Interstitial brachytherapy for pediatric soft tissue sarcoma: Evolving practice over three decades and long-term outcomes.

PURPOSE: Evaluate long-term clinical outcomes, adverse effects, and evolving practice of interstitial brachytherapy (BT) for pediatric soft tissue sarcomas (STS). METHODS: From September 1984 to December 2014, 105 children (median age 10 years) were included. There were 60 males and 45 females. The majority (74%) had primary lesions. Synovial sarcoma (22%) was the most frequent histology. Treatment included wide local excision and BT with or without external beam radiotherapy (EBRT). Eighty-five (81%) received BT alone. RESULTS: After a median follow-up of 65 months, local control (LC), disease-free survival (DFS), and overall survival (OS) at 10 years were 83, 66, and 73%, respectively. On univariate analysis, LC was superior with tumors <5 cm versus >5 cm (93% vs. 75%, P = 0.10), Grade I/II versus Grade III tumors (97% vs. 73%, P = 0.01), nonround cell versus round cell histology (89% vs. 72%, P = 0.03), and trunk/extremity versus head and neck/genitourinary sites (87% vs. 57%, P = 0.0001). On multivariate analysis tumor size (P = 0.03) and location (P = 0.002) retained significance. Children receiving BT alone had comparable LC to those receiving BT and EBRT (84% vs. 80%, P = 0.43). There was no difference in LC between LDR versus HDR BT (86% vs. 83%, P = 0.30). Wound complications were seen in 6%. Subcutaneous fibrosis (25%), limb edema (6%), skeletal abnormalities (3%), and neuropathy (1%) were the late complications. One child (0.9%) developed a second malignancy after 7 years. CONCLUSION: Interstitial BT with or without EBRT results in excellent outcomes. Radical BT alone, when used judiciously, results in excellent local control and function with minimal treatment-related morbidity.

TOLERABILITY AND TUMOR RESPONSE OF A NOVEL LOW-DOSE PALLIATIVE RADIATION THERAPY PROTOCOL IN DOGS WITH TRANSITIONAL CELL CARCINOMA OF THE BLADDER AND URETHRA.

Previously reported radiation protocols for transitional cell carcinoma of the canine lower urinary tract have been ineffective or associated with increased side effects. Objectives of this retrospective, cross-sectional study were to describe safety of and tumor responses for a novel palliative radiation protocol for transitional cell carcinoma in dogs. Included dogs had cytologically or histologically confirmed transitional cell carcinoma of the bladder or urethra, and were treated with 10 once-daily fractions (Monday-Friday) of 2.7 Gy. Thirteen dogs were sampled, with six treated using radiation as first-line (induction) therapy and seven treated using radiation as rescue therapy after failing previous chemotherapy. Within 6 weeks of radiation, 7.6% (1/13) dogs had a complete response, 53.8% (7/13) partial response, 38.5% (5/13) stable disease, and none had progressive disease. Three patients presenting with urethral obstruction had spontaneous micturition restored during the treatment protocol. A single patient with unilateral ureteral obstruction was patent at recheck examination. Median survival time from time of initial diagnosis was 179 days. Median survival time from start of radiation was 150 days. Acute radiation side effects occurred in 31% (4/13) patients and were classified as grade 1 or 2. No significant late side radiation side effects were reported. No variables examined were identified as prognostic factors. Findings indicated that the reported radiation protocol was safe in this sample of dogs with bladder and urethral transitional cell carcinoma. Future prospective studies are needed to determine utility of this treatment as a rescue therapy in patients with complete urinary tract obstruction.

A qualitative study of cancer survivors' responses to information on the long-term and late effects of pelvic radiotherapy 1-11 years post treatment.

As more patients survive cancer for longer term, the long-term and late effects of treatments become increasingly important issues for cancer survivors and providing information to enable survivors to recognise and manage them becomes an increasingly pressing challenge for health care professionals. The aim of this study was to explore the experiences of cancer survivors regarding information given on potential long-term and late effects of pelvic radiotherapy. Semi-structured interviews were conducted with 28 cancer survivors who had had radiotherapy to the pelvic area for a range of cancers 1-11 years previously. Participants were recruited using maximum variation sampling from a larger questionnaire survey of patients treated at one hospital. Interviews were recorded, transcribed and analysed using Framework. Participants recognised the value of information to reassure and to inform action but also its potentially undesirable effects to frighten or raise anxieties about future problems and its inherent limitations in meeting their wider needs. They identified the timing, amount of information and context in which it was given as of particular importance. Information based on personal experience was also valued. These findings highlight the importance of appropriate, individualised information during treatment, at hospital discharge and subsequently in primary care.

Radiation therapy for extramammary Paget's disease: treatment outcomes and prognostic factors.

BACKGROUND: Extramammary Paget's disease (EMPD) is a relatively rare malignancy, and there are few reports related to radiation therapy. In the present study, we investigated the outcome of radiation therapy for EMPD. PATIENTS AND METHODS: Forty-one patients with EMPD in the genitalia underwent radiation therapy with curative intent. Fifteen patients had regional lymph node metastases before radiation therapy, but none had distant metastasis. Total doses of 45-80.2 Gy (median, 60 Gy) were delivered to tumor sites in 23-43 fractions (median, 33 fractions). RESULTS: At a median follow-up period of 41 months, 16 patients had developed recurrences, including 5 with local progression within the radiation field and 12 with lymph node or/and distant metastases outside the radiation field. The local progression-free and disease-free rates were 88% and 55% at 3 years, and 82% and 46% at 5 years, respectively. Nine patients died at 6-73 months after irradiation; the causes of death were tumor progression in five patients, infectious pneumonia in two, renal failure in one and old age in one. The overall and cause-specific survival rates were 93% and 96% at 3 years, and 68% and 84% at 5 years, respectively. Tumor invasion into the dermis and regional lymph node metastasis were significant prognostic factors for both distant metastasis and survival. No therapy-related toxicities of grade ≥3 were observed. CONCLUSIONS: Radiation therapy is safe and effective for patients with EMPD. It appeared to contribute to prolonged survival owing to good tumor control, and to be a promising curative treatment option.

Ovarian transposition in prepubescent and adolescent girls with cancer.

Ovarian transposition was the first procedure proposed to preserve fertility in girls with cancer and is indicated for patients with tumours requiring pelvic radiation at doses of 42·0-58·4 Gy, much higher doses than those that can induce loss of ovarian function (4-20 Gy). Ovarian transposition is usually done after neoadjuvant chemotherapy and is completed by minimally invasive surgery or open surgery in case of concomitant resection of the abdominal tumour. According to the type of tumour, the ovaries are moved and placed in the paracolic gutters when the radiation field reaches the midline (for medulloblastoma or urogenital rhabdomyosarcoma), contralaterally to the tumour (for pelvic sarcomas), or in line with the iliac crests (for Hodgkin's lymphoma). However, in 10-14% of cases the procedure can fail to protect the ovaries. Although few long-term results in adults are available, normal hormonal function and pregnancies have been reported in a few long-term follow-up studies. In view of the continued development of fertility preservation techniques, ovarian transposition should be discussed at a multidisciplinary meeting at the time of cancer diagnosis.

Applicability of randomized trials in radiation oncology to standard clinical practice.

BACKGROUND: Randomized controlled trials (RCTs) are commonly used to inform clinical practice; however, it is unclear how generalizable RCT data are to patients in routine clinical practice. The authors of this report assessed the availability and applicability of randomized evidence guiding medical decisions in a cohort of patients who were evaluated for consideration of definitive management in a radiation oncology clinic. METHODS: The medical records of consecutive, new patient consultations between January and March 2007 were reviewed. Patient medical decisions were classified as those with (Group 1) or without (Group 2) available, relevant level I evidence (phase 3 RCT) supporting recommended treatments. Group 1 medical decisions were further divided into 3 groups based on the extent of fulfilling eligibility criteria for each RCT: Group 1A included decisions that fulfilled all eligibility criteria; Group 1B, decisions that did not fulfill at least 1 minor eligibility criteria; or Group 1C, decisions that did not fulfill at least 1 major eligibility criteria. Patient and clinical characteristics were tested for correlations with the availability of evidence. RESULTS: Of the 393 evaluable patients, malignancies of the breast (30%), head and neck (18%), and genitourinary system (14%) were the most common presenting primary disease sites. Forty-seven percent of all medical decisions (n = 451) were made without available (36%) or applicable (11%) randomized evidence to inform clinical decision making. Primary tumor diagnosis was significantly associated with the availability of evidence (P < .0001). CONCLUSIONS: A significant proportion of medical decisions in an academic radiation oncology clinic were made without available or applicable level I evidence, underscoring the limitations of relying solely on RCTs for the development of evidence-based health care.

Pelvic radiotherapy and sexual function in men and women.

INTRODUCTION: Despite the decrease in overall cancer incidence and mortality rates in developed countries since the early 1990 s, cancer remains a major public health problem. Sexual dysfunction is one of the more common consequences of cancer treatment. AIM: To shortly review the literature and level of evidence on sexual dysfunction in men and women following pelvic radiotherapy. MAIN OUTCOME MEASURES: Male and female sexual dysfunction. METHODS: Literature review. RESULTS: Sexual dysfunction in cancer patients is multidimensional and may result from biological, psychological, and social factors. Anatomic changes caused by surgery and/or radiotherapy, physiological changes following hormonal manipulation, and the secondary effect of medical intervention may impede or preclude sexual functioning, even when sexual desire is intact. Pelvic irradiation constitutes the primary or adjuvant treatment for a large number of both female and male cancers. No randomized controlled trials could be identified regarding the effect of radiotherapy on sexual dysfunction. However, prospective and clinical controlled trials all demonstrated a severe negative effect on sexual functioning in men and women following radiotherapy for a pelvic cancer. Following pelvic radiotherapy for prostate cancer, a positive effect of phosphodiesterase type 5 inhibitors on erectile dysfunction has been demonstrated, whereas no significant effect on female sexuality was found. Few studies evaluated treatment of female sexual dysfunction following radiotherapy; hormone replacement therapy and the use of vaginal dilator in combination with psycho-educational support is recommended. CONCLUSION: Pelvic radiotherapy plays a significant negative role in the complex scenario of male and female sexual dysfunction. The literature has focused on sexual dysfunction and intervention in prostate and cervical cancer patients. Sexual dysfunction following pelvic radiotherapy for cancer in other pelvic organs, e.g., bladder, rectum, and anus, requires more attention in future studies. Health care providers should pay attention to and provide psychological and medical support regarding sexual dysfunction to all patients who have received pelvic radiotherapy.

[Why is PET/CT essential in urooncology?]. / Miért kell a PET/CT az uroonkológiában?

The wide use of molecular positron emission tomography/computed tomography (PET/CT) imaging in the tumor diagnostics has been playing an important role recently. The clinical role of hybrid imaging (PET/CT, single photon ECT/CT (SPECT/CT)) is growing continuously due to the simultaneous imaging of anatomy and function. Regarding oncology the role of (18)F-fluorodeoxyglucose ((18)F-FDG) PET is proved in several clinical questions, including urooncology. Urologic cancers are associated with low or slightly significant uptake of FDG, due to their more benign behaviour. However, alternative PET tracers have been developed which show promising clinical results and hopefully, in the near future the combination of different tracers are awaited. Additionally, in the future the use of multiparametric measurements, multitracer techniques, and the multimodal PET/magnetic resonance imaging (PET/MRI) technology is going to have a crucial clinical role.

Patient satisfaction during radiation therapy. Correlates and patient suggestions.

BACKGROUND: Assessing patient satisfaction might help to detect so far unknown patient needs and could contribute to quality assurance within the health care system. We evaluated patient satisfaction and its correlates in a consecutive sample of patients undergoing external beam radiation therapy. PATIENTS AND METHODS: Patient satisfaction was evaluated within a prospective study with two validated instruments (FPZ, ZUF-8) during the first week of radiation therapy in two university-based radiation oncology departments. RESULTS: A total of 273 patients could be analyzed. Most patients were irradiated for breast or urogenital cancer. Overall patient satisfaction was high (94.9-98.8%). The most important items for patient satisfaction included the following: "skills of physicians" followed by "physician contact with patients," "care," and "information" (Tab. 2). Neither center nor disease entity correlated with global patient satisfaction. Of the patients, 46% reported that they would have preferred additional information prior to the onset of radiotherapy. Patients who sought additional information reported a lower global patient satisfaction (p < 0.001). In multiple linear regression analysis, the need for more information, male gender, and a higher level of education were significant predictors for lower global patient satisfaction (Tab. 6). CONCLUSION: During the first week of radiation therapy, patients rate patient-physician interaction and communication on treatment and disease as important factors for their satisfaction. Supplying additional information to subsets of patients prior to starting radiotherapy might help to further improve satisfaction.

Does surgery or radiation therapy impact survival for patients with extrapulmonary small cell cancers?

BACKGROUND AND OBJECTIVES: Extrapulmonary small cell carcinomas (EPSCC) are rare tumors where therapy remains poorly defined. We sought to determine the impact of surgical extirpation and radiation therapy for outcomes of EPSCC. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with EPSCC which were further categorized by site and evaluated for survival by specific treatment strategy. RESULTS: We identified 94,173 patients with small cell carcinoma of which 88,605 (94.1%) and 5,568 (5.9%) had pulmonary small cell carcinoma and EPSCC, respectively. EPSCC patients were subdivided by site with the following proportions: genitourinary (24.1%), gastrointestinal (22.1%), head and neck (7.1%), breast (4%), and miscellaneous (42.7%). Overall EPSSC and specifically gastrointestinal disease had significantly improved median, 5- and 10-year survival with surgery and/or radiation for all stages and sizes. For all EPSCCs multivariate analysis revealed age (>50), gender (female), stage (regional, distant), radiation, and surgery to be independent predictors of survival. CONCLUSIONS: Although outcomes for EPSCC remains poor, both surgery and radiation is shown to significantly improve median, 5- and 10-year survival rates. EPSCC patients who are potential candidates for surgical resection or radiation therapy may benefit from these treatments.

An ionising radiation-induced specific transcriptional signature of inflammation-associated genes in whole blood from radiotherapy patients: a pilot study.

BACKGROUND: This communication reports the identification of a new panel of transcriptional changes in inflammation-associated genes observed in response to ionising radiation received by radiotherapy patients. METHODS: Peripheral blood samples were taken with ethical approval and informed consent from a total of 20 patients undergoing external beam radiotherapy for breast, lung, gastrointestinal or genitourinary tumours. Nanostring nCounter analysis of transcriptional changes was carried out in samples prior and 24 h post-delivery of the 1st radiotherapy fraction, just prior to the 5th or 6th fraction, and just before the last fraction. RESULTS: Statistical analysis with BRB-ArrayTools, GLM MANOVA and nSolver, revealed a radiation responsive panel of genes which varied by patient group (type of cancer) and with time since exposure (as an analogue for dose received), which may be useful as a biomarker of radiation response. CONCLUSION: Further validation in a wider group of patients is ongoing, together with work towards a full understanding of patient specific responses in support of personalised approaches to radiation medicine.

LATE RADIATION TOXICITY AFTER RADICAL RADIOTHERAPY FOR GENITAL CANCER. / PIZNIa PROMENEVA TOKSYChNIST' PISLIa RADYKAL'NOÏ RADIOTERAPIÏ RAKU GENITALII.

Radiation therapy for malignant tumors of the female genital area, even with the use of modern radiotherapy equipment and dosimetric planning, causes the development of local radiation changes. An approach involving methodsof general and local exposure is used in their treatment. One of the most promising directions is the creation of optimal combinations of medicines (in the form of ointments, gels, aerosols, suppositories, etc.), which have a therapeutic effect on the inflammatory process. The article reflects the clinical course and stage of occurrence of late radiation reactions of the skin, vaginal/cervix mucosa, bladder, and intestines, as well as the features of their treatment.Literary data and own practical experience in the treatment of radiation complications are presented. Whenreviewing the topic under study, it could be concluded that the leading cause of the development of local radiationdamage is the errors in the planning and implementation of radiation therapy, when high absorbed doses thatexceed the tolerance of healthy tissues are used. Another reason for this is the poor accounting for dose distribution of ionizing radiation in tissues, the presence of concomitant diseases in patients, and the underestimation ofthe long-term effects of radiation.

Temporal Trends of Resident Experience in External Beam Radiation Therapy Cases: Analysis of ACGME Case Logs from 2007 to 2018.

PURPOSE: We sought to characterize temporal trends of radiation oncology resident-reported external beam radiation therapy (EBRT) case experience with respect to various disease sites, including trends in stereotactic radiosurgery and stereotactic body radiation therapy cases. METHODS AND MATERIALS: Summarized, deidentified case logs for graduating radiation oncology residents between 2007 and 2018 were obtained from the Accreditation Council for Graduate Medical Education national summary data report. Mean number of cumulative cases and standard deviations per graduating resident by year were evaluated. Cases were subdivided into 12 disease-site categories using the Accreditation Council for Graduate Medical Education classification. Analysis of variance was used to determine significant differences, and strength of association was evaluated using Pearson correlation. RESULTS: The number of graduating residents per year increased by 66% from 114 in 2007 to 189 in 2018 (P < .001, r = 0.88). The overall mean number of EBRT cases per graduating resident decreased by 13.2% from 521.9 in 2007 to 478.5 in 2018, with a decrease in the ratio of nonmetastatic to metastatic cases per graduating resident. There was significant variation among the disease categories analyzed; however, the largest proportionate decreases were seen in hematologic, lung, and genitourinary malignancies. Stereotactic radiosurgery volume per graduating resident increased from an average of 27.9 cases in 2007 to 50.3 in 2018 (P < .001, r = 0.96). Stereotactic body radiation therapy volume per graduating resident increased as well, from a mean of 6 cases in 2007 to 55.6 cases in 2018 (P < .001, r = 0.99). CONCLUSIONS: We report a longitudinal summary of resident-reported experience in EBRT cases. These findings have implications for future efforts to optimize residency training programs and requirements.

Combining Immunotherapy with Radiotherapy for the Treatment of Genitourinary Malignancies.

CONTEXT: Immunotherapy drugs, particularly checkpoint inhibitors, have recently been approved by the Food and Drug Administration for various malignancies. Preclinical and early clinical data show that combining these agents with radiotherapy may produce an even more potent antitumor effect in the treatment of cancer. OBJECTIVE: To describe the rationale, available data, and emerging data on the use of combined immunotherapy and radiation therapy in the setting of genitourinary (GU) malignancies. EVIDENCE ACQUISITION: We performed a search of primary studies from PubMed/Medline that included combinations of the search terms "radiation therapy," "radiotherapy," "abscopal effect," "immunotherapy," "combined," and "combination." EVIDENCE SYNTHESIS: Preclinical and clinical data support both immune-stimulating and immune-suppressing effects of radiotherapy. Preclinical and clinical studies investigating the combination of radiotherapy with immunotherapy, primarily in the setting of non-GU malignancies, have suggested efficacy and tolerability. Early randomized trials combining radiotherapy and immunotherapy have demonstrated success in lung cancer. Although a trial investigating combined immunotherapy and radiotherapy use for prostate cancer did not clearly improve survival, trials are ongoing in multiple GU malignancies to identify synergy between immunotherapy and radiotherapy. Several practical and technical questions remain about the optimal combination of radiotherapy and immunotherapy. CONCLUSIONS: Preclinical and clinical trials show that the combination of the immunotherapy and radiation therapy has the potential to provide a synergistic effect in treating cancer, including GU malignancies, although more work is needed to uncover the mechanism and determine the optimal delivery of this treatment. PATIENT SUMMARY: This paper reviews evidence that immunotherapy drugs can be given together with radiation therapy to improve outcomes in cancers of the genitourinary tract. We find promising initial results and raise important questions that need to be answered before this type of treatment can be utilized successfully.

Median effective local anesthetic doses of plain bupivacaine and ropivacaine for spinal anesthesia administered via a spinal catheter for brachytherapy of the lower abdomen.

BACKGROUND AND OBJECTIVES: Continuous spinal anesthesia via a spinal catheter allows adjusting the duration and extent of anesthesia to surgical needs, maintenance of hemodynamic stability, and good postoperative analgesia. This study was designed to determine the median effective local anesthetic dose of plain ropivacaine and bupivacaine administered intrathecally for interstitial brachytherapy of the lower abdomen using the Dixon up-and-down method. METHODS: Forty patients were randomly allocated to receive either intrathecal bupivacaine 5 mg per mL or ropivacaine 10 mg per mL via a 24-gauge spinal catheter at the L3-4 interspace. The initial dose was 10 mg of bupivacaine or 20 mg of ropivacaine; the dosing intervals were 1 mg and 2 mg, respectively. Doses for subsequent patients were determined by the response of the previous patient in that group. Successful anesthesia was defined as a loss of sensation to a cold stimulus at the T6 level and full motor blockade within 20 minutes after administration of the local anesthetic. RESULTS: The median effective local anesthetic dose for intrathecal bupivacaine was 11.2 mg (95% confidence interval [CI], 10.3-12.1) and 22.6 mg for ropivacaine (95% CI, 20.5-24.6). A relative analgesic potency ratio of 0.50 (95% CI, 0.44-0.56) was calculated between the median effective local anesthetic dose of intrathecal bupivacaine and ropivacaine. CONCLUSIONS: Bupivacaine and ropivacaine are appropriate for continuous spinal anesthesia for interstitial radiation therapy procedures of the lower abdomen. In the dose-ranges investigated, intrathecal ropivacaine is approximately half as potent as bupivacaine.

Evaluation of quality of life and psychological response in cancer patients treated with radiotherapy.

PURPOSE: The importance of the quality of life (QOL) and mental condition of patients being treated for cancer is now recognized. In this study, we evaluated QOL and mental condition in patients with cancer before and after radiotherapy. MATERIALS AND METHODS: The subjects were 170 patients who had undergone radiotherapy. The examination of QOL was performed using the quality of life questionnaire for cancer patients treated with anticancer drugs (QOL-ACD), and mental condition (anxiety and depression) was examined using the hospital anxiety and depression scale (HADS). These examinations were performed at the start of radiotherapy and immediately after radiotherapy. RESULTS: The QOL score was slightly higher in all patients after the completion of radiotherapy than before the start of radiotherapy. In the palliative radiotherapy group, QOL score was significantly improved by treatment. Anxiety and depression were improved after radiotherapy. There was a correlation between the degrees of improvement of the HADS and QOL score. CONCLUSION: We could treat cancer patients by radiotherapy without reducing their QOL, and improvement in QOL was significant in the palliative radiotherapy group. Mental condition was also improved after radiotherapy.

Dicentric Dose Estimates for Patients Undergoing Radiotherapy in the RTGene Study to Assess Blood Dosimetric Models and the New Bayesian Method for Gradient Exposure.

The RTGene study was focused on the development and validation of new transcriptional biomarkers for prediction of individual radiotherapy patient responses to ionizing radiation. In parallel, for validation purposes, this study incorporated conventional biomarkers of radiation exposure, including the dicentric assay. Peripheral blood samples were taken with ethical approval and informed consent from a total of 20 patients undergoing external beam radiotherapy for breast, lung, gastrointestinal or genitourinary tumors. For the dicentric assay, two samples were taken from each patient: prior to radiotherapy and before the final fraction. Blood samples were set up using standard methods for the dicentric assay. All the baseline samples had dicentric frequencies consistent with the expected background for the normal population. For blood taken before the final fraction, all the samples displayed distributions of aberrations, which are indicative of partial-body exposures. Whole-body and partial-body cytogenetic doses were calculated with reference to a 250-kVp X-ray calibration curve and then compared to the dose to blood derived using two newly developed blood dosimetric models. Initial comparisons indicated that the relationship between these measures of dose appear very promising, with a correlation of 0.88 (P = 0.001). A new Bayesian zero-inflated Poisson finite mixture method was applied to the dicentric data, and partial-body dose estimates showed no significant difference (P > 0.999) from those calculated by the contaminated Poisson technique. The next step will be further development and validation in a larger patient group.