may be a potential novel therapeutic target.

Background/aim Thyroid hormones (THs) stimulate breast cancer (BC) cell proliferation. We hypothesized that these hormones and the proliferative marker thymidine kinase 1 (TK1) represent the initial and final steps of the proliferative pathway, respectively. Patients and methods We measured the serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), along with serum TK1 activity, in 144 newly diagnosed BC patients, and examined the associations between THs and proliferation in different BC receptor profiles. Results TK1 activity did not correlate with TSH (r=0.06, p=0.473) or FT4 levels (r=0.04, p=0.665), but did correlate with FT3 levels (r=0.28, p=0.001). Elevated FT3 (>6.0 pmol/l) predicted increased TK1 activity (>140 Du/l) after adjusting for age (odds ratio 4.1, p=0.014). We also found a significant association of the combined elevation of FT3 and TK1, assumed as a surrogate marker of accomplished proliferative signal, with triple-negative (TN) profile (p=0.003). The rates of combined FT3 and TK1 elevation in TN and ER-positive profiles were 20.0% and 1.8%, respectively (p=0.005). Conclusion FT3 may be involved in proliferative signaling, as measured by TK1 activity, predominately in TN breast cancer.

The reported results of trimodal treatment (TMT) in muscle‐invasive bladder cancer vary widely. We attempted to characterize the profile of ideal candidates for this approach. Between 2000 and 2019, 105 patients (median age 78 years) with T2‐4aN0M0 bladder cancer were treated with TMT and analyzed retrospectively. Mean radiotherapy dose was 62 Gy (SD 8.4). Ten pretreatment prognostic parameters were evaluated including tumor diameter on pre‐TURBT CT. Multivariate analyses was performed and combination of parameters was studied. After a median follow‐up of 29 months, 53 patients (50.5%) developed recurrence and 70 patients (67.7%) died. Death was disease‐specific in 46 patients (65.7%). Tumor diameter was the most significant prognostic parameter with p 5 cm TMT renders unacceptably poor treatment outcomes., Bladder tumor diameter on pretreatment CT is the single best predictor of tumor volume and of response to trimodal therapy. In cisplatin‐eligible patients with a tumor diameter ≤3 cm, trimodal treatment provides 5‐year disease‐specific survival of 80%

Context Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis for both locally advanced and metastatic disease. Standard treatment with combination etoposide–doxorubicin–cisplatin–mitotane (EDP-M) is highly toxic and some patients benefit from mitotane monotherapy. However, identification of these patients remains challenging. Objective We present a summary of the Israeli national referral center’s 20 years of experience in treating advanced ACC, with the aim of identifying prognostic factors and assisting in treatment decision making. Methods We conducted a retrospective multivariate analysis of patients treated for metastatic or locally advanced ACC at Hadassah Medical Center between 2000 and 2020 to determine clinical, pathological, and treatment factors correlated with overall survival (OS). Results In our cohort of 37 patients, a combination of modified European Network for the study of Adrenal Tumors (mENSAT) staging with either grade and R status, or age and symptoms was validated to stratify prognosis (P = .01 and P = .03, respectively). Patients who underwent R0 resection followed by radiotherapy or metastasectomy for oligometastatic disease had longer OS than patients with residual disease: median OS of 55 months vs 14 months, respectively, hazard ratio 3.1 (CI 1.4-6.7, P = .005). Patients treated with mitotane monotherapy had a significantly better prognosis, yet this result was attenuated in a multivariate analysis controlling for mENSAT and R status. Of patients treated with EDP-M, 41.4% experienced grade 3 or higher adverse events. Conclusion Patients with advanced ACC achieving R0 status have a better prognosis and might benefit from mitotane monotherapy.

Many experimental studies have suggested the importance of thyroid hormones in breast cancer (BC) morphogenesis. The aim of this study was to evaluate the association of thyroid hormone levels in serum of patients with primary BC with morphological presentations of the disease in pathological specimens and prognosis.We measured the serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), along with serum thymidine kinase 1 activity and examined their relation to pathological features and prognosis of 158 patients with primary BC.We found a significant positive association of serum FT3 level with the presence of carcinoma in situ component (CIS) (p=0.032) and its size (p=0.047), with the presence (p=0.022) and the number of multifocal/multicentric tumors (MMTs) (p=0.002), as well as with increased proliferative activity in terms of serum thymidine kinase 1 (p=0.002). Moreover, we report that each 1.0 unit rise of FT3/FT4 ratio×10 was associated with an odds ratio of 1.77 (95% confidence interval=1.17-3.30, p=0.007), 1.97 (95% confidence interval=1.17-2.67, p=0.010) and 1.56 (95% confidence interval=1.02-2.37, p=0.039) for the detection of patients with CIS, MMTs and lymphovascular invasion, respectively, after adjusting for age. We did not find statistically significant associations of serum TSH level with breast cancer`s parameters. A Cox regression survival analysis identified serum FT3 level5.95 pmol/l as a risk factor for BC recurrence (relative risk=2.65, p=0.017), a finding that retained significance in a multivariate model (relative risk=2.52, p=0.027).The FT3/FT4 ratio is a valuable parameter predicting the presence of CIS, MMTs and lymphovascular invasion in pathological specimens. An elevated serum FT3 level is associated with the presence of CIS, MMTs, increased proliferative activity and poor prognosis.

The aim of this study was to evaluate the predictive power of the absorbed dose to kidneys after the first course of treatment with [177Lu]-DOTA-TATE on the cumulative kidney absorbed dose after 3 or 4 cycles of treatment.Peptide receptor radionuclide therapy (PRRT) with [177Lu]-DOTA-TATE is an effective treatment for somatostatin receptor positive neuroendocrine tumors (NETs). Post-treatment scans (PTS) are required after each cycle of treatment for personalized radiation dosimetry in order to calculate the dose to organs and tumors and to ensure a cumulative absorbed dose to kidneys under a safety threshold of 25 Gy.A total of 187 patients who completed treatment and underwent PTS for dosimetry calculation were included in this retrospective study. The correlation between the cumulative absorbed dose to the kidneys after completion of treatment and the absorbed dose after the first cycle(s) was studied. Multilinear regression analysis was performed to predict the cumulative absorbed dose by the kidneys in the subsequent cycles. An algorithm for the follow-up of the kidney absorbed dose is proposed.When the absorbed dose to kidneys after the first cycle of treatment is below 5.6 Gy, four cycles of treatment can be safely administered with a cumulative dose less than 25 Gy (p 0.1). For the remaining patients, the cumulative dose absorbed after 3 or 4 cycles of treatment can be predicted after the second cycle of treatment. This protocol enabled early decisions on the number of treatment cycles and reduced the number of post-treatment SPECT/CT studies for dosimetry in 34% of patients, as well as hospitalization time for 56% of the treatment cycles.Assessment of the kidney absorbed dose after PRRT can be simplified with the algorithm presented in this study. This approach enabled early decisions on the number of therapy cycles in 75% of patients.The validity of these results is limited to the protocol of dosimetry calculation used in our institution. Implementation in other centers may require standardization of the acquisition parameters and the dosimetry protocol.

Background The standard chemotherapy treatment protocol for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) requires as long as 56 days of hospitalization over six months. Where the 5-Fluorouracil (5-FU) pump is available, most treatment will be on outpatient bases, however patients will still be under chemotherapy treatment for a comparable period of time (around 50 days). Aim A modified protocol was assessed to decrease hospitalization and/or chemotherapy treatment time without sacrificing outcomes, to potentially increase patient quality of life. Methods and results A retrospective analysis (2005-2018) of recurrent/metastatic HNSCC patients with a modified treatment protocol was performed. Treatment consisted of cisplatin, cetuximab, 5-fluorouracil bolus and leucovorin administered on day 1 of a 2-week cycle, and a continuous infusion of 5-fluorouracil on days 1-2 of the cycle. Outcomes were measured by progression-free survival, overall survival, and patient hospitalization time. Analysis was done using the Kaplan-Meier survival function curve. The study cohort consisted of 27 patients. The modified treatment protocol resulted in a median progression-free survival of nine months and median overall survival of 14 months, while hospitalization time was reduced by almost 80% in the first six months of treatment. Conclusions Modification of the cisplatin, cetuximab, 5-FU and leucovorin protocol to a bi-weekly regimen utilizing alternative drug delivery methods, significantly reduced patient hospitalization from 56 days to 12 days in the first 6 months of treatment. This was achieved without compromising treatment outcome, while significantly reducing the days patients were exposed to chemotherapy, and thus potentially improving quality of life.

Authors' Response to the Letter by Lamarca et al. Entitled "Temozolomide-Capecitabine Chemotherapy for Neuroendocrine Neoplasms : The Dilemma of Treatment Duration" Regarding "Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms"

Objectives To evaluate the utility of different Apparent Diffusion Coefficient (ADC) values on Diffused Weighted Magnetic Resonance Imaging (DW-MRI) for nasopharyngeal carcinoma (NPC). Study design and setting A retrospective cohort study in a single tertiary medical center. Subjects and methods The study group consists of patients with pathology proven NPC that underwent DW-MRI prior or/and following a non-surgical chemo radiation treatment between the years 2007 and 2017. ADC thresholds were analyzed and compared for primary (pre-treatment) and expected post-irradiation NPC cases and healthy controls. Results We recruited 144 patients who underwent 195 MRI's for NPC. 25 DW-MRI were performed before (primary, active NPC) and 56 following (no residual NPC) treatment. 45 out of 225 patients who had brain DW-MRI for other reasons (control group) had measurable nasopharynx tissue (N = 33, adjusted for age and gender). The mean ADC of NPC prior to treatment (0.69 ± 0.13 × 10−3 mm2/s) was significantly lower (ANOVA, P Conclusions ADC levels have distinct values in newly diagnosed and follow up of NPC.

Purpose Primary sarcoma of the heart is a rare but devastating tumor. Median survival with conventional treatment is 8-12 months. When resection is not feasible, patients often succumb to heart failure secondary to obstruction of blood flow, valve dysfunction, chamber compression or conduction abnormalities. Palliative treatment options include systemic chemotherapy and external beam irradiation. We herein describe a novel technique using endovascular brachytherapy, aiming at reducing tumor mass, alleviating right ventricular pressure overload and at the same time keeping the option of R0 resection viable. Material and methods A 35-year-old man was diagnosed with a non-resectable high-grade intimal sarcoma of the right ventricle (RV), main pulmonary artery (PA) and right PA. After three cycles of doxorubicin and ifosfamide, the patient's symptoms of right heart failure worsened. Imaging documented tumor progression and supra-systemic pulmonary artery pressure. Through a trans-femoral venous access, a brachytherapy sleeve was placed in the RV and main and right PA. A dose of 20 Gy was delivered over a period of ten minutes. Results The patient had an uneventful course and was discharged home 24 hours after the procedure. Ten months after brachytherapy, repeat imaging demonstrated a significant reduction in tumor volume and an increase in pulmonary artery cross-sectional area with a marked reduction of pulmonary artery pressure, leading to a complete resolution of heart failure symptoms. Conclusions Endovascular brachytherapy is a novel, safe and effective therapeutic modality for non-resectable primary cardiac sarcomas either for palliation of obstruction, or tumor mass reduction to allow complete resection.

Rectal neuroendocrine neoplasia (NEN) is more common than other NEN origins, but is less commonly metastatic. However, when present, distant disease carries a particularly poor prognosis. Evidence guiding optimal treatment of such patients is lacking. We assessed PRRT outcomes in patients with somatostatin receptor (SSTR) positive metastatic rectal NEN from two referral centres. Patients treated with PRRT were retrospectively reviewed. Morphologic (RECIST 1.1), SSTR imaging responses and toxicity were assessed 3 months post-PRRT. Kaplan-Meier estimate was used to determine progression-free survival (PFS) and overall survival (OS) from start of PRRT. Twenty-seven consecutive patients (M = 20, age 31-81 years) were reviewed. The majority (70%) had ENETs grade 2 disease (19 patients), three had Grade 3, one Grade 1, and four not documented. Overall, 63% (10/16 patients with available FDG PET/CT) had FDG avid disease. Twenty-six patients were treated for disease progression. Most had 177Lu-DOTA-octreotate with median cumulative activity of 30 GBq, median four cycles. 14 patients had radiosensitising chemotherapy (5FU or capecitabine). At 3 months post-PRRT, CT disease control rate (DCR) was 96%: partial response was observed in 70% (19/27) and stable disease in 26%. All but one had partial SSTR imaging response. The median PFS was 29 months. Ten patients died, with median overall survival 81 months with a median follow-up of 67 months. Seventeen patients had further treatments after initial PRRT (10 had further cycles of PRRT). Three patients had grade 3 lymphopenia, without significant renal toxicity, MDS or leukaemia. Our results indicate high efficacy and morphologic responses with minimal toxicity and very encouraging survival from PRRT in patients with metastatic rectal NEN despite the adverse prognostic features of this cohort. Further prospective PRRT trials are warranted in this subgroup.

SummaryTriple negative breast cancer (TNBC) is an aggressive type of cancer that is known to be resistant to radiotherapy (RT). Evidence is accumulating that is indicative of the plasticity of TNBC, where one cancer subtype switches to another in response to various treatments, including RT. In this study we aim to overcome tumor resistance by designing TNBC-sensitizing targeted therapies that exploit the plasticity occurring due to radiation exposure. Using single cell analysis of molecular changes occurring in irradiated TNBC tumors, we identified two initially undetected distinct subpopulations, represented by overexpressed Her2 and cMet, expanding post-RT and persisting in surviving tumors. Using murine cancer models and patient-derived TNBC tumors, we showed that only simultaneous targeting of Her2 and cMet was successful in sensitizing TNBC to RT and preventing its regrowth. The strategy presented herein holds the potential to be broadly applicable in clinical use.HighlightsSensitization of TNBC to radiotherapy (RT) is a clinically unmet needSingle cell strategy creates a precise map of subpopulations expanding post-RTEvolution of intra-tumor heterogeneity is turned into a therapeutic advantageSimultaneous targeting of expanding subpopulations sensitizes TNBC to radiotherapy

Background/aim Prognostic factors serve as a vital tool in the treatment of patients with head and neck cancer (HNC). The aim of this study was to evaluate the clinical potential of Thymidine-kinase-1 (TK1) marker in the prognosis of HNC patients. Patients and methods We evaluated 366 blood samples from 278 HNC patients and 88 healthy controls, using an ELISA assay. Correlations of TK1 levels with disease stage, lymph node involvement and response to radiation therapy, were determined. Results In HNC patients, TK1 levels were significantly higher compared to healthy controls. Significantly higher TK1 levels were demonstrated in node positive cases and in advanced disease stages compared to node negative and early disease stages. Levels were higher prior to radiation and decreased significantly thereafter, in patients responding to treatment. Increasing levels of TK1 post-radiation were indicative of recurrence or of non-response to treatment, while decreasing levels indicated a positive response. Conclusion TK1 is a tumor marker in HNC patients with the ability to assess response to therapy. High or increasing levels correlated to a poor prognosis, whereas low levels correlated to an overall increased survival.