147 research outputs found
Toward an improved understanding of the ionizing radiation induced DNA damage/response networks in human malignancies.
Reirradiation practices for children with diffuse intrinsic pontine glioma
Background: Diffuse intrinsic pontine gliomas (DIPGs) are a leading cause of brain tumor deaths in children. Current standard of care includes focal radiation therapy (RT). Despite clinical improvement in most patients, the effect is temporary and median survival is less than 1 year. The use and benefit of reirradiation have been reported in progressive DIPG, yet standardized approaches are lacking. We conducted a survey to assess reirradiation practices for DIPG in North America. Methods: A 14-question REDCap survey was disseminated to 396 North American physicians who care for children with CNS tumors. Results: The response rate was 35%. Participants included radiation-oncologists (63%; 85/135) and pediatric oncologists/neuro-oncologists (37%; 50/135). Most physicians (62%) treated 1 to 5 DIPG patients per year, with 10% treating more than 10 patients per year. Reirradiation was considered a treatment option by 88% of respondents. Progressive disease and worsening clinical status were the most common reasons to consider reirradiation. The majority (84%) surveyed considered reirradiation a minimum of 6 months following initial RT. Doses varied, with median total dose of 2400 cGy (range, 1200-6000 cGy) and fraction size of 200 cGy (range, 100-900 cGy). Concurrent use of systemic agents with reirradiation was considered in 46%, including targeted agents (37%), biologics (36%), or immunotherapy (25%). One-time reirradiation was the most common practice (71%). Conclusion: Although the vast majority of physicians consider reirradiation as a treatment for DIPG, total doses and fractionation varied. Further clinical trials are needed to determine the optimal radiation dose and fractionation for reirradiation in children with progressive DIPG
Risk of first and recurrent stroke in childhood cancer survivors treated with cranial and cervical radiation therapy.
PurposeTo assess, in a retrospective cohort study, rates and predictors of first and recurrent stroke in patients treated with cranial irradiation (CRT) and/or cervical irradiation at ≤18 years of age.Methods and materialsWe performed chart abstraction (n=383) and phone interviews (n=104) to measure first and recurrent stroke in 383 patients who received CRT and/or cervical radiation at a single institution between 1980 and 2009. Stroke was defined as a physician diagnosis and symptoms consistent with stroke. Incidence of first stroke was number of first strokes per person-years of observation after radiation. We used survival analysis techniques to determine cumulative incidence of first and recurrent stroke.ResultsAmong 325 subjects with sufficient follow-up data, we identified 19 first strokes (13 ischemic, 4 hemorrhagic, 2 unknown subtype) occurring at a median age of 24 years (interquartile range 17-33 years) in patients treated with CRT. Imaging was reviewed when available (n=13), and the stroke was confirmed in 12. Overall rate of first stroke was 625 (95% confidence interval [CI] 378-977) per 100,000 person-years. The cumulative incidence of first stroke was 2% (95% CI 0.01%-5.3%) at 5 years and 4% (95% CI 2.0%-8.4%) at 10 years after irradiation. With each 100-cGy increase in the radiation dose, the stroke hazard increased by 5% (hazard ratio 1.05; 95% CI 1.01-1.09; P=.02). We identified 6 recurrent strokes; 5 had available imaging that confirmed the stroke. Median time to recurrence was 15 months (interquartile range 6 months-3.2 years) after first stroke. The cumulative incidence of recurrent stroke was 38% (95% CI 17%-69%) at 5 years and 59% (95% CI 27%-92%) at 10 years after first stroke.ConclusionCranial irradiation puts childhood cancer survivors at high risk of both first and recurrent stroke. Stroke prevention strategies for these survivors are needed
Rates and characteristics of radiographically detected intracerebral cavernous malformations after cranial radiation therapy in pediatric cancer patients.
Rates and characteristics of intracerebral cavernous malformations after cranial radiation therapy remain poorly understood. Herein we report on intracerebral cavernous malformations detected on follow-up imaging in pediatric cancer patients who received cranial radiation therapy at age ≤18 years from 1980 to 2009. Through chart reviews (n = 362) and phone interviews (n = 104) of a retrospective cohort, we identified 10 patients with intracerebral cavernous malformations. The median latency time for detection of intracerebral cavernous malformations after cranial radiation therapy was 12 years (range 1-24 years) at a median age of 21.4 years (interquartile range = 15-28). The cumulative incidence was 3% (95% confidence interval 1%-8%) at 10 years post cranial radiation therapy and 14% (95% confidence interval 7%-26%) at 15 years. Three patients underwent surgical resection. Two surgical specimens were pathologically similar to sporadically occurring intracerebral cavernous malformations; one was consistent with capillary telangiectasia. Intracerebral cavernous malformations are common after cranial radiation therapy and can show a spectrum of histologic features
Clinical Outcomes of Intraoperative Radiation Therapy for Extremity Sarcomas
Purpose. Radiation of extremity lesions, a key component of limb-sparing therapy, presents particular challenges, with significant risks of toxicities. We sought to explore the efficacy of intraoperative radiation therapy (IORT) in the treatment of soft tissue sarcomas of the extremities. Patients. Between 1995 and 2001, 17 patients received IORT for soft tissue sarcomas of the extremities. Indications for IORT included recurrent tumors in a previously radiated field or tumors adjacent to critical structures. Results. Gross total resections were achieved in all 17 patients. Two patients experienced locoregional relapses, six patients recurred at metastatic sites, and one patient died without recurrence. Thirty-six month estimates for locoregional control, disease free survival, and overall survival were 86%, 50%, and 78%, respectively. IORT was extremely well tolerated, with no toxicities referable to IORT. Conclusions. For patients with soft tissue sarcomas of the extremities, IORT used as a boost to EBRT provides excellent local control, with limited acute toxicities
Clinical outcomes of radiation therapy for transgender and gender-expansive people with cancer
IntroductionApproximately 1.6 million people in the US identify as transgender, many of whom undergo gender-affirming medical or surgical therapies. While transgender individuals are diagnosed with cancer at similar rates as those who are cisgender, the impacts of radiation therapy on outcomes of gender-affirming care in transgender, nonbinary, and gender-expansive people with cancer are understudied. We report on the experiences and outcomes of transgender and gender-expansive patients receiving radiation therapy for cancer treatment.MethodsThis study is a multi-institutional retrospective review of patients evaluated from 2005-2019 identified as transgender or gender-expansive in the medical record and treated with radiation therapy.ResultsWe identified 23 patients who received radiation to 32 sites, including 12 (38%) to the brain, head, or neck, 8 (25%) to the thorax, and 7 (22%) to the pelvis. Seventeen patients (74%) received gender-affirming hormone therapy and 13 patients (57%) underwent gender-affirming surgery. Four patients had pelvic radiation before or after gender-affirming pelvic surgery, including two trans women who had pelvic radiation after vaginoplasty. Four patients had radiation to the chest or thorax and gender-affirming chest or breast surgery, including two trans men with breast cancer. Two pediatric patients developed hypopituitarism and hypogonadism secondary to radiation therapy and, as adults, changed their hormone replacement therapy to affirm their transgender identities.DiscussionTransgender people with cancer undergo radiation therapy for a wide range of cancers. Understanding their prior gender-affirming medical or surgical treatments and future gender affirmation goals may identify important considerations for their oncologic care
Presence of cerebral microbleeds is associated with worse executive function in pediatric brain tumor survivors.
BackgroundA specific form of small-vessel vasculopathy-cerebral microbleeds (CMBs)-has been linked to various types of dementia in adults. We assessed the incidence of CMBs and their association with neurocognitive function in pediatric brain tumor survivors.MethodsIn a multi-institutional cohort of 149 pediatric brain tumor patients who received cranial radiation therapy (CRT) between 1987 and 2014 at age <21 years and 16 patients who did not receive CRT, we determined the presence of CMBs on brain MRIs. Neurocognitive function was assessed using a computerized testing program (CogState). We used survival analysis to determine cumulative incidence of CMBs and Poisson regression to examine risk factors for CMBs. Linear regression models were used to assess effect of CMBs on neurocognitive function.ResultsThe cumulative incidence of CMBs was 48.8% (95% CI: 38.3-60.5) at 5 years. Children who had whole brain irradiation developed CMBs at a rate 4 times greater than those treated with focal irradiation (P < .001). In multivariable analysis, children with CMBs performed worse on the Groton Maze Learning test (GML) compared with those without CMBs (Z-score -1.9; 95% CI: -2.7, -1.1; P < .001), indicating worse executive function when CMBs are present. CMBs in the frontal lobe were associated with worse performance on the GML (Z-score -2.4; 95% CI: -2.9, -1.8; P < .001). Presence of CMBs in the temporal lobes affected verbal memory (Z-score -2.0; 95% CI: -3.3, -0.7; P = .005).ConclusionCMBs are common and associated with neurocognitive dysfunction in pediatric brain tumor survivors treated with radiation
Clinical outcome and prognostic factors for central neurocytoma: twenty year institutional experience
Central neurocytomas are uncommon intraventricular neoplasms whose optimal management remains controversial due to their rarity. We assessed outcomes for a historical cohort of neurocytoma patients and evaluated effects of tumor atypia, size, resection extent, and adjuvant radiotherapy. Progression-free survival (PFS) was measured by Kaplan-Meier and Cox proportional hazards methods. A total of 28 patients (15 males, 13 females) were treated between 1995 and 2014, with a median age at diagnosis of 26 years (range 5-61). Median follow-up was 62.2 months and 3 patients were lost to follow-up postoperatively. Thirteen patients experienced recurrent/progressive disease and 2-year PFS was 75% (95% CI 53-88%). Two-year PFS was 48% for MIB-1 labeling >4% versus 90% for ≤4% (HR 5.4, CI 2.2-27.8, p = 0.0026). Nine patients (32%) had gross total resections (GTR) and 19 (68%) had subtotal resections (STR). PFS for >80% resection was 83 versus 67% for ≤80% resection (HR 0.67, CI 0.23-2.0, p = 0.47). Three STR patients (16%) received adjuvant radiation which significantly improved overall PFS (p = 0.049). Estimated 5-year PFS was 67% for STR with radiotherapy versus 53% for STR without radiotherapy. Salvage therapy regimens were diverse and resulted in stable disease for 54% of patients and additional progression for 38 %. Two patients with neuropathology-confirmed atypical neurocytomas died at 4.3 and 113.4 months after initial surgery. For central neurocytomas, MIB-1 labeling index >4% is predictive of poorer outcome and our data suggest that adjuvant radiotherapy after STR may improve PFS. Most patients requiring salvage therapy will be stabilized and multiple modalities can be effectively utilized
Phase II TPDCV protocol for pediatric low-grade hypothalamic/chiasmatic gliomas: 15-year update
To report long-term results for children with low-grade hypothalamic/chiasmatic gliomas treated on a phase II chemotherapy protocol. Between 1984 and 1992, 33 children with hypothalamic/chiasmatic LGGs received TPDCV chemotherapy on a phase II prospective trial. Median age was 3.0 years (range 0.3–16.2). Twelve patients (36%) underwent STRs, 14 (42%) biopsy only, and seven (21%) no surgery. Twenty patients (61%) had pathologic JPAs, nine (27%) grade II gliomas, and four (12%) no surgical sampling. Median f/u for surviving patients was 15.2 years (range 5.3–20.7); 20 of the 23 surviving patients had 14 or more years of follow-up. Fifteen-year PFS and OS were 23.4 and 71.2%, respectively. Twenty-five patients progressed, of whom 13 are NED, two are AWD, and 10 have died. All children who died were diagnosed and first treated at age three or younger. Age at diagnosis was significantly associated with relapse and survival (P = 0.004 for PFS and P = 0.037 for OS). No PFS or OS benefit was seen with STR versus biopsy/no sampling (P = 0.58 for PFS, P = 0.59 for OS). For patients with JPAs and WHO grade II tumors, the 15-year PFS was 18.8 and 22.2% (P = 0.95) and 15-year OS was 73.7 and 55.6% (P = 0.17), respectively. Upfront TPDCV for children with hypothalamic/chiasmatic LGGs resulted in 15-year OS of 71.2% and 15-year PFS of 23.4%. No survival benefit is demonstrated for greater extent of resection. Age is a significant prognostic factor for progression and survival
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