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Mahonia leschenaultia takeda (Berberidaceae) (MLT) is a traditional medicinal plant that is commonly used to treat and improve liver and renal conditions in India and other Asian countries. Acetaminophen (APAP) is commonly used as an analgesic and an antipyretic agent that, in high doses, produces liver and kidney necrosis in mammals. The aim of this study was to investigate the nephroprotective and antioxidant activities of the ethanol extract of MLT at two dose levels of 250 and 500 mg kg-1 bw on APAP-induced toxicity in rats. APAP significantly increased levels of serum urea, hemoglobin (Hb), total leukocyte count, creatinine, packed cell volume, DLC, and mean corpuscular volume, raised body weight, and reduced levels of neutrophils, mean corpuscular Hb content, mean corpuscular hematocrit, granulocytes, uric acid, and platelet concentration. MLT inhibited the hematological effects of APAP. MLT significantly increased activities of renal superoxide dismutase, catalase, glutathione, and glutathione peroxidase and decreased malondialdehyde content of APAP-treated rats. Apart from these, histopathological changes also showed the protective nature of the MLT extract against APAP-induced necrotic damage of renal tissues. In conclusion, data suggest that the ethanol extract of MLT prevented renal damage from APAP-induced nephrotoxicity in rats and it is likely mediated through antioxidant activities. [ABSTRACT FROM AUTHOR]

Introduction: Cancer patients are increasingly incorporating medical marijuana into the management of treatment-related side effects. Currently however, data is limited regarding the risks and benefits of therapeutic cannabis for cancer patients. We sought to characterize radiation oncologists' practices and opinions regarding therapeutic cannabis via a nationwide survey., Materials and Methods: An anonymous survey was distributed via email to 873 radiation oncologists in the American Society for Radiation Oncology member database. Radiation oncologists were asked their opinions and practices regarding the use of therapeutic cannabis for their patients. Bivariate analyses of potential predictors for responses were conducted using standard statistical techniques., Results: One hundred seven radiation oncologists completed the survey. According to the survey, 36% of respondents would recommend therapeutic cannabis to their patients to mitigate treatment toxicity. Physicians practicing in states where medical marijuana is legal were more likely to recommend it compared to physicians working in states that have not legalized medical marijuana (OR = 3.79, 1.19-12.1, p = 0.01). Seventy-one percent of respondents reported therapeutic cannabis as being effective at least some of the time for managing treatment-related toxicities. Fifty-eight percent of physicians reported lacking sufficient knowledge to advise patients regarding therapeutic cannabis, while 86% of respondents were interested in learning more about therapeutic cannabis for cancer patients., Conclusions: Although a majority of radiation oncologists believe there are benefits to therapeutic cannabis, many are hesitant to recommend for or against its use. Radiation oncologists appear to be interested in learning more about how therapeutic cannabis may play a role in their patients' care., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Neoadjuvant chemoradiation, followed by esophagectomy, is a standard of care for locally advanced esophageal cancers. The ChemoRadiOtherapy plus Surgery versus Surgery alone (CROSS) trial reported a 30-day mortality rate of 6%. We sought to evaluate 30- and 90-day mortality in similar patients in the United States and identify predictors of higher mortality rates., Methods: The National Cancer Database was used to identify patients with cT3-4/N+ esophageal cancers treated with neoadjuvant chemoradiation followed by esophagectomy. Bivariate univariable and multivariable regression analysis was used to identify predictors of 30- and 90-day mortality., Results: We identified 7691 patients. Readmission within 30 days of surgery occurred in 6.0% of patients. Mortality was 2.9% at 30 days and 7.2% at 90 days. Positive surgical margins conferred a more than doubled risk of 30- and 90-day mortality, 5.5% vs 2.7% and 14.6% vs 6.8% (both P < .001). Facility surgical volume impacted 30-day mortality, whereas readmission was associated with 90-day mortality, both exceeding 10% (P = .004 and P = .001, respectively). In patients undergoing minimally invasive surgery converted to open, 90-day mortality was 12.1% (P < .01). For patients 69 years and older, 90-day mortality was also 12.1% (P < .001). Patients who underwent esophagectomy more than 45 days from completion of chemoradiation also had higher 90-day mortality at 8.3% vs 6.2% (P < .001)., Conclusions: Postoperative death at 30 and 90 days after neoadjuvant chemoradiation and esophagectomy appears to be on par with randomized data. Positive surgical margins, squamous cell carcinomas, age 69 and older, readmission within 30 days, and conversion from a minimally invasive operation to an open operation all carry a 90-day mortality risk exceeding 10%., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Given the relative novelty of stereotactic body radiation therapy as a treatment modality low-risk and intermediate-risk prostate cancer, little data exist evaluating dosimetry and its impact on patient-reported quality of life (PR-QOL) metrics. Herein, we present an interim analysis of a phase II clinical trial of PR-QOL and dosimetric correlates., Methods: Patients with biopsy-proven low-risk or intermediate-risk prostate cancer, prostate volume ≤100 cm, and life expectancy ≥10 years were enrolled. Expanded Prostate Cancer Index Composite (EPIC) scores were tabulated by domain and evaluated in relation to dosimetry. Paired t test was performed to compare differences in scores from baseline. Minimally important differences were established using the anchor-based approach and correlations made using the χ test., Results: A total of 95 patients were analyzed with a median follow-up of 18.1 months (range, 3.0 to 76.9 mo). There were no cases of acute or late grade 3+ GI or GU toxicities. Expanded Prostate Cancer Index Composite scores in urinary obstructive/irritative domain at 1 month (-4.8, P=0.03) and bowel domain at 1, 6, and 12 months (-10.8, -6.1, and -5.2) were significantly different from pretreatment, with both returning to nonsignificant differences around 24 months. Higher bladder V37Gy (≥3.35%) was associated with both late urinary incontinence and obstructive/irritative declines. Both higher rectal D5% and rectal V36Gy >0.6 cm were correlated with an enhanced proportion of patients with late minimally important difference declines., Conclusions: Higher dose volumes for the bladder and rectum predicted for poorer PR-QOL. In contrast to prostate brachytherapy data, neither prostate volume nor urethral dosimetry at this dose schedule correlated with urinary symptoms.

Purpose: Per American Brachytherapy Society guidelines, cT1-2N0 penile cancers <4 cm in diameter are excellent candidates for curative brachytherapy. Using that criterion, we evaluated national patterns of care and predictors of use of radiation techniques using the National Cancer Database., Methods and Materials: The National Cancer Database was queried for men with cT1-2N0 penile cancers <4 cm in size. Comparative statistics for treatment modality were generated using bivariate logistic regression analysis., Results: Among 1235 cases eligible for analysis, median age was 69 years. Median tumor size was 2.0 cm. 95.8% of men underwent surgery alone, with 91 (7.4%) undergoing radical penectomy, 673 (54.5%) partial penectomy, and 419 (33.9%) cosmesis-preserving surgical procedure. Only 4 (0.3%) men were treated with brachytherapy alone, 48 (3.9%) with external-beam radiation therapy (EBRT) alone, and 8 (0.6%) with EBRT after surgery. Surgical margins were positive in 118 (9.6%) patients, 14 of whom received adjuvant EBRT (11.9%) and two adjuvant brachytherapy (1.7%). There was no difference in demographic or clinical characteristics in groups treated with surgery vs. radiation (all p > 0.2). Age >70, lesions >2 cm, and T2 tumors were more likely to undergo non-organ-preserving therapy vs. radiation or a cosmesis-preserving procedure (all p < 0.05). The propensity-matched 5-year survival was not different between definitive radiation vs. surgery (61.6% vs. 62.2%, p = 0.70)., Conclusions: Men with penile-preserving eligible lesions in the United States are overwhelmingly treated with surgery. Penile-preserving radiation techniques including brachytherapy and EBRT are underutilized and should be offered as curative interventions., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Recent Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology guidelines recommend that the dose to 90% (D90) of the high-risk clinical target volume (HRCTV) in cervical cancer be at least 85 Gy, with higher doses for poor response to radiation therapy., Methods and Materials: A retrospective review of brachytherapy delivered at a single institution was evaluated for dosimetry and outcomes. Significance of tumor parameters on local control was evaluated with Kaplan-Meier and univariable and multivariable Cox regression analysis. Correlations were determined with a linear regression model., Results: A total of 239 women underwent high-dose-rate brachytherapy for cervical cancer between 2007 and 2018 with evaluable dosimetry. Median follow-up was 28.6 months. The median prescribed dose was 27.5 Gy in 5 fractions, with a median HRCTV D90 of 83.9 Gy (range, 81.9-85.7 Gy), HRCTV volume of 31 cm 3 (range, 14.9-121.9 cm 3 ), and treatment time of 51 days (range, 36-83 days). Local control for the entire cohort at 5 years was 90.8%. Local control was worse with adenocarcinomas, HRCTV >40 cm 3 at brachytherapy, requirement for a higher brachytherapy dose, and treatment >51 days. On multivariable analysis, local control was worse with adenocarcinoma (hazard ratio, 4.141; 95% confidence interval, 1.498-11.444; P = .006) and HRCTV >40 cm 3 (hazard ratio, 3.640; 95% confidence interval, 1.316-10.069; P = .013). HRCTV EQD2 D90 > 85 Gy did not statistically improve outcomes for any subset. The 2-year progression-free survival for HRCTV >40 cm 3 was 66.2% versus 84.1% if ≤40 cm 3  (P < .001). Overall survival was predicted by HRCTV and overall treatment time in multivariable analysis. For women with HRCTV ≤40 cm 3 , overall survival at 2 years was 90.4% versus 68.5% if >40 cm 3  (P < .001)., Conclusion: Local control was excellent with magnetic resonance imaging-based planning in the entire cohort of patients. A poor response to external beam radiation (larger HRCTV) and adenocarcinoma histology predicted for worse local control despite association with higher brachytherapy prescription. Women with these risk factors face higher rates of extrapelvic progression and poorer overall survival., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Despite multimodal treatment for high-grade gliomas, prognosis remains grim. Prior Radiation Therapy Oncology Group-Recursive Partitioning Analysis (RTOG-RPA) reports indicate based on pretreatment and treatment-related factors, a subset of patients experience a significantly improved survival. Since the development of the RTOG-RPA, high-grade gliomas have seen the widespread introduction of temozolomide and tumor oncogenetics. Here we aimed to determine whether the RTOG-RPA retained prognostic significance in the context of modern treatment, as well as generate an updated RPA incorporating both clinical and genetic variables., Methods: Patients with histologically proven glioblastoma, gliosarcoma, anaplastic astrocytoma, and anaplastic oligodendroglioma treated with intensity-modulated radiation therapy (IMRT) between 2004 and 2017 were reviewed. The primary endpoint was overall survival from date of diagnosis. Primary analysis compared actual survival rates to that expected of corresponding RTOG-RPA class. Secondary analysis utilized the rpart function to recursively partition overall survival by numerous clinical and genetic pretreatment and treatment-related variables. A tertiary analysis recursively partitioned a subset of patients in which the status of all genetic markers were known., Results: We identified 878 patients with histologically proven high-grade glioma treated with IMRT and 291 patients in our genetic subset. Median overall survival for the entire cohort was 14.2 months (95% confidence interval, 13.1-15.3). Applying the RTOG-RPA to our cohort validated the relative prognostic ordering of the survival classes except class II. Generating our new RPA created 7 significantly different survival classes (P<0.001, χ=584) with median survival ranging from 96.4 to 2.9 months based on age, histology, O6-methylguanine-DNA methyltransferase methylation status, radiation fractions, tumor location, radiation dose, temozolomide status, and resection status. Our second RPA of our genetic subset generated 5 significantly different survival classes (P<0.001, χ=166) with survival ranging from 65.3 to 5.6 months based on age, isocitrate dehydrogenase 1 mutation status, O6-methylguanine-DNA methyltransferase methylation status, neurological functional classification, hospitalization during IMRT, temozolomide status, and Karnofsky performance status., Conclusions: The RTOG-RPA retains partial prognostic significance, however, should be updated to reflect recent advancements. This series represents a large RPA analyzing both clinical and genetic factors and generated 7 distinct survival classes. Further assessment of patients with fully available genetic markers generated 5 distinct survival classes. These survival classifications need to be validated by a prospective data set and compared against the RTOG-RPA to determine whether they provide improved prognostic power.

Purpose: Oligometastatic disease has emerged as a potentially curable state in the spectrum of cancer progression. Aggressive local therapy such as stereotactic ablative radiation therapy (SABR) may improve oncologic outcomes. Herein, we report the initial oncologic outcomes and patient-reported quality of life (PR-QoL) from a phase 2 multicenter trial for patients with oliogmetastatic disease., Methods and Materials: Patients with oligometastatic disease (1-5 metastases) were prospectively recruited between 2011 and 2017. SABR dose and fractionation was dependent on the lesion size and location. Patient follow-up occurred within 6 weeks of completion of SABR and at 3-month intervals. Patients received a Functional Assessment of Cancer Therapy-General questionnaire at baseline and at each follow-up to assess for PR-QoL. Median follow-up was calculated by reverse Kaplan-Meier method. Overall survival (OS), local progression-free survival, and distant progression-free survival were calculated using the Kaplan-Meier method., Results: We enrolled 147 patients with oligometastatic cancer with a median age of 66.4 years (interquartile range, 59.9-74.6). The most common primary tumors included lung (21.8%, non-small cell: n = 29, small cell: n = 3), colorectal adenocarcinoma (21.1%), and head and neck (10.9%, squamous cell carcinoma: n = 11). In a median follow-up of 41.3 months (interquartile range: 14.6-59.0), the median OS was 42.3 months (95% confidence interval: 27.4-∞) with 5-year OS of 43%. Five-year local progression-free survival and distant progression-free survival were 74% and 17%, respectively. Acute grade 2+ and 3+ toxicity were 7.5% and 2.0%, respectively, and late grade 2+ and 3+ toxicity were both 1.4%. There was no significant change in quality of life at completion and 6 weeks, 3 months, and 9 months after treatment. At 6 and 12 months, patients were found to have statistically significant improvement in PR-QoL., Conclusions: This multicenter prospective phase 2 study demonstrates that SABR for recurrent oligometastatic cancer is a feasible and tolerable treatment option with minimal acute and late grade 3 toxicity. Additionally, PR-QoL was not adversely affected., (Copyright © 2018. Published by Elsevier Inc.)

Purpose: To investigate the correlation between positron emission tomography/computed tomography (PET/CT) response and outcome in the era of magnetic resonance imaging (MRI)-based planning and to assess whether the addition of diffusion-weighted MRI (DW-MRI) could more accurately classify treatment response and prognosis., Methods and Materials: A retrospective chart review identified 244 consecutive patients with International Federation of Gynecology and Obstetrics stage IB1-IVA cervical cancer treated with concurrent chemoradiation, including high-dose-rate image-based brachytherapy, between 2007 and 2016. Image-based brachytherapy was delivered with 5 intracavitary/interstitial fractions, each 5 to 6 Gy per fraction., Results: An complete response on posttreatment PET/CT (PET-CR) was discovered in 50 of 244 patients (20%) at a median interval of 3.3 months (range, 2.1-7.7 months) after treatment. After a median follow-up of 27 months, 2-year overall survival was 83% in all patients. Metabolic response significantly impacted 2-year overall survival (94% complete response on posttreatment PET/ CT vs 62.4% PET-IR, P < .001). Of those with a PET-IR, 16 of 50 patients (32%) suffered a local recurrence. A total of 27 of 50 patients with a PET-IR underwent DW-MRI; 11 of 27 posttreatment DW-MRI scans (40%) were interpreted as positive by central review (median apparent diffusion coefficient of 0.973 × 10 -3  mm 2 /s). Of the DW-MRI-positive patients, 9 of 11 (81.8%) suffered a histologically confirmed local recurrence, and 2 of 11 patients are without evidence of disease. Additionally, 16 of 27 DW-MRI studies were interpreted as negative, and 2 of 16 (12.5%) of these patients suffered a local recurrence. Diffusion-weighted MRI findings significantly impacted 2-year overall survival (83% negative DW-MRI vs 36% positive DW-MRI, P = .049)., Conclusion: Incomplete PET/CT response was documented in 20% of patients after image-based brachytherapy for locally advanced cervical cancer. Integration of DW-MRI helped accurately identify patients at risk for persistent disease and worse long-term outcome. The value of DW-MRI requires further validation in a large prospective dataset as this modality may allow earlier evaluation and salvage treatment in those with PET-IR., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Patients with oligometastatic colorectal cancer have demonstrated excellent clinical outcomes with surgical resection of hepatic and pulmonary metastases. Stereotactic ablative radiation therapy (SABR) has emerged as an alternative local therapy for nonsurgical candidates. Herein, we report the oncologic and patient-reported quality-of-life (PR-QoL) outcomes for a subset of patients with oligometastatic colorectal cancer who were treated in a prospective phase 2 multicenter clinical trial., Methods and Materials: Patients with a pathologically proven diagnosis of oligometastatic colorectal cancer were enrolled as part of a prospective study. SABR dose and fractionation schedules were dependent on the lesion location and size. Patient follow-up occurred 6 weeks after completion of SABR and at 3-month intervals for the following 3 years. Patients received the Functional Assessment of Cancer Therapy-General questionnaire at baseline and at each follow-up visit to assess PR-QoL. The total Functional Assessment of Cancer Therapy-General questionnaire scores were compared with those from baseline using the Wilcoxon signed rank test. Overall survival, local progression-free survival (PFS), and distant PFS were calculated using the Kaplan-Meier estimation to the date of the last follow-up visit/death or local/distant failure., Results: A total of 31 patients with oligometastatic colorectal cancer with 1 (71.0%), 2 (16.1%), 3 (3.2%), 4 (3.2%), or 5 (6.5%) metastatic lesions were identified. After a median follow-up time of 50.1 months, the median OS from the time of completion of the SABR was 53.9 months (95% confidence interval, 23.2-84.6), and the 5-year OS, local PFS, and distant PFS were 45%, 83%, and 27%, respectively. Acute grade 2+ toxicity was 9.7% (pain, nausea, fatigue) and late grade 3+ toxicity (small bowel obstruction) was 3.2% with no significant change in PR-QoL in the year after SABR., Conclusions: This subset analysis of a prospective phase 2 study demonstrates that SABR is a safe and effective treatment option for patients with unresectable oligometastic colorectal cancer. In addition, SABR of oligometastatic disease preserves PR-QoL.

Purpose: We report the clinical workflow and time required for MRI-based image-guided brachytherapy (MR-IGBT) of cervical cancer patients in a high-volume brachytherapy center with 10 years of experiences to provide a practical guideline for implementing MR-IGBT into clinical use., Methods and Materials: We recorded the time and workflow of each procedure step within the 40 consecutive ring and tandem applicator fractions of MR-IGBT by our multidisciplinary team. We divided the entire procedure into four sections based on where the procedure was performed: (1) applicator insertion under sedation, (2) MR imaging, (3) planning, and (4) treatment delivery. In addition, we compared the current procedure time to the initial procedure time when first implementing MR-IGBT in 2007-2008 via a retrospective review., Results: Mean total procedure time was 149.3 min (SD 17.9, ranges 112-178). The multidisciplinary team included an anesthesia team, radiologist, radiation oncologist, nurses, radiation therapists, MRI technicians, dosimetrists, and physicists. The mean procedure time and ranges for each section (min) were as follows: (1) 56.2 (28.0-103.0), (2) 31.0 (19.0-70.0), (3) 44.3 (21.0-104.0), and (4) 17.8 (9.0-34.0). Under current setting, the combined mean procedure time for MR imaging and planning was 63.2 min. In comparison, the same procedure took 137.7 min in 2007-2008 period, which was significantly longer than the current workflow (p < 0.001)., Conclusions: A skilled and dedicated multidisciplinary team is required for an efficient clinical workflow and delivery of MR-IGBT. Over the years, we have improved efficiency with clinical experience and continuous efforts in staff education., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

OBJECTIVE Akin to the nonoperative management of benign intracranial tumors, stereotactic body radiation therapy (SBRT) has emerged as a nonoperative treatment option for noninfiltrative primary spine tumors such as meningioma and schwannoma. The majority of initial series used higher doses of 16-24 Gy in 1-3 fractions. The authors hypothesized that lower doses (such as 12-13 Gy in 1 fraction) might provide an efficacy similar to that found with the dose de-escalation commonly used for intracranial radiosurgery to treat acoustic neuroma or meningioma and with a lower risk of toxicity. METHODS The authors identified 38 patients in a prospectively maintained institutional radiosurgery database who were treated with definitive SBRT for a total of 47 benign primary spine tumors between 2004 and 2016. SBRT consisted of 9-21 Gy in 1-3 fractions using the CyberKnife (n = 11 [23%]), Synergy S (n = 21 [45%]), or TrueBeam (n = 15 [32%]) radiosurgery platform. For a comparison of SBRT doses, patients were dichotomized into 1 of 2 groups (low-dose or high-dose SBRT) using a cutoff biologically effective dose (BED 10Gy ) of 30 Gy. Tumor control was calculated from the date of SBRT to the last follow-up using Kaplan-Meier survival analysis, with comparisons between groups completed using a log-rank method. To account for potential indication bias, a propensity score analysis was completed based on the conditional probabilities of SBRT dose selection. Toxicity was graded using Common Terminology Criteria for Adverse Events version 4.0 with a focus on grade 3+ toxicity and the incidence of pain flare. RESULTS For the 38 patients, the most common histological findings were meningioma (15 patients), schwannoma (13 patients), and hemangioblastoma (7 patients). The median age at SBRT was 58 years (range 25-91 years). The 47 treated lesions were located in the cervical (n = 18), thoracic (n = 19), or lumbosacral (n = 10) spine. Five (11%) lesions were lost to follow-up after SBRT. The median follow-up duration for the remaining 42 lesions was 54 months (range 1.2-133 months). Six (16%) patients (with a total of 8 lesions) experienced pain flare after SBRT; no significant predictor of pain flare was identified. No grade 3+ acute- or late-onset complication was noted. The 5-year local control rate was 76% (95% CI 61%-91%). No significant difference in local control according to dose, fractionation, previous radiation, surgery, tumor histology, age, treatment platform, planning target volume, or spine level treated was found. The 5-year local control rates for low- and high-dose treatments were 73% (95% CI 53%-93%) and 83% (95% CI 61%-100%) (p = 0.52). In propensity score-adjusted multivariable analysis, no difference in local control was identified (HR 0.30, 95% CI 0.02-5.40; p = 0.41). CONCLUSIONS Long-term follow-up of patients treated with SBRT for benign spinal lesions revealed no significant difference between low-dose (BED 10Gy ≤ 30) and high-dose SBRT in local control, pain-flare rate, or long-term toxicity.

Background/aim: Prostate cancer can be treated with radical prostatectomy (RP), external-beam radiotherapy (EBRT), or brachytherapy (BT). These modalities have similar cancer-related outcomes. We used an innovative method to analyze the cost of such treatment., Materials and Methods: We queried our Institution's Insurance Division [University of Pittsburgh Medical Center (UPMC) Health Plan] beneficiaries from 2003-2008, who were diagnosed with prostate cancer and also queried the UPMC tumor registry for all patients with prostate cancer treated at our Institution. In a de-identified manner, data from the Health Plan and Tumor Registry were merged., Results: A total of 354 patients with non-metastatic disease with treatment initiated within 9 months of diagnosis were included (RP=236, EBRT=55, and BT=63). Radiotherapy-treated patients tended to be older, higher-risk, and have more comorbidities. Unadjusted median total health care expenditures during the first year after diagnosis were: RP: $16,743, EBRT: $47,256, and BT: $23,237 (p<0.0005). A propensity score-matched model comparing RP and EBRT demonstrated median total health care expenditures during year one: RP: $8,189, EBRT: $10,081; p=0.48. In a propensity-matched model comparing RP and BT, the median total health care expenditures during year one were: RP: $18,143, BT: $26,531; p=0.015 and per year during years 2 through 5 from diagnosis were: RP: $5,913, BT: $6,110; p=0.68., Conclusion: This pilot study demonstrates the feasibility of combining healthcare costs from the payer's perspective with clinical data from a Tumor Registry within an IDFS and represents a novel approach to investigating the economic impact of cancer treatment., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)