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CONTEXT: Half of the patients with cancer who undergo radiation therapy do so with palliative intent. OBJECTIVES: To determine the proportion of undergoing radiation in the last month of life, patient characteristics, cancer course, the type and duration of radiation, whether palliative care was involved, and the of radiation with aggressive cancer care metrics. METHODS: One thousand seven hundred twenty-seven patients who died of cancer between January 1, 2018, and December 31, 2019, were included. Demographics, cancer stage, palliative care referral, advance directives, use of home health care, radiation timing, and survival were collected. Type of radiation, course, and intent were reviewed. Chi-square analysis was utilized for categorical variables, and Kruskal-Wallis tests for continuous variables. A stepwise selection was used to build a Cox proportional hazard model. RESULTS: Two hundred thirty-three patients underwent radiation in the last month of life. Younger patients underwent radiation 67.3 years (SD 11.52) versus 69.2 years (SD 11.96). 42.6% had radiation within two weeks of death. The average fraction number was 5.5. Individuals undergoing radiation were more likely to start chemotherapy within the last 30 days of life, continue chemotherapy within two weeks of death, be admitted to the ICU, and have two or more hospitalizations or emergency room visits. Survival measured from the date of diagnosis was shorter for those undergoing radiation, 122 days (IQR 58-462) versus 474 days (IQR 225-1150). Palliative care consultations occurred later in those undergoing radiation therapy. CONCLUSION: Radiation therapy in the last month of life occurs in younger patients with rapidly progressive cancer, who are subject to more aggressive cancer care, and have late palliative care consults.
Subject(s)
Neoplasms , Terminal Care , Humans , Palliative Care , Neoplasms/radiotherapy , Neoplasms/drug therapy , Hospitalization , Death , Retrospective StudiesABSTRACT
PURPOSE: Utilization of breathhold scans with live tracking has a long track record of good published outcomes for stereotactic body radiation therapy (SBRT) and is recommended by the manufacturer of the Synchrony tracking system. However, the popularity of four-dimensional computed tomography (4DCT) scans challenges the validity of the breathhold scan with live tracking technique. Although this study is not intended to prove the superiority of either method, we demonstrate the feasibility of using the breathhold scans with a phantom test and clinical examples. METHODS: A 4DCT of a perfect sphere was scanned at 20 breaths per minute and compared to a 4DCT of a small lung tumor in one patient and a 4DCT of a larger renal tumor in another patient, as well as to fiducial matching in a patient with pancreatic cancer. Normal exhale and normal inhale breathhold CT scans were performed for the pancreatic cancer patient, combined with Synchrony tracking on CyberKnife (Sunnyvale, CA: Accuray) for treatment. RESULTS: The 4DCT scan of the phantom exhibited considerable apparent deformation, which must be entirely due to imaging artifact since the perfect sphere in the phantom is known to be completely rigid. The 4DCT of the lung and renal tumors in patients had similar apparent deformation. Usually in patients, from 4DCT alone, it is difficult to determine how much was due to deformation and how much was due to artifact. Fiducial positions in the final normal exhale and normal inhale breathhold scans for Synchrony matched each other within 1mm for the pancreatic cancer patient. CONCLUSION: We demonstrated the feasibility of breathhold scans with Synchrony live tracking, as recommended by the manufacturer. More studies will be needed to determine whether this method is better than using a 4DCT.
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Importance: Currently, there are limited published data regarding resource use and spending on cancer care in the US. Objective: To characterize the most frequent medical services provided and the associated spending for privately insured patients with cancer in the US. Design, Setting, and Participants: This cohort study used data from the MarketScan database for the calendar year 2018 from a sample of 27.1 million privately insured individuals, including patients with a diagnosis of the 15 most prevalent cancers, predominantly from large insurers and self-insured employers. Overall societal health care spending was estimated for each cancer type by multiplying the mean total spending per patient (estimated from MarketScan) by the number of privately insured patients living with that cancer in 2018, as reported by the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Analyses were performed from February 1, 2018, to July 8, 2021. Exposures: Evaluation and management as prescribed by treating care team. Main Outcomes and Measures: Current Procedural Terminology and Healthcare Common Procedure Coding System codes based on cancer diagnosis code. Results: The estimated cost of cancer care in 2018 for 402â¯115 patients with the 15 most prevalent cancer types was approximately $156.2 billion for privately insured adults younger than 65 years in the US. There were a total of 38.4 million documented procedure codes for 15 cancers in the MarketScan database, totaling $10.8 billion. Patients with breast cancer contributed the greatest total number of services (10.9 million [28.4%]), followed by those with colorectal cancer (3.9 million [10.2%]) and prostate cancer (3.6 million [9.4%]). Pathology and laboratory tests contributed the highest number of services performed (11.7 million [30.5%]), followed by medical services (6.3 million [16.4%]) and medical supplies and nonphysician services (6.1 million [15.9%]). The costliest cancers were those of the breast ($3.4 billion [31.5%]), followed by lung ($1.1 billion [10.2%]) and colorectum ($1.1 billion [10.2%]). Medical supplies and nonphysician services contributed the highest total spent ($4.0 billion [37.0%]), followed by radiology ($2.1 billion [19.4%]) and surgery ($1.8 billion [16.7%]). Conclusions and Relevance: This analysis suggests that patients with breast, colorectal, and prostate cancers had the greatest number of services performed, particularly for pathology and laboratory tests, whereas patients with breast, lung, lymphoma, and colorectal cancer incurred the greatest costs, particularly for medical supplies and nonphysician services. The cost of cancer care in 2018 for the 15 most prevalent cancer types was estimated to be approximately $156.2 billion for privately insured adults younger than 65 years in the US.
Subject(s)
For-Profit Insurance Plans/standards , Health Care Costs/statistics & numerical data , Neoplasms/economics , Patient Acceptance of Health Care/statistics & numerical data , Adult , Cohort Studies , Female , For-Profit Insurance Plans/statistics & numerical data , Humans , Male , Middle Aged , Neoplasms/epidemiology , United States/epidemiologySubject(s)
Esthesioneuroblastoma, Olfactory/drug therapy , Indazoles/therapeutic use , Nasal Cavity , Neoplasm Recurrence, Local/drug therapy , Nose Neoplasms/drug therapy , Pyrimidines/therapeutic use , Sulfonamides/therapeutic use , Aged , Esthesioneuroblastoma, Olfactory/genetics , Esthesioneuroblastoma, Olfactory/secondary , Female , Fumarate Hydratase/genetics , Humans , Mutation , Nose Neoplasms/genetics , Nose Neoplasms/pathology , Remission Induction , Retreatment , Time FactorsABSTRACT
BACKGROUND: The human embryo or foetus is susceptible to harmful effects of radiation, which include growth delay, malformations, impaired cognitive function, cancer and foetal demise. The purpose of this study is to describe pregnancy screening practices in radiation oncology, so that potential health effects may be avoided and areas of prevention may be identified. METHODS: An electronic survey was delivered to 6,304 members of the American Society for Radiation Oncology. The survey subjects were radiation oncologists who are currently practicing in the world. Chi-square tests and a multiple logistic regression model were used to analyse the data. All tests were two-sided and the statistical significance level used was 0.05. This study (STUDY00009765) was approved by an Institutional Review Board. RESULTS: A total of 434 responses from practicing radiation oncologists were received. Of these respondents, 69.1% were practicing in the United States. Of all respondents, 19.8% reported treating paediatric patients and 93.6% reported treating premenopausal patients. Despite 84.8% of radiation oncologists saying they would 'strongly agree' or 'agree' that one should screen for pregnancy prior to radiation therapy, 29.7% of respondents reported their department has no screening policy and 7.1% of respondents reported they do not screen for pregnancy. Having a departmental policy was associated with screening for pregnancy (p-value = 0.0005).Of all respondents, 93 reported treating a known pregnant patient. Of these 93 respondents, 76 reported intentionally treating and 17 reported accidentally treating a pregnant patient. Respondents who did not screen at time of simulation were significantly more likely to treat a pregnant patient than those who screened at time of simulation (p-value = 0.0459). CONCLUSIONS: Heterogeneity exists among practicing radiation oncologists regarding pregnancy screening. Institutional policies should be clear and consistent. All members of the radiation oncology team should make every effort to minimise unintended radiation exposure to the embryo or foetus.
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BACKGROUND: Prior comparisons of brain arteriovenous malformations (AVMs) treated using stereotactic radiosurgery (SRS) with or without embolization were inherently flawed, due to differences in the pretreatment nidus volumes. OBJECTIVE: To compare the outcomes of embolization and SRS, vs SRS alone for AVMs using pre-embolization malformation features. METHODS: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Patients were categorized into the embolization and SRS (E + SRS) or SRS alone (SRS-only) cohorts. The 2 cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was defined as AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiologic and symptomatic radiation-induced changes (RIC), and cyst formation. RESULTS: The matched cohorts each comprised 101 patients. Crude AVM obliteration rates were similar between the matched E + SRS vs SRS-only cohorts (48.5% vs 54.5%; odds ratio = 0.788, P = .399). Cumulative probabilities of obliteration at 3, 4, 5, and 6 yr were also similar between the E + SRS (33.0%, 46.4%, 56.2%, and 60.8%, respectively) and SRS-only (32.9%, 46.2%, 56.0%, and 60.6%, respectively) cohorts (subhazard ratio (SHR) = 1.005, P = .981). Cumulative probabilities of radiologic RIC at 3, 4, 5, and 6 yr were lower in the E + SRS (25.0%, 25.7%, 26.7%, and 26.7%, respectively) vs SRS-only (45.3%, 46.2%, 47.8%, and 47.8%, respectively) cohort (SHR = 0.478, P = .004). Symptomatic and asymptomatic embolization-related complication rates were 8.3% and 18.6%, respectively. Rates of post-SRS hemorrhage, all-cause mortality, symptomatic RIC, and cyst formation were similar between the matched cohorts. CONCLUSION: This study refutes the prevalent notion that AVM embolization negatively affects the likelihood of obliteration after SRS.
Subject(s)
Embolization, Therapeutic/methods , Intracranial Arteriovenous Malformations/therapy , Radiosurgery/methods , Adult , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Embolization of brain arteriovenous malformations (AVMs) using ethylene-vinyl alcohol copolymer (Onyx) embolization may influence the treatment effects of stereotactic radiosurgery (SRS) differently than other embolysates. OBJECTIVE: To compare the outcomes of pre-SRS AVM embolization with vs without Onyx through a multicenter, retrospective matched cohort study. METHODS: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Embolized AVMs treated with SRS were selected and categorized based on embolysate usage into Onyx embolization (OE + SRS) or non-Onyx embolization (NOE + SRS) cohorts. The 2 cohorts were matched in a 1:1 ratio using de novo AVM features for comparative analysis of outcomes. RESULTS: The matched cohorts each comprised 45 patients. Crude AVM obliteration rates were similar between the matched OE + SRS vs NOE + SRS cohorts (47% vs 51%; odds ratio [OR] = 0.837, P = .673). Cumulative probabilities of obliteration were also similar between the OE + SRS vs NOE + SRS cohorts (subhazard ratio = 0.992, P = .980). Rates of post-SRS hemorrhage, all-cause mortality, radiation-induced changes, cyst formation, and embolization-associated complications were similar between the matched cohorts. Sensitivity analysis for AVMs in the OE + SRS cohort embolized with Onyx alone revealed a higher rate of asymptomatic embolization-associated complications in this subgroup compared to the NOE + SRS cohort (36% vs 15%; OR = 3.297, P = .034), but the symptomatic complication rates were similar. CONCLUSION: Nidal embolization using Onyx does not appear to differentially impact the outcomes of AVM SRS compared with non-Onyx embolysates. The embolic agent selected for pre-SRS AVM embolization should reflect both the experience of the neurointerventionalist and target of endovascular intervention.
Subject(s)
Embolization, Therapeutic/methods , Intracranial Arteriovenous Malformations/therapy , Polyvinyls/therapeutic use , Radiosurgery , Adolescent , Adult , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: Investigations of the combined effects of neoadjuvant Onyx embolization and stereotactic radiosurgery (SRS) on brain arteriovenous malformations (AVMs) have not accounted for initial angioarchitectural features prior to neuroendovascular intervention. The aim of this retrospective, multicenter matched cohort study is to compare the outcomes of SRS with versus without upfront Onyx embolization for AVMs using de novo characteristics of the preembolized nidus. METHODS: The International Radiosurgery Research Foundation AVM databases from 1987 to 2018 were retrospectively reviewed. Patients were categorized based on AVM treatment approach into Onyx embolization (OE) and SRS (OE+SRS) or SRS alone (SRS-only) cohorts and then propensity score matched in a 1:1 ratio. The primary outcome was AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiological and symptomatic radiation-induced changes (RICs), and cyst formation. Comparisons were analyzed using crude rates and cumulative probabilities adjusted for competing risk of death. RESULTS: The matched OE+SRS and SRS-only cohorts each comprised 53 patients. Crude rates (37.7% vs 47.2% for the OE+SRS vs SRS-only cohorts, respectively; OR 0.679, p = 0.327) and cumulative probabilities at 3, 4, 5, and 6 years (33.7%, 44.1%, 57.5%, and 65.7% for the OE+SRS cohort vs 34.8%, 45.5%, 59.0%, and 67.1% for the SRS-only cohort, respectively; subhazard ratio 0.961, p = 0.896) of AVM obliteration were similar between the matched cohorts. The secondary outcomes of the matched cohorts were also similar. Asymptomatic and symptomatic embolization-related complication rates in the matched OE+SRS cohort were 18.9% and 9.4%, respectively. CONCLUSIONS: Pre-SRS AVM embolization with Onyx does not appear to negatively influence outcomes after SRS. These analyses, based on de novo nidal characteristics, thereby refute previous studies that found detrimental effects of Onyx embolization on SRS-induced AVM obliteration. However, given the risks incurred by nidal embolization using Onyx, this neoadjuvant intervention should be used judiciously in multimodal treatment strategies involving SRS for appropriately selected large-volume or angioarchitecturally high-risk AVMs.
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BACKGROUND AND PURPOSE: Immune checkpoint inhibitor with radiation therapy (ICI + RT) is under investigation for improved patient outcome, so we performed a systematic review/meta-analysis of toxicities for ICI + RT compared to immune checkpoint inhibitor (ICI) therapy alone. MATERIALS AND METHODS: A PRISMA-compliant systematic review of studies in MEDLINE (PubMed) and in the National Comprehensive Cancer Network guidelines was conducted, with primary outcome grade 3 + toxicity. Criteria for ICI alone were: phase III/IV trials that compared immunotherapy to placebo, chemotherapy, or alternative immunotherapy; and for ICI + RT: prospective/retrospective studies with an arm treated with ICI + RT. Meta-analysis was performed by random effects models using the DerSimonian and Laird method. The I2 statistic and Cochran's Q test were used to assess heterogeneity, while funnel plots and Egger's test assessed publication bias. RESULTS: This meta-analysis included 51 studies (n = 15,398), with 35 ICI alone (n = 13,956) and 16 ICI + RT studies (n = 1,442). Our models showed comparable grade 3-4 toxicities in ICI + RT (16.3%; 95% CI, 11.1-22.3%) and ICI alone (22.3%; 95% CI, 18.1-26.9%). Stratification by timing of radiation and irradiated site showed no significant differences, but anti-CTLA-4 therapy and melanoma showed increased toxicity. The grade 5 toxicities were 1.1% and 1.9% for ICI alone and ICI + RT respectively. There was significant heterogeneity, but not publication bias. CONCLUSIONS: The random effects model showed comparable grade 3-4 toxicity in using ICI + RT compared to ICI alone in CNS melanoma metastases, NSCLC, and prostate cancer. ICI + RT is safe for future clinical trials in these cancers.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Immune Checkpoint Inhibitors , Male , Prospective Studies , Retrospective StudiesABSTRACT
BACKGROUND: The objectives of this study were to characterize the risk of death (1) from the primary cancer vs competing cause of death; and (2) from various causes of death vs the general poplation. The relative risk of death after a pediatric cancer diagnosis versus the general population and the risk of death from a primary cancer diagnosis versus competing causes of death. METHODS: This retrospective, population-based study used the Surveillance, Epidemiology, and End Results database (1980-2015) and included patients aged 0 to 19 years at the time of diagnosis. Observed deaths were calculated; the risk of death versus the general population was assessed with standardized mortality ratios (SMRs). Competing risk models for the cause of death were performed. RESULTS: There were 58,356 patients who were diagnosed, and the mortality rate was 22.8%. To assess causes of death, 6996 patients who died during the study period were included (45,580 total person-years at risk): 5128 (73%) died of their primary cancer, and 1868 (27%) died of a competing cause. Among all patients, the rate of death from the index cancer was higher than the rate of death from another cause within the first 5 years after diagnosis. The risk of death from a nonprimary cancer began to supersede the rate of death from the primary cancer 10 years after diagnosis for patients with germ cell tumors, lymphomas, and sarcomas. SMRs for the primary cancer were highest within the first 5 years after diagnosis for all cancers (SMRs, 100-50,000; P < .0001). The risk of death from competing causes (heart disease, suicide, and sepsis) was elevated (SMR, >100; P < .001). The risk of dying of heart disease was high, especially for patients with astrocytomas (SMR, 47.84; 95% confidence interval [CI], 27.87-76.59) and neuroblastomas (SMR, 98.59; 95% CI, 47.28-181.32). The risk of dying of suicide was high in most patients, particularly for those with osteosarcomas (SMR, 111.40; 95% CI, 2.82-620.69), Hodgkin lymphomas (SMR, 62.35; 95% CI, 34.89-102.83), and gonadal germ cell tumors (SMR, 28.97; 95% CI, 12.51-57.09). CONCLUSIONS: The cause of death for patients with gonadal germ cell tumors, lymphomas, and sarcomas is more commonly a secondary cancer or noncancerous cause than the primary disease; their risk of death from competing causes (heart disease, suicide, and sepsis) rises throughout life.
Subject(s)
Cause of Death , Neoplasms, Second Primary/mortality , Neoplasms/mortality , Pediatrics/trends , Adolescent , Adult , Child , Child, Preschool , Databases, Factual , Hodgkin Disease/mortality , Hodgkin Disease/psychology , Humans , Infant , Infant, Newborn , Male , Neoplasms/pathology , Neoplasms/psychology , Neoplasms, Second Primary/pathology , Retrospective Studies , Suicide/psychology , Time Factors , Young AdultABSTRACT
Pancreatic cancer is a highly fatal malignancy for which surgery is currently considered to be the only curative treatment. However, less than a quarter of patients have disease amenable to definitive surgical resection. Local treatment with radiation therapy is a promising alternative to surgery for those patients with unresectable disease. However, conventional radiation techniques with computed tomography (CT)-guided therapy have yielded disappointing results due to the inability to deliver ablative doses of ionizing radiation, while sparing the radiosensitive adjacent organs at risk. Magnetic resonance-guided radiotherapy (MRgRT) has emerged as an alternative to CT-guided radiation treatment which allows for the delivery of higher doses of radiation with low toxicity to surrounding structures. Further study into the use of MRgRT and dose escalation for locally advanced unresectable pancreatic cancer is needed.
Subject(s)
Magnetic Resonance Imaging , Pancreatic Neoplasms/radiotherapy , Radiation Injuries/prevention & control , Radiotherapy, Image-Guided , Animals , Humans , Organs at Risk/radiation effects , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/pathology , Patient Safety , Protective Factors , Radiation Dosage , Radiotherapy, Image-Guided/adverse effects , Risk Assessment , Risk Factors , Treatment OutcomeABSTRACT
We identify cancer patients at highest risk of fatal stroke. This is a population-based study using nationally representative data from the Surveillance, Epidemiology, and End Results program, 1992-2015. Among 7,529,481 cancer patients, 80,513 died of fatal stroke (with 262,461 person-years at risk); the rate of fatal stroke was 21.64 per 100,000-person years, and the standardized mortality ratio (SMR) of fatal stroke was 2.17 (95% CI, 2.15, 2.19). Patients with cancer of the prostate, breast, and colorectum contribute to the plurality of cancer patients dying of fatal stroke. Brain and gastrointestinal cancer patients had the highest SMRs (>2-5) through the follow up period. Among those diagnosed at <40 years of age, the plurality of strokes occurs in patients treated for brain tumors and lymphomas; if >40, from cancers of the prostate, breast, and colorectum. For almost all cancers survivors, the risk of stroke increases with time.
Subject(s)
Neoplasms/complications , Stroke/epidemiology , Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/mortality , Risk Factors , Stroke/etiology , Stroke/mortality , Survivors/statistics & numerical data , Young AdultABSTRACT
Cancers of the digestive system remain highly lethal; therefore, the care of patients with malignant diseases of the digestive tract requires the expertise of providers from multiple health disciplines. Progress has been made to advance the understanding of epidemiology and genetics, diagnostic and screening evaluation, treatment modalities, and supportive care for patients with gastrointestinal cancers. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference at the Hershey Country Club in Hershey, Pennsylvania on 29 September 2017, the faculty members of the Penn State Health Milton S. Hershey Medical Center presented a variety of topics that focused on this oncological specialty. In this continuing medical education-certified conference, updates on the population sciences including health disparities and resistance training were presented. Progress made in various diagnostic evaluation and screening procedures was outlined. New developments in therapeutic modalities in surgical, radiation, and medical oncology were discussed. Cancer genetic testing and counseling and the supportive roles of music and arts in health and cancer were demonstrated. In summary, this disease-focused medical conference highlighted the new frontiers in gastrointestinal oncology, and showcase the multi-disciplinary care provided at the Penn State Cancer Institute.
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The role of external beam radiation therapy (EBRT) in the management of upper gastrointestinal malignancies is constantly evolving. As radiation therapy techniques improve and are able to deliver more ablative doses of radiotherapy while sparing healthy tissue, radiation can be applied to a wider range of clinical scenarios. Stereotactic body radiation therapy (SBRT) allows a high dose of radiation to be delivered to a highly conformal treatment volume in a short amount of time. Another potential advantage of SBRT is its ability to increase tumor immunogenicity, while also having less of an immunosuppressive effect on the patient, as compared to conventionally fractionated radiation therapy. In so doing, SBRT may potentiate the effects of immune therapy when the two treatments are combined, thus improving therapeutic outcomes. This article provides an overview of the role of SBRT in the management of upper gastrointestinal GI malignancies and the emerging data on immune biomarkers and SBRT, with a focus on pancreatic and liver cancer.
ABSTRACT
There is currently no clear distinction between the treatment of HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC). HPV-positive OPSCC has been demonstrated to be more radiosensitive than its HPV-negative counterpart. Despite this, patients with HPV-positive OPSCC continue to receive a full dose of radiation (70 Gy) outside clinical trials. However, this high dose comes with considerable morbidities, including severe mucositis, dysphagia, and xerostomia. We describe the cases of 2 patients with HPV-positive OPSCC who received two cycles of high-dose cisplatin at 100 mg/m2 on 3 separate days, along with concurrent radiotherapy at 50 Gy in 25 fractions for one and 46 Gy in 23 fractions for the other. During treatment, both patients experienced significant acute-phase toxicities-including grade 3 mucositis, grade 3 nausea, and grade 2 dermatitis-and their treatment regimen was stopped before its planned completion. Nevertheless, after a follow-up of 75 and 78 months, respectively, neither patient exhibited any evidence of disease. Late toxicities included grade 1 xerostomia, grade 1 pharyngeal-phase dysphagia, and grade 1 dysgeusia with some foods. We conclude that de-escalating the dose of radiation for HPV-positive patients by 30% and identifying which patients can safely be treated with this level of dose reduction warrants further study.
Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy/methods , Cisplatin/administration & dosage , Oropharyngeal Neoplasms/therapy , Antineoplastic Agents/adverse effects , Carcinoma, Squamous Cell/virology , Chemoradiotherapy/adverse effects , Cisplatin/adverse effects , Disease-Free Survival , Dose-Response Relationship, Radiation , Humans , Male , Middle Aged , Oropharyngeal Neoplasms/virology , Treatment Outcome , Withholding TreatmentABSTRACT
There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not. We then evaluated the treatment response following completion of ipilimumab. A total of 101 patients received ipilimumab in the prespecified time frame. 70 received Ipi-RT and 31 received ipilimumab without concurrent radiotherapy. Median overall survival (OS) was significantly increased in the concurrent Ipi-RT arm at 19 months vs. 10 months for ipilimumab alone (p = 0.01). Median progression free survival (PFS) was marginally increased in the Ipi-RT group compare with the ipilimumab alone group (5 months vs. 3 months, p = 0.20). Rates of complete response (CR) were significantly increased in the Ipi-RT group vs. ipilimumab alone (25.7% vs. 6.5%; p = 0.04), and rates of overall response (OR) in the groups were 37.1% vs. 19.4% (p = 0.11). No increase in toxicities was observed in the Ipi-RT group compare with ipilimumab alone. Prospective trials are needed to further clarify the role of radiotherapy with ipilimumab, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Melanoma/drug therapy , Melanoma/radiotherapy , Adult , Aged , Aged, 80 and over , Chemoradiotherapy , Female , Humans , Ipilimumab , Male , Middle Aged , Retrospective Studies , Survival AnalysisABSTRACT
One of the defining characteristics of the malignant phenotype is the ability to evade the host immune system. Immunotherapy as a treatment modality represents a new dawn in the way we think about the treatment of a variety of malignancies. The story of immunotherapy traces its roots to its relationship with malignant melanoma. In this article, we review the intertwined history of immunotherapy and melanoma, including the early significant history, a discussion on immune mechanisms, resistance, local and systemic immunotherapeutic modalities, and speculate on possible novel future treatment options.
Subject(s)
Immunotherapy/methods , Melanoma/therapy , Skin Neoplasms/therapy , Animals , Humans , Melanoma/immunology , Skin Neoplasms/immunologyABSTRACT
Melanoma is a significant clinical problem, with rising rates of incidence. Surgery is the mainstay of treatment. The role of adjuvant radiotherapy in the control of locoregionally advanced cutaneous melanoma is controversial. A retrospective study of the Surveillance, Epidemiology, and End Results (SEER) database was performed. Patients with locoregionally confined cutaneous melanoma treated surgically between 2004 and 2009 were evaluated, with cancer-specific and all-cause mortality as primary end points. Propensity score matching was used to match 319 radiotherapy patients with 319 non-radiotherapy controls, stratifying by head and neck (HN) and non-head and neck (NHN) primary. Surgery was primarily by wide excision in both the radiotherapy (51.72%) and non-radiotherapy (53.91%) groups. The majority had nodal disease (82.13% vs. 82.44%). White (91.22% vs. 90.59%) males (70.21% vs. 68.96%) predominated. Average ages at diagnosis were 62.27 (SD 15.93) and 63.02 (SD 16.03). Using Cox proportional hazards models, radiation conferred decreased survival in all-cause (HR 1.44, p < 0.0003), and cancer specific mortality (HR 1.57, p < 0.0002) in combined analysis. The NHN group showed significantly decreased 6-year cancer specific survival (HR 2.05, p < 0.0001) for radiated patients. The HN group showed a non-significant hazard with radiotherapy (HR 1.19, p = 0.307). Meaningful differences not captured in the SEER database may exist between cohorts. Based on available SEER data, routine use of adjuvant radiotherapy should be viewed with caution and reserved for high-risk patients. Future trials evaluating patient quality of life may clarify the benefit of adjuvant radiotherapy in high-risk melanoma populations.
ABSTRACT
Primary breast sarcoma (PBS) is a rare and heterogeneous group of malignancies with limited publications. We obtained data from the Surveillance, Epidemiology, and End Results Program and performed analysis to determine clinicopathological characteristics of PBS and estimate their associations with overall survival (OS) and cancer-specific survival (CSS). Median age of PBS was 55-59 years and median OS was 108 months. Age, overlap or entire breast involvement, tumor histology, and tumor spread were associated with poor survival outcomes. In the multivariable analysis, tumor size, lymph node involvement, distant metastasis and histologic grade were correlated with survival outcomes (P < 0.001). In M0 patients, mastectomy was associated with worse survival outcomes compared with breast conservative surgery (BCS) (adjusted hazard ratio [adjHR], 1.80; 95% CI, 1.31-2.47), regardless of tumor size, tumor grade, tumor histology or radiation history. Adjuvant radiation improved survival outcomes in patients with tumor size >5 cm (adjHR, 0.63; 95% CI, 0.43-0.91), but not in patients with tumor size ≤ 5 cm. Our study demonstrated clinicopathological characteristics of PBS in the US population and supports performing BCS if R0 resection can be achieved, with radiation if tumor size is over 5 cm.