Meta-Analysis of Quality of Life in Cancer Patients Treated With Immune Checkpoint Inhibitors.

BACKGROUND: Trials of immune checkpoint inhibitors (ICIs) have published patient-reported quality of life (QOL), but the size and heterogeneity of this literature can make patient education difficult. This meta-analysis aimed to describe change in QOL and symptomatology in patients receiving ICIs for cancer. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, databases were searched through November 2019 for articles or abstracts of prospective, original studies reporting longitudinal QOL in adult cancer patients treated with ICIs. The prespecified primary outcomes were change in global QOL among patients treated with ICIs and difference in change since baseline in global QOL between patients treated with ICI vs non-ICI active treatment. Secondary outcomes included physical functioning and symptomatology. All statistical tests were 2-sided. RESULTS: Of 20 323 publications, 26 met inclusion criteria. Global QOL did not change over time in patients treated with ICIs (k = 26, n = 6974; P = .19). Larger improvements in global QOL was observed in patients receiving ICI vs non-ICI regimens (k = 16, ICI: n = 3588; non-ICI: n = 2948; P < .001). Physical functioning did not change in patients treated with ICIs (k = 14, n = 3169; P = .47); there were no differences in mean change between ICI vs non-ICI regimens (k = 11, n = 4630; P = .94). Regarding symptoms, appetite loss, insomnia, and pain severity decreased, but dyspnea severity increased in patients treated with ICIs (k = 14, n = 3243-3499; P < .001). Insomnia severity was higher in patients treated with ICIs than non-ICI regimens (k = 11, n = 4791; P < .001). CONCLUSIONS: This study is among the first to quantitatively summarize QOL in patients treated with ICIs. Findings suggest ICI recipients report no change in global QOL and higher QOL than patients treated with non-ICI regimens.

A phase IB clinical trial of 15 Gy HDR brachytherapy followed by hypofractionated/SBRT in the management of intermediate-risk prostate cancer.

PURPOSE: High dose-rate (HDR) brachytherapy is commonly administered as a boost to external beam radiation therapy (EBRT). Our purpose was to compare toxicity with increasingly hypofractionated EBRT in combination with a single 15 Gy HDR boost for men with intermediate-risk prostate cancer. METHODS AND MATERIALS: Forty-two men were enrolled on this phase IB clinical trial to one of three EBRT dose cohorts: 10 fractions, seven fractions, or five fractions. Patients were followed prospectively for safety, efficacy, and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition. RESULTS: With a median follow up of 36 months, the biochemical disease-free survival was 95.5%. One man developed metastatic disease at 5 years. There was no significant minimally important difference in EPIC PRO for either urinary, bowel, or sexual domains. There was one acute Grade 3 GI and GU toxicity, but no late Grade 3 GU or GI toxicities. CONCLUSION: Fifteen gray HDR brachytherapy followed by a five fraction SBRT approach results in high disease control rates and low toxicity similar to previously reported HDR protocols with significant improvement in patient convenience and resource savings. While mature results with longer follow up are awaited, this treatment approach may be considered a safe and effective option for men with intermediate-risk disease.

Treatment patterns and disease outcomes for pediatric patients with refractory or recurrent Hodgkin lymphoma treated with curative-intent salvage radiotherapy.

BACKGROUND AND PURPOSE: The use of radiotherapy (RT) for pediatric patients with Hodgkin lymphoma (HL) experiencing disease progression or recurrence (15%) is controversial. We report treatment patterns and outcomes for pediatric patients with refractory/recurrent HL (rrHL) treated with curative-intent RT. MATERIALS AND METHODS: Forty-six patients with rrHL treated with salvage RT at our institution were identified. All received risk-adapted, response-based frontline therapy and were retrieved with cytoreductive regimens followed by RT to failure sites, with or without autologous hematopoietic cell transplantation (AHCT). Cumulative incidence (CIN) of local failure (LF) and survival were estimated after salvage RT and regression models determined predictors of LF after salvage RT. RESULTS: RT was administered as part of frontline therapy in 70% of patients, omitted for early response assessment in 13%, or deferred for primary progression in 17%. AHCT was omitted in 20% of patients. Median initial and salvage dose/site were 25.5 Gy and 30.6 Gy, respectively. Eight patients experienced progression. Two died without progression (median follow-up from salvage RT = 3.8 years). The 5-year CIN of LF after salvage RT was 17.7% (95% confidence interval [CI], 8.2-30.2%). The 5-year freedom from subsequent treatment failure and overall survival (OS) was 80.1% (95% CI, 69.2-92.6%) and 88.5% (95% CI, 79.5-98.6%), respectively. Inadequate response to salvage systemic therapy (p = 0.048) and male sex (p = 0.049) were significantly associated with LF after salvage RT. CONCLUSION: rrHL is responsive to salvage RT, with low LF rates after moderate doses. OS is excellent, despite refractory disease. Initial salvage therapy response predicts subsequent LF.

Treatment recommendations for elderly patients with newly diagnosed glioblastoma lack worldwide consensus.

BACKGROUND: Glioblastoma predominantly occurs in the 6th and 7th decades of life. The optimal treatment paradigm for elderly patients is not well established. We sampled current worldwide management strategies for elderly patients with newly diagnosed glioblastoma. METHODS: A web-based survey was developed and distributed to 168 radiation oncologists, neuro-oncologists and neurosurgeons identified through the United Council for Neurologic Subspecialties and the CNS committees for North American, European and Asian Organizations. Questions addressed treatment recommendations in order to determine whether management consensus exists in this patient subset. RESULTS: There were 68 (40%) respondents. Across respondents, the most important factors directing treatment were KPS (94%) and MGMT methylation status (71%). Only 37% of respondents strictly factor in age when making treatment recommendations with 59% defining elderly as greater than 70 years-old. The most common treatment recommendations for MGMT-methylated elderly patients with KPS > 70 were as follows: standard chemoRT (49%), short course chemoRT (39%), and temozolomide alone (30%). The most common treatment recommendations for MGMT-unmethylated patients with KPS > 70 were as follows: short course RT alone (51%), standard chemoRT (38%), and short course chemoRT (28%). Treatment recommendations for patients with KPS < 50 were short course RT alone (40%), best supportive care (57%), or TMZ alone (17%). Individuals practicing in North America were significantly more likely to recommend standard chemoradiation for patients compared to their European counterparts. CONCLUSION: Worldwide treatment recommendations for elderly patients with newly diagnosed GBM vary widely. Further randomized studies are needed to elucidate the optimal treatment strategy for this subset of patients.

Clinical Integration of Digital Solutions in Health Care: An Overview of the Current Landscape of Digital Technologies in Cancer Care.

Digital health constitutes a merger of both software and hardware technology with health care delivery and management, and encompasses a number of domains, from wearable devices to artificial intelligence, each associated with widely disparate interaction and data collection models. In this review, we focus on the landscape of the current integration of digital health technology in cancer care by subdividing digital health technologies into the following sections: connected devices, digital patient information collection, telehealth, and digital assistants. In these sections, we give an overview of the potential clinical impact of such technologies as they pertain to key domains, including patient education, patient outcomes, quality of life, and health care value. We performed a search of PubMed ( www.ncbi.nlm.nih.gov/pubmed ) and www.ClinicalTrials.gov for numerous terms related to digital health technologies, including digital health, connected devices, smart devices, wearables, activity trackers, connected sensors, remote monitoring, electronic surveys, electronic patient-reported outcomes, telehealth, telemedicine, artificial intelligence, chatbot, and digital assistants. The terms health care and cancer were appended to the previously mentioned terms to filter results for cancer-specific applications. From these results, studies were included that exemplified use of the various domains of digital health technologies in oncologic care. Digital health encompasses the integration of a vast array of technologies with health care, each associated with varied methods of data collection and information flow. Integration of these technologies into clinical practice has seen applications throughout the spectrum of care, including cancer screening, on-treatment patient management, acute post-treatment follow-up, and survivorship. Implementation of these systems may serve to reduce costs and workflow inefficiencies, as well as to improve overall health care value, patient outcomes, and quality of life.

Sleep disturbance in men receiving androgen deprivation therapy for prostate cancer: The role of hot flashes and nocturia.

BACKGROUND: Patients with prostate cancer receiving androgen deprivation therapy (ADT) are at risk of sleep disturbance; however, to the authors' knowledge, the mechanisms by which ADT may affect sleep are not well understood. The current study compared objective and subjective sleep disturbance in ADT recipients and controls and examined whether sleep disturbance in ADT recipients is attributable to the influence of ADT on hot flashes and nocturia. METHODS: Patients with prostate cancer were assessed before or within 1 month after the initiation of ADT as well as 6 months and 12 months later (78 patients). Patients with prostate cancer were treated with prostatectomy only (99 patients) and men with no history of cancer (108 men) were assessed at similar intervals. Participants self-reported their sleep disturbance (Insomnia Severity Index) and interference from hot flashes (Hot Flash Related Daily Interference Scale). One hundred participants also wore actigraphs for 3 days at the 6-month assessment to measure objective sleep disturbance and reported their nocturia frequency. RESULTS: ADT recipients reported worse sleep disturbance, higher rates of clinically significant sleep disturbance, and greater hot flash interference than controls (Ps≤.03). In cross-sectional analyses among those with actigraphy data, ADT recipients had greater objective sleep disturbance and more episodes of nocturia (Ps<.01). Cross-sectional mediation analyses demonstrated that the association between ADT and objectively and subjectively measured sleep disturbance was partly attributable to nocturia and hot flashes (Ps<.05). CONCLUSIONS: The results of the current study suggest that the association between ADT and sleep may be partly explained by nocturia and hot flash interference. Future studies should examine behavioral and pharmacologic interventions to address these symptoms among ADT recipients. Cancer 2018;124:499-506. © 2017 American Cancer Society.

Late Effects After Radiotherapy for Childhood Low-grade Glioma.

OBJECTIVES: This single-institution report describes long-term disease control and late effects in pediatric patients with low-grade glioma (LGG) following radiotherapy (RT). MATERIALS AND METHODS: Twenty-nine pediatric patients with LGG were treated with photon-based RT from 1970 to 2004 (mean age at time of RT, 9.8 y; range, 0.6 to 19 y). One patient underwent gross total resection, 25 underwent subtotal resection or biopsy, and 3 were treated based on radiographic characteristics alone. Three patients underwent chemotherapy before RT. The median RT dose was 54 Gy (range, 40 to 55 Gy). RESULTS: The median follow-up was 17.8 years (range, 1.6 to 36.8 y) for all patients and 19.9 years (range, 1.6 to 36.8 y) for all living patients. The 5-, 10-, and 20-year local control and progression-free survival rates were equivalent at 82%, 74%, and 63%, respectively. The 5-, 10-, and 20-year cause-specific survival and overall survival rates were equivalent at 89%, 85%, and 58%, respectively. On univariate analysis, age below 4 years during treatment was associated with significantly inferior local control (P=0.0067), cause-specific survival (P=0.0021), and overall survival (P=0.0021). Of the 23 survivors analyzed for late toxicity, 15 (65%) developed grade 3+ toxicity. The most common Common Terminology Criteria for Adverse Events grade 3 toxicity (30% of survivors) was serious cognitive disability. Four patients (14%) died secondary to treatment complications, all occurring over a decade after completing RT. CONCLUSIONS: Over half of children diagnosed with LGG survive >20 years after RT; this report reveals the chronicity of toxicity beyond the typically reported follow-up. Our findings inform the therapeutic ratio of RT in this disease and may help guide late-effect screening recommendations.

Phase 1 Study of Ipilimumab Combined With Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients With Brain Metastases.

PURPOSE: We performed a phase 1 study to determine the maximum tolerable dose and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) in patients with brain metastases from melanoma. METHODS AND MATERIALS: Based on the intracranial disease burden, patients underwent WBRT (arm A) or SRS (arm B). The ipilimumab starting dose was 3 mg/kg every 3 weeks, starting on day 3 of WBRT or 2 days after SRS. The ipilimumab dose was escalated to 10 mg/kg using a 2-stage, 3+3 design. The primary endpoint was to determine the maximum tolerable dose of ipilimumab combined with radiation therapy. The secondary endpoints were overall survival, intracranial and extracranial control, progression-free survival, and toxicity. The ClinicalTrials.gov registration number is NCT01703507. RESULTS: The characteristics of the 16 patients enrolled between 2011 and 2014 were mean age, 60 years; median number of brain metastases, 2 (range 1->10); and number with EC disease, 13 (81%). Treatment included WBRT (n=5), SRS (n=11), and ipilimumab 3 mg/kg (n=7) or 10 mg/kg (n=9). The median follow-up was 8 months (arm A) and 10.5 months (arm B). A total of 21 grade 1 to 2 neurotoxic effects occurred, with no dose-limiting toxicities. One patient experienced grade 3 neurotoxicity before ipilimumab administration. Ten additional grade 3 toxicities were reported, with gastrointestinal toxicities (n=5; 31%) the most common. No patient developed grade 4 or 5 toxicity. The median progression-free survival and overall survival in arm A was 2.5 months and 8 months and in arm B was 2.1 months and not reached, respectively. CONCLUSIONS: Concurrent ipilimumab 10 mg/kg with SRS is safe. The WBRT arm was closed early because of slow accrual but demonstrated safety with ipilimumab 3 mg/kg. No patient experienced dose-limiting toxicity. Larger studies, including those with combination checkpoint inhibitor therapy and SRS, are warranted.

The Role of Genomic Techniques in Predicting Response to Radiation Therapy.

The understanding of the relationship between genetic variation and an individual patient's response to radiation therapy (RT) has gained significant ground over the past several years. Genetic markers have been identified that could ultimately serve as the foundation for predictive models in clinical practice, and that hold the potential to revolutionize the delivery of precision medicine in oncology. Single nucleotide polymorphisms, single genes, and/or gene signatures could ultimately serve as the basis for patient stratification in prospective clinical trials. Currently, molecular markers relevant to breast, lung, and head and neck cancers have been integrated into clinical practice and serve as predictive tools to guide systemic therapy. In the future, the use of predictive models based on genomic determinants may become standard practice in radiation oncology, offering the potential to further personalize the delivery of RT and optimize the therapeutic ratio.

Management of Stage I Lung Cancer with Stereotactic Ablative Radiation Therapy.

Early stage non-small cell lung cancer is a growing clinical entity with evolving standards of care. With the adoption of lung screening guidelines, the incidence of early stage disease is expected to increase. Surgical resection for early stage disease has been considered standard of care; however, there is evidence that stereotactic ablative radiation therapy (SABR) may be a viable alternate to surgery. In the last decade, advances in image guidance, treatment planning systems, and improved spatial accuracy of treatment delivery have converged to result in the effective use of SABR in the treatment of early stage lung cancer.

Radioisotopes in management of metastatic prostate cancer.

INTRODUCTION: Metastatic prostate cancer continues to be a leading cause of morbidity and mortality in men with prostate cancer. Over the last decade, the treatment landscape for patients with castrate-resistant disease has drastically changed, with several novel agents demonstrating an improvement in overall survival in large, multi-institutional randomized trials. Traditional treatment with radioisotopes has largely been in the palliative setting. However, the first in class radiopharmaceutical radium-223 has emerged as the only bone-directed treatment option demonstrating an improvement in overall survival. METHODS: Medline publications from 1990 to 2016 were searched and reviewed to assess the use of currently approved radioisotopes in the management of prostate cancer including emerging data regarding integration with novel systemic therapies. New positron emission tomography-based radiotracers for advanced molecular imaging of prostate cancer were also queried. RESULTS: Radioisotopes play a crucial role in the diagnosis and treatment of prostate cancer in the definitive and metastatic setting. Molecular imaging of prostate cancer and theranostics are currently being investigated in the clinical arena. CONCLUSIONS: The use of modern radioisotopes in selected patients with mCRPC is associated with improvements in overall survival, pain control, and quality of life.

Brain Metastases in Patients with Gynecologic Cancers: A Single Institution Experience and Review of the Literature.

OBJECTIVE: Brain Metastasis (BM) from primary gynecologic cancers is a rare entity. The advances and successes in the treatment of primary gynecologic malignancies, have led to prolonged survival and, a higher incidence of BM. This study aims to report the experience at our institution in managing these patients, and provide possible data points that may be essential to note as prognostic factors, and see if our findings are consistent with the literature in this subject. We also aim to provide a brief literature review of patients with gynecologic cancers and BM. METHODS: This is a small single institution retrospective study of 23 patients with a gynecologic malignancy and BM, identified between the years 2007-2015. Data were collected on variables including patient demographics, disease and treatment. RESULTS: The median overall survival from the primary diagnosis was 28 months. Median time from diagnosis of BM to death was 9 months. CONCLUSION: The outcomes in our study are similar to what is stated in the current literature with regard to BM from gynecologic malignancies. Our literature search also revealed that the molecular analysis and treatment of the primary tumor remain important to prevent BMs. The tendency of tumors to metastasize varies for one tumor type to another for the same type of tumor. The tendency to develop BM may not only depend on risk factors such as stage, grade, and histology, but also on the genetic profile of the primary tumor. The study suggests that multimodal treatment of BM has better outcomes in managing BM from gynecologic cancers.

Hepatoid Carcinoma of the Pancreas: A Case Report and Review of the Literature.

Background: Hepatoid carcinoma (HC) is a rare extrahepatic malignancy that shares many morphological and serological features with hepatocellular carcinoma. HC has been reported to arise from several organs that are derived from the foregut endoderm, including the stomach, gallbladder, and pancreas. We present a case of an elderly man with hepatoid adenocarcinoma of the pancreatic head with duodenal invasion, presenting with pancreatitis and a gastrointestinal bleed. With only 23 reported cases at the time of our literature search, we discuss the presentation, histopathology, and management of such a rare disease. Case presentation: A 71-year-old man presented initially with abdominal pain and was treated conservatively for pancreatitis. Four months later, he presented with melena and anemia. His examination was noncontributory. Esophagogastroduodenoscopy revealed a friable ampulla of Vater, and a CT scan of the abdomen showed a 4.5 cm pancreatic head mass. Fine needle aspirate revealed an epithelioid neoplasm with hepatoid morphology. Serum α-fetoprotein was normal. Surgical resection confirmed hepatoid adenocarcinoma of the pancreas with positive lymphadenopathy and negative margins. There was no radiographical or gross evidence of distant spread. Observation and adjuvant gemcitabine were discussed as possible options. The patient elected to receive care closer to home and will continue surveillance imaging. Conclusion: With only 23 reported cases, pancreatic HC represents a rare entity within gastrointestinal oncology. There is no clear postoperative adjuvant standard therapy for this likely heterogeneous group of tumors. Although surgical resection is the mainstay of upfront treatment, metastatic disease to the lymph nodes or liver portends a poor prognosis and may warrant treatment such as transarterial embolization, chemotherapy, or radiotherapy.

Novel use of topical dapsone 5% gel for erythema elevatum diutinum: safer and effective.

We present a case of an otherwise healthy 81-year-old gentleman with multiple asymptomatic, erythematous, indurated papules and plaques, ranging in size from 0.5 to 1.5 cm, involving the dorsal, lateral, and palmar surfaces of the fingers bilaterally. A clinical suspicion of erythema elevatum diutinum (EED) led to initial treatment with topical dapsone 5% gel (ACZONE; Allergan Inc, Irvine, CA). Lesional biopsy demonstrated a dense perivascular infiltration of polymorphonuclear leukocytes and chronic inflammatory cells with perivascular fibrin deposition. Focal neutrophilic infiltration of superficial dermal blood vessel walls was present, suggesting a leukocytoclastic vasculitis. Stains for bacteria and fungi were negative. Clinicopathologic findings were consistent with EED, and in the interim, improvement with topical dapsone 5% gel was noted. Addition of oral dapsone led to complete resolution of the lesions. We present this case to illustrate the subtle, indolent clinical presentation of EED and demonstrate the uncomplicated use of topical dapsone 5% gel for rapid improvement and subsequent successful treatment of localized disease.