Local External Beam Radiotherapy Research Articles

Natural history and treatment outcome of radiotherapy for Kimura's disease.

Kimura's disease is a rare inflammatory disease that usually appears in head and neck region. We reported natural history of the disease and treatment outcome of radiotherapy (RT) in Chiang Mai University Hospital. A retrospective review was performed for all Kimura's disease patients treated with radiotherapy at our center between 2002 and 2017. A total of 20 patients with Kimura's disease were reviewed. There were 14 men and 6 women. All patients presented with the mass in head and neck region. Eleven patients were treated with a definitive intent with RT, 9 patients were treated with RT after recurrence from other modalities. All patients were treated with local external beam RT with 2 Gy per fraction to a median total dose of 30 Gy (range 30-40). The median follow-up time was 4 years (range 1-16.5 years). One patient died from HIV opportunistic infection after 1.5 year of radiation with complete response of Kimura's disease. Most of the patients responded to radiotherapy and controlled the disease at the time of analysis. Two patients had multiple recurrences at new areas outside radiotherapy field. Skin toxicity grade 1 was the most common late side effect which was found in 8 (44%) patients. We did not find severe late toxicity or second malignancy in this patient cohort. : Good local control of Kimura's disease can be achieved, with a radiation dose of 30-40 Gy, with insignificant late toxicities. We suggest that radiotherapy should be one of the treatments of choice for Kimura's disease both in primary or recurrence setting.

Clinical outcome in metastatic prostate cancer after primary radiotherapy

PurposeTo describe a local radio-oncological treatment for patients with prostate cancer that metastasized to either the lymph nodes or distant regions.Methods and materialsWe included 133 patients with prostate cancer that displayed either distant metastases (DM) or lymph node metastases alone (NM) and were treated between 2004 and 2019. All patients underwent computed tomography and a bone scan or 18F- or prostate-specific membrane antigen-targeted positron emission tomography. Patients received local external beam radiation therapy to the prostate to achieve local control (60–81.4 Gy to the prostate, and 45–50.4 Gy to pelvic lymph nodes), with either the 3D conformal (4-field box) or volumetric modulated arc therapy technique. A urologist prescribed additional therapy.ResultsWe included 51 patients with DM and 82 patients with NM. The mean follow-up was 42 months for all patients. The groups were similar in T stage, initial prostate-specific antigen, histology, androgen deprivation therapy, age, treatment techniques, and prescribed doses, but different in lymph node inclusion and follow-up times. In the NM and DM groups, the 5‑year biochemical recurrence-free rates were 52% and 24%, respectively (p < 0.0001); the 5‑year disease-specific survival rates were 92% and 61%, respectively (p = 0.001); and the 5‑year OS rates were 77% and 48%, respectively (p = 0.01). The groups had similar acute and late gastrointestinal and genitourinary side effects, except that late genitourinary side effects occurred significantly more frequently in the NM group (p = 0.01).ConclusionsDM was associated with significantly worse outcomes than NM. The long-term survival of patients with metastatic prostate cancer was low.

Abstract 6216: Intratumoral B0112 in combination with radiotherapy synergizes to achieve CD8 T cell mediated local tumor control

Abstract Background: Radioimmunotherapy combines irradiation of tumor lesions with immunotherapy to achieve local and abscopal control of cancer. Most immunotherapy agents are given systemically, but strategies for delivering immunotherapy locally are under clinical scrutiny to maximize efficacy and avoid toxicity. Local immunotherapy by injecting various patterns of molecules shows efficacy both preclinical and clinically. BO112 is a viral mimetic based on nanoplexed double stranded RNA (poly IC) which exerts immune-mediated antitumor effects in mice and humans upon intratumoral delivery. BO112 and external beam irradiation were used to make the proof-of-concept local immunotherapy plus radiation therapy combinations. Methods: Murine transplantable tumor cells lines (TSA, MC38 and B16 ova) were used to show increased immunogenic features under irradiation as well as bilateral tumor models in which only one of the lesions could be irradiated. Flow cytometry on cell suspensions from tumor draining lymph nodes and multiplex tissue immunofluorescence were used to determine mechanims of antitumor immunity. Depletions of immune cell populations and knock out mice for IFNAAR and BAFT3 genes were used to delineate the immune system requirements for efficacy. Results: In cultures of TSA breast cancer cells the combination of irradiation and BO112 showed more prominent features of immunogenic tumor-cell death including type I interferon reléase. Injection of BO112 in the tumor lesions under radiation achieved excellent control of the treated tumors whilst modest delays in contralateral tumor progression were observed. Local effects were associated with more prominent presence of antitumor CTLs and cDC1 dendritic cells in the tumor and regional lymph nodes. Importantly, local irradiation plus BO112 in a tumor lesion enhanced the therapeutic effect of radiotherapy on distant uninjected tumor lesion. Conclusions: This study demonstrates that local BO112 immunotherapy and external beam radiation therapy can exert synergies to achieve local tumor control. This beneficial effect can be extended to non-injected lesions as long as they are also irradiated, suggesting strategies to treat oligometastatic patients with lesions susceptible to radiotherapy and at least one of them accessible for BO112 repeated intratumoral injections. Citation Format: Maria.E. Rodriguez-Ruiz, Irantzu serrano, Eneko Garate, Inmaculada Rodriguez, maite alvarez, Carmen Molina, Miguel Fernandez de Sanmamed, Leire Arbea, Marta Moreno, Marisol Quintero, Ignacio Melero. Intratumoral B0112 in combination with radiotherapy synergizes to achieve CD8 T cell mediated local tumor control [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6216.

Survival rates with external beam radiation therapy in newly diagnosed elderly metastatic prostate cancer patients.

The survival benefit of primary external beam radiation therapy (EBRT) has never been formally tested in elderly men who were newly diagnosed with metastatic prostate cancer (mPCa). We hypothesized that elderly patients may not benefit of EBRT to the extent as younger newly diagnosed mPCa patients, due to shorter life expectancy. We relied on Surveillance, Epidemiology and End Results (2004-2016) to identify elderly newly diagnosed mPCa patients, aged >75 years. Kaplan-Meier, univariable and multivariable Cox regression models, as well as Competing Risks Regression models tested the effect of EBRT versus no EBRT on overall mortality (OM) and cancer-specific mortality (CSM). Of 6556 patients, 1105 received EBRT (16.9%). M1b stage was predominant in both EBRT (n = 823; 74.5%) and no EBRT (n = 3908; 71.7%, p = 0.06) groups, followed by M1c (n = 211; 19.1% vs. n = 1042; 19.1%, p = 1) and M1a (n = 29; 2.6% vs. n = 268; 4.9%, p < 0.01). Median overall survival (OS) was 23 months for EBRT and 23 months for no EBRT (hazard ratio [HR]: 0.97, p = 0.6). Similarly, median cancer-specific survival (CSS) was 29 months for EBRT versus 30 months for no EBRT (HR: 1.04, p = 0.4). After additional multivariable adjustment, EBRT was not associated with lower OM or lower CSM in the entire cohort, as well as after stratification for M1b and M1c substages. In elderly men who were newly diagnosed with mPCa, EBRT does not affect OS or CSS. In consequence, our findings question the added value of local EBRT in elderly newly diagnosed mPCa patients.

Аденокарцинома сальной железы века

Sebaceous carcinoma belongs to rare malignant tumors of the eyelids, is characterized by a variety of clinical manifestations and is often disguised as other tumors or inflammatory diseases of the eyelids. The purpose of the work is to analyze the clinical picture and features of the course of sebaceous carcinoma. Material and methods. From January 2015 to December 2020, 6 patients were diagnosed with cancer of the sebaceous gland (5 patients with adenocarcinoma of the meibomian glands, 1 with adenocarcinoma of the Zeiss sebaceous glands). 4 were women and 2 were men aged from 59 to 89 years. Results. From the moment the first symptoms appeared to adequate treatment, 6-12 months passed. According to the 8th revision of the T-classification of malignant tumors of the AJCC eyelids, two patients had T2b, three had T3b, and one patient had T3c stage. A painless thickening of the eyelid cartilage and the eyelid margin was accompanied by the growth of yellowish dense masses on the conjunctiva in two women; the tumor spread to the eyelid skin in one patient. By the time the primary tumor was diagnosed, none of the patients had metastases to regional lymph nodes and hematogenous metastases. Wide excision of the tumor with simultaneous plastic surgery of the eyelid was performed in 4 patients. After excisional biopsy, 3 patients underwent local external beam radiation therapy to the area of the affected eyelid (Total dose 60 Gy.). Orbital exenteration was performed in two patients. The observation period for the patients: 3 months – 49 months. One patient died of a cause unrelated to the tumor. One patient died of metastases of Zeiss glands adenocarcinoma. Relapse of the tumor developed and metastasis to the preauricular lymph node appeared in one patient. Conclusion. Diagnosis of the sebaceous gland cancer of the eyelids is difficult, it is detected late. Ki67 does not depend on the size of the tumor, however, the large size of the tumor is an unfavorable factor in the prognosis of the disease. All patients with cancer of the sebaceous gland after treatment need to be followed up for at least 5 years with whole body PET/CT once a year. Key words: sebaceous carcinoma of the eyelids, adenocarcinoma of the meibomian glands, adenocarcinoma of the Zeiss sebaceous glands.

Long-term follow-up comparing salvage radiation therapy and androgen-deprivation therapy for biochemical recurrence after radical prostatectomy

The salvage treatments for biochemical recurrence (BCR) include local external beam radiation therapy (RT) and systemic androgen-deprivation therapy (ADT). We reviewed patients who underwent radical prostatectomy (RP) and developed BCR at three institutions. After excluding patients whose nadir prostate-specific antigen (PSA) was higher than 0.2ng/mL, those who received neoadjuvant/adjuvant therapy, and those whose BCR was not treated until their PSA exceeded 4.0ng/mL, the remaining 335 patients comprised the cohort of this study. Salvage RT and ADT were performed for 154 and 181 patients, respectively. After the failure of salvage RT, all patients received subsequent ADT. The starting point of this study was the timing of BCR and the endpoint was the development of castration-resistant prostate cancer (CRPC). During the mean follow-up period of 8.5years after BCR, CRPC was observed in 13 patients administered RT and 24 patients administered ADT. Kaplan-Meier curves demonstrated no significant difference in CRPC-free survival between the RT and ADT groups (10-year CRPC-free survival 89.9 vs. 86.3%, p = 0.199). On the other hand, we found a significant difference in CRPC-free survival between the RT and ADT groups in 50 high-risk patients with two risk factors of Grade Group ≥ 4 and PSA-doubling time < 6months (10-year CRPC-free survival 73.4 vs. 40.3%, p = 0.040). This study revealed that salvage RT increases the CRPC-free survival rate compared with salvage ADT in high-risk patients with Grade Group ≥ 4 and PSA-doubling time < 6months.

Choice of treatment options for metastatic hormone-sensitive prostate cancer

The arsenal of available treatments and treatments for metastatic hormone-sensitive prostate cancer (mHRPC) has increased significantly over the past 5 years. Although androgen-preferential therapy (ADT) remains the mainstay of treatment, the addition of docetaxel, abiraterone, enzalutamide, apalutamide, or local external beam radiation therapy improves the outcome of patients with mHRPC and becomes the standard of care. Choosing a therapy to improve treatment outcomes for patients with mHRPC is becoming increasingly challenging as there are different options for this stage of the disease. This article provides an overview of clinical trials that included ADT in combination with chemotherapy, new hormonal therapy, and radiation therapy. We will also consider recent advances in the choice of treatment for men diagnosed with mHPCR and the impact of previous therapy on the subsequent biology of the disease. Options include chemohormone therapy, androgen receptor (AR) targeted therapy in addition to ADT or, less commonly, ADT alone. The choice of treatment should be based on a consideration of the clinical characteristics and characteristics of the disease, as well as taking into account the patient’s preferences, territorial constraints and financial resources.

Acute Palliation of Intrathoracic Symptoms: No Improvement with Dose-Escalated Hypofractionated External Beam Radiotherapy

Primary or metastatic malignant disease is a known cause of intrathoracic symptoms in oncologic patients and, frequently, obstruction of the bronchial tree may lead to dyspnea and/or hemoptysis. Local external beam radiotherapy (EBRT) can be an option to palliate such symptoms, even in spite of its low efficiency rate. We hypothesized that dose escalation could be safely delivered and further improve symptoms relief rates in patients who did not respond to an initial course of hypofractionated EBRT. A prospective, single arm, uni-institutional study was conducted, and eligible patients were offered a course of local hypofractionated EBRT, with 2 weekly fractions of 8 Gy, and an additional fraction of 8 Gy, if there were no symptoms improvement, one week apart. Study primary endpoint was to assess the rate of acute palliation of intrathoracic symptoms (hemoptysis resolution and/or dyspnea improvement, measured by the Modified Medical Research Council [mMRC] Dyspnea Scale). Secondary endpoints included the assessment of any possible treatment side-effects and late symptom improvement. Patients were clinically evaluated before every EBRT session, and if there was no clinical improvement after the second and immediately before the third session, the patient was recommend to continue the proposed treatment, to a total dose of 24 Gy. After that, follow-up was performed on a regular basis, to evaluate any possible treatment sub-acute or late side-effects or symptom improvement. After ERB approval, on September 2017, 8 eligible patients (5 males and 3 females) were initially enrolled, until interim analyses, on August 2018, when investigators decided to close accrual due to poor response to the treatment protocol. Median age of the patients was 51,5 years (39 - 72), all of them with metastatic disease and 5 of them (62,5 %) with a non-pulmonary primary malignancy. All of the patients presented with dyspnea, and 2 (25 %) of them also with hemoptysis, and, according to mMRC Dyspnea Scale, 6 patients (75 %) had a grade 3 or higher dyspnea symptom. Overall, 5 of the patients demanded a third session, but one patient died from disease progression before the second and one before the third session. After the completion of the treatment protocol, 4 patients had any acute dyspnea improvement and both the patients who presented with hemoptysis had symptom resolution (one after the second session, and therefore was not submitted to the third one). However, none evolved with significant dyspnea palliation after the third session. Except for one patient, that was still alive 12 months after the EBRT, all the other patients died within 4 months after the completion of the treatment. Two out of 3 patients who completed the 3 sessions also developed symptomatic actinic esophagitis. Dose-escalated hypofractionated EBRT didn’t provide acute palliation of intrathoracic symptoms in this small cohort of patients, despite any dyspnea improvement in 5 out of 8 patients.

SUN-378 Adrenocortical Carcinoma Diagnosed During Evaluation of an Incidentally Discovered Adrenal Mass

Background. Adrenocortical carcinoma (ACC) is a rare neoplasm with an estimated incidence of 0.5-2.0 per million per year. Most patients present with symptoms or signs of hormone excess or complaints related to tumor mass effect. We present a case of ACC discovered incidentally on computed tomography (CT) imaging of the abdomen. Case. A 59-year-old female presented to the emergency department (ED) after falling in her shower. She felt light headed before the fall, but she denied loss of consciousness or confusion after the event. The patient was noted to be hypertensive (185/105 mm Hg) and hypokalemic (2.6 mM, 3.6-5.1). A contrast enhanced abdominal CT scan revealed a 9.1 cm heterogeneous left adrenal mass. Plasma metanephrine and normetanephrine levels were unremarkable. Morning cortisol failed to suppress during a 1 mg overnight dexamethasone suppression test (10.1 μg/dL, < 1.8), and plasma midnight cortisol was unequivocally elevated at 24.3 μg/dL (< 7.5). ACTH (5 pg/mL, 6-58) and DHEA (0.159 ng/mL, 0.630-4.700) levels at 8 AM were both low. Postsurgical histopathology was notable for high grade mitoses (> 20/50 high powered fields), capsular invasion into peri-adrenal adipose tissue, and lymphovascular invasion, though surgical margins were uninvolved by tumor. No evidence of locoregional or distant metastases was observed on tumor staging, leading to a diagnosis of stage III ACC (T3N0M0). The patient elected treatment with local external beam radiation but declined mitotane. Secondary adrenal insufficiency is managed with hydrocortisone. Discussion. This patient’s case illustrates the female predominance (1.5-2.5:1) and typical time of diagnosis (fifth-to-sixth decade) reported in adult cases of ACC. It is unusual because only 20-30% of cases are diagnosed incidentally during imaging for an unrelated medical problem, and ACC accounts for only about 2-5% of incidentally diagnosed adrenal masses. The size (> 4 cm) and heterogeneity of the patient’s tumor were radiographic features indicating ACC, and the finding of adrenal hypercortisolemia is consistent with the high prevalence (45-70%) of metabolically active tumors that predominantly secrete cortisol. Hypertension and hypokalemia likely reflect saturation of renal 11-β-hydroxysteroid dehydrogenase with excess cortisol, though the patient lacked the features of rapidly progressive Cushing’s syndrome described in many cases of cortisol secreting ACC. Most cases of ACC are stage II or higher at initial diagnosis, and five-year survival for advanced stage ACC is only 10-25%. Disease stage and completeness of resection are the most important factors that influence prognosis, though high mitotic rate and hypercortisolemia in this patient’s case are negative prognostic factors. Adjuvant mitotane appears to improve recurrence-free survival, and radiation reduces the rate of local tumor recurrence.

Surgery Versus Radiation Treatment for High-Grade Neuroendocrine Cancer of Uterine Cervix: A Surveillance Epidemiology and End Results Database Analysis.

The objective of this study was to assess treatment and other factors impacting survival in cervical high-grade neuroendocrine carcinoma (HGNEC). We identified patients with cervical HGNECs diagnosed during 1988 to 2012 in the Surveillance Epidemiology and End Results database. We determined overall survival by International Federation of Gynecology and Obstetrics stages and by local treatment modalities, that is, radical surgery versus external beam radiation treatment (EBRT) plus brachytherapy using Kaplan-Meier analysis with log-rank test. We also determined factors of age, stage, and treatment modality impacting survival using proportional hazard analysis. We identified 832 cases of cervical HGNECs in the database. After excluding cases with incomplete stage data, the International Federation of Gynecology and Obstetrics stages I to IV distributions were 196 (28.0%), 69 (9.9%), 175 (25.0%), and 260 patients (37.1%), respectively. Radical surgery and primary radiotherapy yielded similar 5-year overall survival for stages I (61% vs 53%, P = 0.27), II (48% vs 28%, P = 0.308), and III (33% vs 28%, P = 0.408) patients. External beam radiation treatment plus brachytherapy did not yield superior survival than EBRT alone in stage I (48% vs 49%, P = 0.799), II (37% vs 20%, P = 0.112), or III (25% vs 32%, P = 0.636) patients. Age (P = 0.004) and stage (stage II: hazard ratio [HR], 1.78, P = 0.013; stage III: HR, 2.42; P < 0.001) were independent factors impacting survival but not local treatment modality (EBRT: HR, 1.30, P = 0.17; EBRT plus brachytherapy: HR, 1.16; P = 0.417). Patients with cervical HGNECs had poor prognosis. Primary treatment by radical surgery or external beam radiotherapy with or without brachytherapy yielded equally poor survival.

486P Samarium-153 adjuvant to palliative local radiotherapy for bone metastases: Efficacy and complications

Background This study was undertaken for evaluation of the efficacy and complications of the bone-seeking radiopharmaceutical Samarium-153 (153Sm- EDTMP) added to local external beam radiotherapy (EBRT) for palliation of patients with metastatic bone pain. Methods Patients with multiple bone metastases and an estimated life expectancy of more than 3 months were eligible for this study, provided that they had a dominant localized pain for which palliative EBRT with local fields had been planned. Treatment was intravenous injection of 1.5 mCi (56 MBq)/kg of 153Sm-EDTMP, and local radiotherapy with 30 Gy in 10 fractions. Pain scoring was performed by the Farsi (Persian) version of Brief Pain Inventory (BPI), and response was categorized according to the International Consensus on Bone Metastases guidelines. Results Twenty-six patients (10 male, 16 female,) aged 30-80 years (mean 55 years) were enrolled in the study. Primary cancers were 15 breast, 7 prostate, and 4 others. Of the enrolled patients, 23 received the full treatment and were available for pain response evaluation. In these patients, overall response was 90% and there was 10% no response. 30% of the patients had a significant response with their pain score reducing to more than half. One patient (4.3%) experienced grade 3 leucopenia, and 1 patient grade 3 thrombocytopenia. All other patients experienced grade 0-2 of bone marrow toxicity. Conclusions 153Sm-EDTMP adjuvant to local radiotherapy resulted in higher overall response compared to the results of our studies on EBRT alone and Samarium alone in similar populations of patients, and to the results in literature. Samarium did not significantly add to the complications of radiotherapy alone. Clinical trial indentification 92-03-51-24776 Tehran University of Medical Sciences. Legal entity responsible for the study Radiation Oncology Research Center, Cancer Institute, Tehran University of Medical Sciences Funding Tehran University of Medical Sciences Disclosure All authors have declared no conflicts of interest.

Radiation therapy for the treatment of skin Kaposi sarcoma.

Kaposi sarcoma (KS) lesions are purplish, reddish blue or dark brown/black macules, plaques or nodules which involve the skin and occasionally internal organs. Most patients with KS have a long indolent chronic course. A retrospective review was undertaken for all KS skin patients treated with radiotherapy at a tertiary cancer centre from Jan. 2, 1999 to Dec. 31, 2014 (inclusive). A total of 47 patients with KS (43 classical, 0 African, 1 iatrogenic, 3 AIDS related) were seen in the multidisciplinary clinic. Out of this group, 17 patients (5 females and 12 males, 14 classical, 0 African, 0 iatrogenic, 3 AIDS related) with 97 KS skin sites were treated with local external beam radiotherapy. An additional 18 skin sites were treated with repeat radiotherapy. The radiotherapy dose ranged from 6 Gy in 1 fraction to 30 Gy in 10 fractions with the most common dose fractionation scheme being 8 Gy in 1 fraction or 20 Gy in 5 daily fractions. For the previously untreated KS sites, 87% responded to radiation [30% complete response (CR) and 57% partial response (PR)]. Thirteen percent of KS sites treated with radiation progressed. For the skin sites which were treated with repeat radiotherapy, 0% showed CRs, 50% PRs and 50% had continued progression. The majority of KS skin lesions (87%) responded to radiotherapy. Patients experience minimal side effects from the palliative radiation regimens used. KS skin lesions which progress despite radiation are unlikely to show CR with repeat radiotherapy. In our experience 50% of skin KS will have partial regression with repeat radiotherapy and 50% will have continued progression.

Breast cancer presenting with intramedullary cervical spinal cord metastasis

A 45-year-old female patient was admitted to our hospital with complaints of weakness in her legs. There was no disturbance in sphincter function. Neurologic examination revealed generalized weakness and numbness in all four limbs. Examination of cranial nerves and tendon reflexes revealed normal functioning. Magnetic resonance imaging of the cervical spine demonstrated a 3 cm×0.9 cm×1.1 cmmass between the inferior two thirds of C2 and superior third of C3 (Figure). The mass was isointense on T1-weighted images, hyperintense on T2-weighted images, and homogeneously enhancing on post-contrast T1-weighted images. Sagittal T2-weighted images showed a pencil-shaped hyperintensity extending proximal to the lesion (Figure). The features were typical for intramedullary spinal cord metastasis (ISCM) [1]. An Ffluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) scan showed a left breast lesion and multiple liver lesions. The patient underwent biopsy of the left breast mass and a liver mass. The breast mass was found to be a poorly differentiated, estrogen/progesterone (ER/ PR)-negative infiltrating ductal carcinoma, and an enlarged 1.6-cm left axillary lymph node biopsy revealed metastatic adenocarcinoma. The liver mass biopsy was reported to be an ER/PR-negative adenocarcinoma, consistent with metastatic breast cancer. The patient was started on dexamethasone, chemotherapy, and local external beam radiation therapy to the cervical spinal cord. After completion of the radiotherapy, there was improvement in the weakness and numbness of the extremities. The patient remained stable neurologically for 2 months after the diagnosis of breast cancer until death due to the liver metastases. Breast cancers can present with symptoms of the spinal cord metastasis. Intramedullary spinal cord metastasis of breast cancer is an extremely rare but severe condition that can cause neurologic deficits. Metastatic breast cancer should be considered when the typical features of ISCM are seen on spinal magnetic resonance imaging.

Localized External Beam Radiation Therapy (EBRT) to the Pelvis Induces Systemic IL-1Beta and TNF-Alpha Production: Role of the TNF-Alpha Signaling in EBRT-Induced Fatigue.

Prostate cancer patients undergoing localized external beam radiation therapy (EBRT) can experience a progressive increase in fatigue, which can affect physical functioning and quality of life. The purpose of this study was to develop a mouse EBRT prostate cancer treatment model with which to determine the role of pro-inflammatory cytokines in the genesis of EBRT-related fatigue. We assessed voluntary wheel-running activity (VWRA) as a proxy for fatigue, food intake and body weight in male C57BL/6 mice undergoing EBRT to the pelvis. In the first experiment, anesthetized male C57BL/6 mice underwent fractionated EBRT to the pelvis for a total dose of 68.2 Gy, thereby mimicking a clinically relevant therapeutic dose and frequency. The day after the last treatment, levels of IL-1β and TNF-α in plasma along with mRNA levels in liver, colon and whole brain were measured. EBRT-induced fatigue resulted in reduced body weight, diminished food intake, and increased plasma and tissue levels of IL-1β and TNF-α. In a follow-up experiment, we used TNF-α-deficient mice to further delineate the role of TNF-α signaling in EBRT-induced sickness behavior. EBRT-induced changes in fatigue, food intake and body weight were no different between TNF-α deficient mice and their wild-type counterparts. Taken together our data demonstrate that a clinically relevant localized irradiation of the pelvis induces a systemic IL-1β and TNF-α response and sickness behavior in mice, but the TNF-α signaling pathway alone does not independently mediate these effects.

Diagnostic and therapeutic challenges of EBV-positive mucocutaneous ulcer: a case report and systematic review of the literature

BackgroundEpstein–Barr virus-positive mucocutaneous ulcer (EBVMCU) is a recently recognized B cell lymphoproliferative disorder that is driven by latent EBV infection and causes discrete ulcerations in the oropharynx, gastrointestinal tract, and skin. Local attenuation of immunosurveillance associated with iatrogenic immunosuppressant use, primary immunodeficiency, or age-associated immunosenescence has been implicated as a predisposing factor. This disorder is likely under reported, as it was only first defined in 2010 and shares histological features with other B-cell proliferative neoplasms. The first case series that described EBVMCU suggested that EBVMCU is generally self-limited and is likely to resolve without treatment. Since that publication, additional cases have been reported that describe a more heterogeneous clinical course, often requiring aggressive therapy. We now systematically review all published cases of EBVMCU and detail a case of aggressive and progressive EBVMCU, including diagnostic and management challenges, as well as successful treatment with radiation therapy.Case presentationA forty-nine year old woman presented with painful and debilitating multifocal oral EBVMCU that initially responded to four weekly doses of rituximab. Her disease relapsed within 3 months and continued to progress and cause significant morbidity. She was successfully treated with local external beam radiation therapy of 30 Gy in 15 fractions, with duration of response of at least 6 months.ConclusionsWe suggest that although many patients with EBVMCU experience a self-limited course, for others EBVMCU can be a debilitating, persistent disorder that requires aggressive therapy to prevent disease progression. CD20- and CD30-directed antibody therapy, local radiation therapy, local surgical excision, systemic chemotherapy, and a combination of these therapies have all been successfully used to treat EBVMCU with high rates of durable clinical remission. As EBVMCU is not currently included in the 2008 WHO classification of lymphoproliferative disorders and no evidence-based guidelines or expert opinions have been proposed to guide therapy, this case report and systematic review provides a foundation on which to guide therapeutic decisions.

Genomic Profile of Fatigued Men Receiving Localized Radiation Therapy.

The purpose of this study was to explore gene expression changes in fatigued men with nonmetastatic prostate cancer receiving localized external beam radiation therapy (EBRT). Fatigue was measured in 40 men with prostate cancer (20 receiving EBRT and 20 controls on active surveillance) using the Functional Assessment of Cancer Therapy-Fatigue (FACT-F). EBRT subjects were followed from baseline to midpoint and end point of EBRT, while controls were seen at one time point. EBRT subjects were categorized into high- and low-fatigue groups based on change in FACT-F scores from baseline to EBRT completion. Full genome microarray was performed from peripheral leukocyte RNA to determine gene expression changes related to fatigue phenotypes. Real-time polymerase chain reaction and enzyme-linked immunosorbent assay confirmed the most differentially expressed gene in the microarray experiment. At baseline, mean FACT-F scores were not different between EBRT subjects (44.3 ± 7.16) and controls (46.7 ± 4.32, p = .24). Fatigue scores of EBRT subjects decreased at treatment midpoint (38.6 ± 9.17, p = .01) and completion (37.6 ± 9.9, p = .06), indicating worsening fatigue. Differential expression of 42 genes was observed between fatigue groups when EBRT time points were controlled. Membrane-spanning four domains, subfamily A, member (MS4A1) was the most differentially expressed gene and was associated with fatigue at treatment end point (r = -.46, p = .04). Fatigue intensification was associated with MS4A1 downregulation, suggesting that fatigue during EBRT may be related to impairment in B-cell immune response. The 42 differentially expressed fatigue-related genes are associated with glutathione biosynthesis, γ-glutamyl cycle, and antigen presentation pathways.

Epithelial myoepithelial carcinoma of the lower alveolus

Epithelial-myoepithelial carcinoma (EMC) is a biphasic tumor and classified as a low-grade tumor of the salivary glands. EMC commonly occurs in the parotids with a reported incidence of around 1% out of all neoplasms of the salivary glands and it is a rare tumor of the minor salivary glands in the oral cavity, especially on the lower alveolus. A 48-year-old male patient presented with a rapidly progressive ulcer-infiltrative growth on the lower alveolus with involvement of the overlying cheek skin in a short span of period. We describe here a case of locally advanced EMC of the lower alveolus, its diagnosis by histopathological examination and immunohistochemical staining, and management by surgery and local external beam radiotherapy (EBRT). In our limited experience in the treatment of EMC on the lower alveolus, wide local excision of the tumor, followed by EBRT had resulted in a good therapeutic outcome at the 3 years posttreatment follow-up. In conclusion, EMC of the lower alveolar mucosa is extremely rare, and patients should also be advised close follow-up for the detection of loco-regional recurrences after treatment.

Management of bone metastases

The skeleton is the most common site to be affected by advanced breast, prostatic, lung, kidney, thyroid and other solid tumors (in addition to myeloma multiplex). Bone metastases cause significant morbidity with nearly always fatal outcome. Over 600 000 new patients diagnosed in the developed countries yearly. On average every 4-6 months patients suffer from series of severe skeletal complications such as pathologic fractures, spinal cord compression, hypercalcemic events, etc., besides the permanent pain. Local external beam radiotherapy, systemic radioisotope-, endocrine-, and chemotherapy, oral and i.v. bisphosphonates and recently s.c. denosumab are the mainstays of treatment, in addition to pain-killers and other usual "classical" interventions. The modern treatments singificantly reduce the probability of skeletal complications and improve the patients' quality of life and, sometimes, they extend the survival as well. The authors briefly summarize the available treatment options.

Myeloma appearance after local external beam radiotherapy jet: Is it a new entity?

Multiple myeloma, also known as Kahler's disease, is a cancer of plasma cells that abnormally accumulate in bone marrow. Radiation therapy may be indicated in multiple myeloma to relieve pain, alleviate spinal cord compression or reduce tumor mass. We report the case of a patient presenting a multiple myeloma, treated with radiation therapy for a spinal cord compression, who developed, eleven months later, an in-field subcutaneous relapse. We called this phenomenon myeloma appearance after local external beam radiotherapy jet (MAALEJ). A review of literature was performed trying to explain this uncommon relapse feature.

A Comparison of the Analgesic Effect and Toxicity of 153sm Radioisotope Treatment in Monotherapy and Combined Therapy Including Local External Beam Radiation Therapy (EBRT) Among Metastatic Castrate Resistance Prostate Cancer (MCRPC) Patients With Painful Bone Metastases

PCSM at 10 years was 4% for T3aN0M0, 11% for T3bN0M0, 9% for T4N0M0 and 20% for TanyN1M0 (p < 0.001). To examine the influence of grade on outcomes, we compared, grade I, grade II and grade III in the above groups (See Table). Conclusions: Stage IV prostate cancer is a diverse group with PCSM in various subgroups ranging from 17% to 69% at 10 years. Considering the favorable outcomes of those with T4 or N1 M0 CAP relative to M1 disease, we propose a new stage IIIB in which T4 or N1 M0 CAP should be reclassified, and patients offered curative intent therapy whenever possible. Author Disclosure: M.E. Shukla: None. C. Reddy: None. C. Yu: None. M. Abdel-Wahab: None. K. Stephans: None. R. Tendulkar: None.