Clinical effectiveness of combined whole body hyperthermia and external beam radiation therapy (EBRT) versus EBRT alone in patients with painful bony metastases: A phase III clinical trial study.

PURPOSE: To evaluate the response rate, pain relief duration, and time it took for pain to decline or resolve after radiation therapy (RT) with or without fever-range Whole Body Hyperthermia (WBH) in bony metastatic patients with mainly primary tumor of prostate and breast cancer leading to bone pain. MATERIALS & METHODS: Bony metastatic patients with pain score ≥4 on the Brief Pain Inventory (BPI) underwent RT of 30 Gy in 10 fractions in combination with WBH with nursing care under medical supervision versus RT-alone. WBH application time was 3-4 h in three fractions with at least 48-h intervals. All patients were stratified primary site, breast or prostate cancer vs others, BPI score, and exclusion criteria. The primary endpoint was complete response (CR) (BPI equal to zero with no increase of analgesics) within two months of follow-up. RESULTS: Based on this study, the RT-alone group showed the worst pain. The study was terminated after the enrollment of a total of 61 patients, 5 years after the first enrollment (April 2016 to February 2021). Finally, the CR rate in RT + WBH revealed the most significant difference with RT-alone, 47.4% versus 5.3% respectively within 2 months post-treatment (P-value <0.05). The time of complete pain relief was 10 days for RT + WBH, while the endpoint was not reached during the RT-alone arm. Pain progression or stable disease was observed in half of the patients in RT-alone group within 4 weeks after treatment. However, this score was near zero in RT + WBHT patients in two months post-treatment. CONCLUSIONS: WBH plus RT showed significant increases in pain relief and shorter response time in comparison with RT-alone for patients with bone metastatic lesions.

Intra-prostatic gold fiducial marker insertion for image-guided radiotherapy (IGRT): five-year experience on 795 patients.

INTRODUCTION: Prostate cancer is the second most commonly diagnosed cancer in males. The use of intra-prostatic fiducial markers (FM) for image-guided radiotherapy (IGRT) has become widespread due to their accuracy, relatively safe use, low cost, and reproducibility. FM provides a tool to monitor prostate position and volume changes. Many studies reported low to moderate rates of complications following FM implantation. In the current study, we present our five years' experience regarding the insertion technique, technical success, and rates of complication and migration of intraprostatic insertion of FM gold marker. METHODS: From January 2018 to January 2023, 795 patients with prostate cancer candidate for IGRT (with or without a history of radical prostatectomy) enrolled in this study. We used three fiducial markers (3*0.6 mm) inserted through an 18-gauge Chiba needle under transrectal ultrasonography (TRUS) guidance. The patients were observed for complications up to seven days after the procedure. Besides, the rate of marker migration was recorded. RESULTS: All procedures were completed successfully, and all patients tolerated the procedure well with minimal discomfort. The rate of sepsis after the procedure was 1%, and transient urinary obstruction was 1.6%. Only two patients experienced marker migration shortly after insertion, and no fiducial migration was reported throughout radiotherapy. No other major complication was recorded. DISCUSSION: TRUS-guided intraprostatic FM implantation is technically feasible, safe, and well-tolerated in most patients. The FM migration can seldom occur, with negligible effects. This study can provide convincing evidence that TRUS-guided intra-prostatic FM insertion is an appropriate choice for IGRT.

Predicting breast cancer response to neoadjuvant chemotherapy using ensemble deep transfer learning based on CT images.

OBJECTIVE: To develop an ensemble a deep transfer learning model of CT images for predicting pathologic complete response (pCR) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). METHODS: The data were obtained from the public dataset 'QIN-Breast' from The Cancer Imaging Archive (TCIA). CT images were gathered before and after the first cycle of NAC. CT images of 121 breast cancer patients were used to train and test the model. Among these patients, 58 achieved a pCR and 63 showed a non-pCR based pathology examination of surgical results after NAC. The dataset was split into training and testing subsets with a ratio of 7:3. In addition, the number of training samples in the dataset was increased from 656 to 1,968 by performing an image augmentation method. Two deep transfer learning models namely, DenseNet201 and ResNet152V2, and the ensemble model with a concatenation of two models, were trained and tested using CT images. RESULTS: The ensemble model obtained the highest accuracy of 100% on the testing dataset. Furthermore, we received the best performance of 100% in recall, precision and f1-score value for the ensemble model. This supports the fact that the ensemble model results in better-generalized model and leads to efficient framework. Although a 0.004 and 0.003 difference were seen between the AUC of two base models (DenseNet201 and ResNet152V2) and the proposed ensemble, this increase in the model quality is critical in medical research. T-SNE revealed that in the proposed ensemble, no points were clustered into the wrong class. These results expose the strong performance of the proposed ensemble. CONCLUSION: The study concluded that the ensemble model can increase the ability to predict breast cancer response to first-cycle NAC than two DenseNet201 and ResNet152V2 models.

Predictors of chemotherapy-induced severe anemia in cancer patients receiving chemotherapy.

PURPOSE: Chemotherapy-induced anemia is a frequent complication of systemic chemotherapy and is associated with decreased functional capacity and quality of life. The objective of this study was to identify the candidate variables most likely to be associated with chemotherapy-induced severe anemia (hemoglobin < 8 g/dL) in patients treated with cytotoxic chemotherapy. METHODS: A total of 14 clinical and laboratory covariates were prospectively evaluated at baseline in a cohort of consecutive cancer patients receiving cytotoxic chemotherapy. The anemia risk category for each chemotherapy regimen used was determined based on pivotal trials published in the literature. All regimens were classified to three categories (high risk, intermediate risk, and low risk). Logistic regression analysis adjusted for the regimen risk was used to determine the candidate risk factors associated with chemotherapy-induced anemia. RESULTS: A total of 305 patients were included in the study. Administration of high-risk regimens (i.e., regimens with ≥ 20% risk of anemia in a pivotal trial) was demonstrated to be a novel independent predictive factor for severe anemia (odds ratio 3.33, p = 0.005). Considering regimen risk as an adjustment factor, 5 readily available predictors including low hemoglobin, body mass index (BMI) less than 23 kg/m2, low hematocrit, high haptoglobin, and high ferritin were associated with the outcome. CONCLUSIONS: The application of these candidate predictors would be helpful in classifying patients at risk for severe anemia, who might be appropriate candidates for prophylactic erythropoietin. Multivariable models including such promising candidate predictors need to be developed.

Predicting chemotherapy-induced thrombocytopenia in cancer patients with solid tumors or lymphoma.

PURPOSE: Chemotherapy-induced thrombocytopenia is a serious complication in chemotherapy-treated patients. Identification of patients at risk for chemotherapy-induced thrombocytopenia could have clinical value in personalized management of patients and optimized administration of prophylactic thrombopoietic agents. The aim of this study was to develop a predictive model for chemotherapy-induced thrombocytopenia (platelet count < 100,000/µl) in cancer patients undergoing chemotherapy. METHODS: A total of 14 covariates were prospectively assessed as explanatory variables in a cohort of consecutive patients with solid tumors or lymphoma. A multivariable logistic regression model was developed after univariable analysis. A bootstrapping technique was applied for internal validation. RESULTS: Data from 305 patients during 1732 chemotherapy cycles were considered for analysis. Forty-eight patients (15.73%) developed chemotherapy-induced thrombocytopenia during their treatment course. The multivariable model exhibited three final predictors for chemotherapy-induced thrombocytopenia, including high ferritin (odds ratio, 4.41; bootstrap P = 0.001), estimated glomerular filtration rate <60 ml/min/1.73 m2 (odds ratio, 3.08; bootstrap P = 0.005), and body mass index <23 kg/m2 (odds ratio, 2.23; bootstrap P = 0.044). The main characteristics of the model include sensitivity 75%, specificity 65.4%, positive likelihood ratio 2.16, and negative likelihood ratio 0.382. Moreover, the model was well calibrated (Hosmer-Lemeshow P = 0.713) and the area under the receiver operating characteristic curve was 0.735 (95% confidence interval, 0.654-0.816; P < 0.001). CONCLUSIONS: We developed a predictive model for chemotherapy-induced thrombocytopenia based on readily available and easily assessable clinical and laboratory factors. This study may provide a valuable insight to guide optimized treatment of cancer patients. Further studies with larger sample size are warranted.

Analysis of trace elements in human hair through X-ray fluorescence spectroscopy for screening of prostate cancer.

Background: Use of hair samples to analyze the trace element concentrations is one of the interesting fields among many researchers. X-ray fluorescence (XRF) is considered as one of the most common methods in studying the concentration of elements in tissues and also crystalline materials, using low energy X-ray. In the present study, we aimed to evaluate the concentration of the trace elements in the scalp hair sample through XRF spectroscopy using signal processing techniques as a screening tool for prostate cancer. Methods: Hair samples of 22 men (including 11 healthy and 11 patients) were analyzed. All the sample donors were Iranian men. EDXRF method was used for the measurements. Signals were analyzed, and signal features such as mean, root-mean-square (RMS), variance, and standard deviation, skewness, and energy were investigated. The Man-Whitney U test was used to compare the trace element concentrations. The analysis of variance (ANOVA) test was used to identify which extracted feature could help to identify healthy and patient people. P values ≤ 0.05 were considered statistically significant. Statistical analysis was performed using SPSS 16.0 software. Results: The mean±SD age was 67.8±8.7 years in the patient group and 61.4±6.9 years in the healthy group. There were statistically significant differences in the aluminum (Al, P<0.001), silicon (Si, P=0.006), and phosphorus (P, P=0.028) levels between healthy and patient groups. Skewness and variance were found to be relevant in identifying people with cancer, as signal features. Conclusion: The use of EDXRF is a feasible method to study the concentration of elements in the hair sample, and this technique may be effective in prostate cancer screening. Further study with a large sample size will be required to elucidate the efficacy of the present method in prostate cancer screening.

Rectal retractor application during image-guided dose-escalated prostate radiotherapy.

PURPOSE: To investigate efficacy of a rectal retractor (RR) on rectal dose during image-guided dose-escalated prostate three-dimensional conformal radiotherapy (3DCRT). PATIENTS AND METHODS: In all, 21 patients with localized prostate cancer were treated with a RR for 3DCRT in 40â€¯× 2 Gy. Patient underwent two scans for radiotherapy planning, without and with RR. RR was used for the first half of the treatment sessions. Two plans were created for each patient to compare the effect of RR on rectal doses. PTW-31014 Pinpoint chamber embedded within RR was used for in vivo dosimetry in 6 of 21 patients. The patient tolerance and acute rectal toxicity were surveyed during radiotherapy using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. RESULTS: Patients tolerated the RR well during 20 fractions with mild degree of anal irritation. Using a RR significantly reduced the rectal wall (RW), anterior RW and posterior RW dose-volume parameters. The average RW Dmean was 29.4 and 43.0 Gy for plans with and without RR, respectively. The mean discrepancy between the measured dose and planned dose was -3.8% (±4.9%). Grade 1 diarrhea, rectal urgency and proctitis occurred in 4, 2 and 3 cases, respectively. There were no grade ≥2 acute rectal toxicities during the treatment. CONCLUSION: Rectal retraction resulted in a significant reduction of rectal doses with a safe toxicity profile, which may reduce rectal toxicity. Dosimeter inserted into the RR providing a practical method for in vivo dosimetric verification. Further prospective clinical studies will be necessary to demonstrate the clinical advantage of RR.

Randomized, double-blind, placebo-controlled phase II trial of nanocurcumin in prostate cancer patients undergoing radiotherapy.

Clinical potential of curcumin in radiotherapy (RT) setting is outstanding and of high interest. The main purpose of this randomized controlled trial (RCT) was to assess the beneficial role of nanocurcumin to prevent and/or mitigate radiation-induced proctitis in prostate cancer patients undergoing RT. In this parallel-group study, 64 eligible patients with prostate cancer were randomized to receive either oral nanocurcumin (120 mg/day) or placebo 3 days before and during the RT course. Acute toxicities including proctitis and cystitis were assessed weekly during the treatment and once thereafter using CTCAE v.4.03 grading criteria. Baseline-adjusted hematologic nadirs were also analyzed and compared between the two groups. The patients undergoing definitive RT were followed to evaluate the tumor response. Nanocurcumin was well tolerated. Radiation-induced proctitis was noted in 18/31 (58.1%) of the placebo-treated patients versus 15/33 (45.5%) of nanocurcumin-treated patients (p = 0.313). No significant difference was also found between the two groups with regard to radiation-induced cystitis, duration of radiation toxicities, hematologic nadirs, and tumor response. In conclusion, this RCT was underpowered to indicate the efficacy of nanocurcumin in this clinical setting but could provide a considerable new translational insight to bridge the gap between the laboratory and clinical practice.

Machine learning-based radiomic models to predict intensity-modulated radiation therapy response, Gleason score and stage in prostate cancer.

OBJECTIVE: To develop different radiomic models based on the magnetic resonance imaging (MRI) radiomic features and machine learning methods to predict early intensity-modulated radiation therapy (IMRT) response, Gleason scores (GS) and prostate cancer (Pca) stages. METHODS: Thirty-three Pca patients were included. All patients underwent pre- and post-IMRT T2-weighted (T2 W) and apparent diffusing coefficient (ADC) MRI. IMRT response was calculated in terms of changes in the ADC value, and patients were divided as responders and non-responders. A wide range of radiomic features from different feature sets were extracted from all T2 W and ADC images. Univariate radiomic analysis was performed to find highly correlated radiomic features with IMRT response, and a paired t test was used to find significant features between responders and non-responders. To find high predictive radiomic models, tenfold cross-validation as the criterion for feature selection and classification was applied on the pre-, post- and delta IMRT radiomic features, and area under the curve (AUC) of receiver operating characteristics was calculated as model performance value. RESULTS: Of 33 patients, 15 patients (45%) were found as responders. Univariate analysis showed 20 highly correlated radiomic features with IMRT response (20 ADC and 20 T2). Two and fifteen T2 and ADC radiomic features were found as significant (P-value ≤ 0.05) features between responders and non-responders, respectively. Several cross-combined predictive radiomic models were obtained, and post-T2 radiomic models were found as high predictive models (AUC 0.632) followed by pre-ADC (AUC 0.626) and pre-T2 (AUC 0.61). For GS prediction, T2 W radiomic models were found as more predictive (mean AUC 0.739) rather than ADC models (mean AUC 0.70), while for stage prediction, ADC models had higher prediction performance (mean AUC 0.675). CONCLUSIONS: Radiomic models developed by MR image features and machine learning approaches are noninvasive and easy methods for personalized prostate cancer diagnosis and therapy.

Fiducial markers in prostate cancer image-guided radiotherapy.

Background: Image-guided radiotherapy (IGRT) is recommended to reduce the risk of geometrical miss when modern radiotherapy technologies with high grades of conformity are used. The purpose of this study was to evaluate the efficacy of fiducial markers (FMs) for electronic portal imaging in prostate cancer radiotherapy in term of evaluating the complications associated with FMs implantation, quantifying inter-fraction prostate motion, and determination of optimal planning target volume (PTV) margins. Methods: In this single institution, prospective, consecutive study, 27 patients underwent implantation of three-gold seed FMs into the prostate gland before prostate radiotherapy. Prior to computed tomography planning, all patients were asked to report any complication associated with FMs implantation that have experienced to date. Daily pre-treatment electronic portal images were captured, and prostate position errors were corrected if they were greater than 2 mm along three translational directions. Optimal PTV expansions were computed using van Herk formula [PTV-margin= 2.5Σ + 0.7σ]. Results: FMs implantation was successful with an acceptable toxicity profile in all patients. Without IGRT, margins of 5.4 mm, 5.8 mm and 5.5 mm, in vertical, longitudinal and lateral directions, respectively, are needed for a 95% confidence level of complete clinical target volume (CTV) coverage in each treatment session. The PTV margins of 3.0 mm, 3.3 mm and 4.0 mm in corresponding directions were calculated when FMs based electronic portal imaging was applied. Conclusion: FMs based electronic portal imaging is an effective tool for prostate cancer IGRT.

Development of a simplified multivariable model to predict neutropenic complications in cancer patients undergoing chemotherapy.

PURPOSE: Neutropenic complications remain the major dose-limiting toxicities of cancer chemotherapy. The aim of this study was to develop and internally validate a comprehensive and easily measurable scoring system for prediction of severe or febrile neutropenia in the first chemotherapy cycle of patients with solid tumors or lymphoma. METHODS: This prospective cohort study included consecutive patients at a tertiary referral hospital. Many clinical and laboratory-independent variables were measured at baseline. A multivariable logistic regression analysis was applied after unadjusted analysis, and the multivariable model was transformed into a simplified risk score based on 6 bootstrapped regression coefficients. The simplified scoring system was internally validated using cross-validation. All statistical tests were two-sided. RESULTS: A total of 305 patients were enrolled and followed during 1732 chemotherapy cycles. Of these, 259 were eligible for analysis. The multivariable model revealed 6 predictive factors for severe or febrile neutropenia (scores in parentheses): high-risk regimen without colony-stimulating factor (4 points), intermediate-risk regimen without colony-stimulating factor (3 points), age > 65 years and elevated ferritin (3 points), body mass index < 23 kg/m2 and body surface area < 2 m2 (2 points), estimated glomerular filtration rate < 60 mL/min/1.73m2 (2 points), and elevated C-reactive protein (1 point). The receiver operating characteristic curve was 0.832 (95% confidence interval [Cl], 0.767-0.897) for the simplified model and 0.816 (95% Cl, 0.771-0.860) for the cross-validation. CONCLUSIONS: We developed and internally validated a user-friendly prediction model to guide personalized decision-making using available clinical data and few cost-effective laboratory tests. External validation in other centers with different patients is required.

Reduction in radiation-induced lymphocytopenia by famotidine in patients undergoing radiotherapy for prostate cancer.

BACKGROUND: Ionizing radiation causes a series of hematological alterations especially profound lymphocytopenia during and after the radiotherapy course. To investigate whether famotidine can reduce hematologic toxicity in patients treated with radiotherapy for prostate cancer. METHODS: A total of 36 patients undergoing radiotherapy for prostate cancer were randomized to receive either placebo or famotidine tablets. Participants were pretreated with 40 mg of oral famotidine or placebo tablets twice daily, 4 and 3 hr before each radiotherapy fraction. The patients received external-beam radiotherapy up to 70 Gy. Complete blood counts with differential, platelet counts, and hemoglobin levels were obtained at baseline, biweekly during the treatment and once 4 weeks after the end of radiotherapy course. Magnitude of changes from baseline in the hematological parameters was determined and compared using Repeated Measures ANOVA. RESULTS: Famotidine was well tolerated. A total of 112 blood samples were evaluated. A significant reduction in radiation-induced lymphocytopenia was noted in patients receiving famotidine than in patients receiving placebo (P = 0.006). No significant difference was observed between two groups for the decline in platelets, erythrocytes and leucocytes. For both groups, neutrophil, monocyte, eosinophil, and hemoglobin levels did not change significantly during the treatment. CONCLUSIONS: Our results indicate that famotidine could result in a significant reduction in radiation-induced lymphocytopenia and may consequently increase radiotherapy efficacy as well as survival times. This radioprotective effect may be chiefly associated with its antioxidant and radical scavenging properties. Further studies are required to confirm these encouraging results.

Introducing new plan evaluation indices for prostate dose painting IMRT plans based on apparent diffusion coefficient images.

BACKGROUND: Dose painting planning would be more complicated due to different levels of prescribed doses and more complex evaluation with conventional plan quality indices considering uniform dose prescription. Therefore, we tried to introduce new indices for evaluating the dose distribution conformity and homogeneity of treatment volumes based on the tumoral cell density and relative volumes of each lesion in prostate IMRT. METHODS: CT and MRI scans of 20 male patients having local prostate cancer were used for IMRT DP planning. Apparent diffusion coefficient (ADC) images were imported to a MATLAB program to identify lesion regions based on ADC values automatically. Regions with ADC values lower than 750 mm2/s and regions with ADC values higher than 750 and less than 1500 mm2/s were considered CTV70Gy (clinical tumor volume with 70 Gy prescribed dose), and CTV60Gy, respectively. Other regions of the prostate were considered as CTV53Gy. New plan evaluation indices based on evaluating the homogeneity (IOE(H)), and conformity (IOE(C)) were introduced, considering the relative volume of each lesion and cellular density obtained from ADC images. These indices were compared with conventional homogeneity and conformity indices and IOEs without considering cellular density. Furthermore, tumor control probability (TCP) was calculated for each patient, and the relationship of the assessed indices were evaluated with TCP values. RESULTS: IOE (H) and IOE (C) with considering cellular density had significantly lower values compared to conventional indices and IOEs without considering cellular density. (P < 0.05). TCP values had a stronger relationship with IOE(H) considering cell density (R2 = -0.415), and IOE(C) without considering cell density (R2 = 0.624). CONCLUSION: IOE plan evaluation indices proposed in this study can be used for evaluating prostate IMRT dose painting plans. We suggested to consider cell densities in the IOE(H) calculation formula and it's appropriate to calculate IOE(C) without considering cell density values.

Oncological Outcomes of Neoadjuvant Gemcitabine plus Carboplatin versus Gemcitabine plus Cisplatin in Locally Advanced Bladder Cancer: A Retrospective Analysis.

PURPOSE: Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care in non-metastatic muscle-invasive bladder cancer (MIBC). There are limited data regarding the alternative choices for cisplatin-ineligible patients. This study has investigated the oncological outcomes of gemcitabine plus cisplatin (Gem/Cis) and gemcitabine plus carboplatin (Gem/Carbo) in this setting. MATERIALS AND METHODS: One hundred forty consecutive patients with MIBC (cT2-T4a) receiving neoadjuvant Gem/Cis or Gem/Carbo before chemoradiation (CRT) or radical cystectomy (RC) were retrospectively evaluated between April 2009 and April 2019. Patients with ECOG performance status 2, creatinine clearance < 60 mL/min, hydronephrosis, ejection fraction < 50%, or single kidney received Gem/Carbo. The complete clinical response (cCR) and overall survival (OS) of NAC regimens were compared. Prognostic significance was assessed with Cox proportional hazards model. RESULTS: In total, 79 patients (56.4%) received Gem/Cis. The cCR was not significantly different between Gem/Cis and Gem/Carbo regimens (38.7% vs. 36.2%, P = .771). After NAC, 79 patients (56.4%) received CRT, and other cases underwent RC. After a median follow-up of 43 months, patients in the Gem/Cis group had significantly better OS than Gem/Carbo (median OS: 41.0 vs. 26.0 months, P = .008). Multivariable Cox proportional hazards models identified cT4a stage (95% confidence interval [95% CI]: 1.001-4.85, hazard ratio [HR] = 2.08, P = .03) and cCR (95% CI: 0.26-0.99, HR = 0.51, P = .04) as the only independent prognostic factors of OS, and ruled out the type of NAC regimen. CONCLUSION: The choice of NAC (between Gem/Cis and Gem/Carbo) is not the predictor of survival and both regimens had similar cCR.

Efficacy of lettuce seed syrup on insomnia in patients with breast cancer: a pilot double blind randomized placebo controlled clinical trial.

OBJECTIVES: Insomnia and sleep disorders are common and can be severe amongst patients with cancer, especially during chemotherapy. The aim of this study was to evaluate the efficacy of lettuce seed syrup in breast cancer patients who suffer from insomnia or disordered sleep. METHODS: This pilot study was a double-blinded randomized controlled clinical trial conducted in Shoha-e-Tajrish Hospital (Tehran, Iran) from September 2018 to June 2019. 50 adult patients with breast cancer with insomnia or sleep disorders were enrolled. Participants were randomly allocated to lettuce seed syrup (5 mL twice daily), or placebo syrup at the same dose for four weeks. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality before and after the intervention. RESULTS: Compared to placebo, the mean of the total PSQI score decreased significantly in participants who received lettuce seed syrup (p=0.014). In addition, there were statistically significant reductions in the mean scores of subject quality sleep (p=0.002), sleep duration (p=0.038), habitual sleep efficacy (p=0.029) and sleep disturbance (p=0.032) in patients who received lettuce seed syrup. CONCLUSIONS: Lettuce seed syrup may improve self-reported sleep quality in participants with breast cancer. Larger trials are indicated in diverse samples of participants with caner to learn if these finds are generalizable.

Randomized, Double-blind Pilot Study of Nanocurcumin in Bladder Cancer Patients Receiving Induction Chemotherapy.

PURPOSE: To evaluate the feasibility and potential efficacy of nanocurcumin supplementation in patients with localized muscle-invasive bladder cancer (MIBC) undergoing induction chemotherapy. MATERIALS AND METHODS: In this double-blind, placebo-controlled trial, 26 MIBC patients were randomized to receive either nanocurcumin (180 mg/day) or placebo during the course of chemotherapy. All patients were followed up to four weeks after the end of treatment to assess the complete clinical response to the chemotherapy as primary endpoint. Secondary endpoints were the comparisons of chemotherapy-induced nephrotoxicity, hematologic nadirs, and toxicities between the two groups. Hematologic nadirs and toxicities were assessed during the treatment. RESULTS: Nanocurcumin was well tolerated. The complete clinical response rates were 30.8 and 50% in the placebo and nanocurcumin groups, respectively. Although nanocurcumin was shown to be superior to placebo with respect to complete clinical response rates as the primary endpoint, there was no significant difference between the groups (p = 0.417). No significant difference was also found between the two groups with regard to grade 3/4 renal and hematologic toxicities as well as hematologic nadirs. CONCLUSION: These preliminary data indicate the feasibility of nanocurcumin supplementation as a complementary therapy in MIBC patients and support further larger studies. Moreover, a substantial translational insight to fill the gap between the experiment and clinical practice in the field is provided.

Rectal wall sparing effect of a rectal retractor in prostate intensity-modulated radiotherapy.

PURPOSE: The objective of the study was to evaluate the effectiveness of a rectal retractor (RR) designed to protect rectal tissue in intensity-modulated radiotherapy (IMRT) by pushing rectal wall (RW) away from the prostate. MATERIALS AND METHODS: Twelve patients with localized prostate cancer were enrolled into this study. Patients underwent two computed tomography (CT) scans without and with RR. A prescription of 80 Gy in 40 fractions was planned on CT scans with and without RR. This study evaluates the ability of the RR in RW dose reduction, in particular reduction of the RW V70Gy≥ 25% in comparison with the plan without RR dose-volume histograms were generated with and without RR. The patient's tolerance was assessed by patient-reported outcomes. RESULTS: The planning target volume coverage was equal for both without and with RR (P = 0.155). The mean dose to the RW was statistically significantly lower for the plan with RR than that for the plan without RR, a mean reduction of 5.8 Gy (P = 0.003). Significant relative reductions in rectal dose-volume parameters whether in absolute volume (cc) or as a percentage of contoured RW were detected. A relative reduction more than 25% in RW V70Gy(%) in 100% of patients was achieved. The rectal retraction resulted in a significant increase in the prostate to the rectum space at the prostate midgland level, an absolute increase of 2.7 mm. The retraction of the rectum induced a mean (±standard deviation) pain score of 2.7 (±1.3) according to the visual analog score. CONCLUSION: The application of a RR showed a remarkable rectal sparing effect during prostate IMRT. This may lead to reduced acute and late rectal toxicities in prostate IMRT.

The feasibility of a dose painting procedure to treat prostate cancer based on mpMR images and hierarchical clustering.

BACKGROUND: We aimed to assess the feasibility of a dose painting (DP) procedure, known as simultaneous integrated boost intensity modulated radiation Therapy (SIB-IMRT), for treating prostate cancer with dominant intraprostatic lesions (DILs) based on multi-parametric magnetic resonance (mpMR) images and hierarchical clustering with a machine learning technique. METHODS: The mpMR images of 120 patients were used to create hierarchical clustering and draw a dendrogram. Three clusters were selected for performing agglomerative clustering. Then, the DIL acquired from the mpMR images of 20 patients were categorized into three groups to have them treated with a DP procedure being composed of three planning target volumes (PTVs) determined as PTV1, PTV2, and PTV3 in treatment plans. The DP procedure was carried out on the patients wherein a total dose of 80, 85 and 91 Gy were delivered to the PTV1, PTV2, and PTV3, respectively. Dosimetric and radiobiologic parameters [Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP)] of the DP procedure were compared with those of the conventional IMRT and Three-Dimensional Conformal Radiation Therapy (3DCRT) procedures carried out on another group of 20 patients. A post-treatment follow-up was also made four months after the radiotherapy procedures. RESULTS: All the dosimetric variables and the NTCPs of the organs at risks (OARs) revealed no significant difference between the DP and IMRT procedures. Regarding the TCP of three investigated PTVs, significant differences were observed between the DP versus IMRT and also DP versus 3DCRT procedures. At post-treatment follow-up, the DIL volumes and apparent diffusion coefficient (ADC) values in the DP group differed significantly (p-value < 0.001) from those of the IMRT. However, the whole prostate ADC and prostate-specific antigen (PSA) indicated no significant difference (p-value > 0.05) between the DP versus IMRT. CONCLUSIONS: The results of this comprehensive clinical trial illustrated the feasibility of our DP procedure for treating prostate cancer based on mpMR images validated with acquired patients' dosimetric and radiobiologic assessment and their follow-ups. This study confirms significant potential of the proposed DP procedure as a promising treatment planning to achieve effective dose escalation and treatment for prostate cancer. TRIAL REGISTRATION: IRCT20181006041257N1; Iranian Registry of Clinical Trials, Registered: 23 October 2019, https://en.irct.ir/trial/34305 .

Development and immunohistochemical characterization of patient-derived xenograft models for muscle invasive bladder cancer.

Objectives: Patient-derived xenograft (PDX) models have become a valuable tool to evaluate chemotherapeutics and investigate personalized cancer treatment options. The role of PDXs in the study of bladder cancer, especially for improvement of novel targeted therapies, continues to expand. In this study, we aimed to establish autochthonous PDX models of muscle-invasive bladder cancer (MIBC) to provide a useful tool to conduct research on personalized therapy. Materials and Methods: Tumors from MIBC patients undergoing radical cystectomy were subcutaneously transplanted into immunodeficient mice. The tumor size was measured by a caliper twice a week for up to five months. After the first growth in mice, they were serially passaged. Hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) of 11 markers (Ki67, P63, GATA3, KRT5/6, KRT20, E-cadherin, 34ßE12, PD-L1, EGFR, Nectin4, and HER2) were used to evaluate phenotype maintenance of original tumors. Results: From 10 MIBC patients, two PDX models (P8X20 and P8X26) were successfully established (20% success rate). These models mostly retained primary tumor characteristics including histology, morphology, and molecular nature of the original cancer tissues. IHC analysis showed that the expression level of 7 markers for the model P8X20, and 8 markers for the model P8X26 was exactly similar between the patient tumor and the next generations. Conclusion: We developed the first autochthonous PDX models of MIBC in Iran. Our data suggested that the established MIBC PDX models reserved mostly histopathological characteristics of primary cancer and could provide a new tool to evaluate novel biomarkers, therapeutic targets, and drug combinations.

Relationship between perceived social support and psychological hardiness with family communication patterns and quality of life of oncology patients.

AIM: The purpose of this study was to determine the relationship between PSS, PH, FCP and QoL of oncology patients. METHODS: In this descriptive-correlational study, 340 oncology patients were selected with convenience sampling method from the hospitals in Tehran 2018-2019. Data were collected using, "PSS," "PH," "FCP" and "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, EORTC QLQ-C30." Data were analysed using descriptive and inferential statistics using SPSS21 and Amos. RESULTS: The direct effect and the total effect of PSS and FCP on QoL were significant (p < .001), but their indirect effect was not significant (p > .05) and the effect of PH on QoL was not significant (p = .96). The Root Mean Squares of Error Approximations (RMSEA), Non-Normed Fit Index (NNFI), Comparative Fit Index (CFI) and Goodness of Fit Index (GFI) were estimated 0.07, 0.97, 0.98 and 0.91, respectively.