Mental health disorders are more common in patients with Hodgkin lymphoma and may negatively impact overall survival.

BACKGROUND: Long-term mental health outcomes were characterized in patients who were diagnosed with Hodgkin lymphoma (HL), and risk factors for the development of mental health disorders were identified. METHODS: Patients who were diagnosed with HL between 1997 and 2014 were identified in the Utah Cancer Registry. Each patient was matched with up to five individuals from a general population cohort identified within the Utah Population Database, a unique source of linked records that includes patient and demographic data. RESULTS: In total, 795 patients who had HL were matched with 3575 individuals from the general population. Compared with the general population, patients who had HL had a higher risk of any mental health diagnosis (hazard ratio, 1.77; 95% confidence interval, 1.57-2.00). Patients with HL had higher risks of anxiety, depression, substance-related disorders, and suicide and intentional self-inflicted injuries compared with the general population. The main risk factor associated with an increased risk of being diagnosed with mental health disorders was undergoing hematopoietic stem cell transplantation, with a hazard ratio of 2.06 (95% confidence interval, 1.53-2.76). The diagnosis of any mental health disorder among patients with HL was associated with a detrimental impact on overall survival; the 10-year overall survival rate was 70% in patients who had a mental health diagnosis compared with 86% in those patients without a mental health diagnosis (p < .0001). CONCLUSIONS: Patients who had HL had an increased risk of various mental health disorders compared with a matched general population. The current data illustrate the importance of attention to mental health in HL survivorship, particularly for patients who undergo therapy with hematopoietic stem cell transplantation.

Factors Associated with Nodal Pathologic Complete Response Among Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: Results of CALGB 40601 (HER2+) and 40603 (Triple-Negative) (Alliance).

BACKGROUND: De-escalation of axillary surgery after neoadjuvant chemotherapy (NAC) requires careful patient selection. We seek to determine predictors of nodal pathologic complete response (ypN0) among patients treated on CALGB 40601 or 40603, which tested NAC regimens in HER2+ and triple-negative breast cancer (TNBC), respectively. PATIENTS AND METHODS: A total of 760 patients with stage II-III HER2+ or TNBC were analyzed. Those who had axillary surgery before NAC (N = 122), or who had missing pretreatment clinical nodal status (cN) (N = 58) or ypN status (N = 41) were excluded. The proportion of patients with ypN0 disease was estimated for those with and without breast pathologic complete response (pCR) according to pretreatment nodal status. RESULTS: In 539 patients, the overall ypN0 rate was 76.3% (411/539) to 93.2% (245/263) in patients with breast pCR and 60.1% (166/276) with residual breast disease (RD) (P < 0.0001). For patients who were cN0 pretreatment, the ypN0 rate was 88.8% (214/241), 96.3% (104/108) with breast pCR, and 82.7% (110/133) with RD. For patients who were cN1, 66.2% (157/237) converted to ypN0, 91.7% (111/121) with breast pCR and 39.7% (46/116) with RD. For patients who were cN2/3, 65.6% (40/61) converted to ypN0, 88.2% (30/34) with breast pCR and 37.0% (10/27) with RD. On multivariable analysis, only pretreatment clinical nodal status and breast pCR/RD were associated with ypN0 status (both P < 0.0001). CONCLUSIONS: Breast pCR and pretreatment nodal status are predictive of ypN0 axillary nodal involvement, with < 5% residual nodal disease among cN0 patients who experience breast pCR. These findings support the incorporation of axillary surgery de-escalation strategies into NAC trials.

The use and efficacy of chemotherapy and radiotherapy in children and adults with pilocytic astrocytoma.

PURPOSE: The aim of this study was to understand the use of chemotherapy (CMT) and radiotherapy (RT) in pilocytic astrocytoma (PA) and their impact on overall survival (OS). METHODS: Data from the National Cancer Database (NCDB) for patients with non-metastatic WHO grade I PA from 2004 to 2014 were analyzed. Pearson's chi-squared test and multivariate logistic regression analyses were performed to assess the distribution of demographic, clinical, and treatment factors. Inverse probability of treatment weighting (IPTW) was used to account for differences in baseline characteristics. Kaplan-Meier analyses and doubly-robust estimation with multivariate Cox proportional hazards modeling were used to analyze OS. RESULTS: Of 3865 patients analyzed, 294 received CMT (7.6%), 233 received RT (6.0%), and 42 (1.1%) received both. On multivariate analyses, decreasing extent of surgical resection was associated with receipt of both CMT and RT. Brainstem tumors were associated with RT, optic nerve tumors were associated with CMT. Cerebellar tumors were inversely associated with both CMT and RT. Younger age was associated with receipt of CMT; conversely, older age was associated with receipt of RT. After IPTW, receipt of CMT and/or RT were associated with an OS decrement compared with matched patients treated with surgery alone or observation (HR 3.29, p < 0.01). CONCLUSIONS: This is the largest study to date to examine patterns of care and resultant OS outcomes in PA. We identified patient characteristics associated with receipt of CMT and RT. After propensity score matching, receipt of CMT and/or RT was associated with decreased OS.

Acute lymphoblastic leukemia.

The survival of patients with acute lymphoblastic leukemia (ALL) has improved significantly with the use of intensive multimodality treatment regimens including chemotherapy, high-dose chemotherapy and stem cell rescue, and radiation therapy when indicated. This report summarizes the treatment strategies, especially radiation therapy in the Children's Oncology Group for children with ALL. Currently, radiation therapy is only indicated for children with high-risk CNS involvement at diagnosis or relapse, testicular relapse and as part of the conditioning regimen for hematopoietic stem cell transplantation. Future research strategies regarding the indications for and dosages of radiation therapy and novel radiation techniques are discussed.

The radiation dose-response of non-retroperitoneal soft tissue sarcoma with positive margins: An NCDB analysis.

OBJECTIVES: Positive margins can increase the risk of local recurrence of soft tissue sarcomas (STS). Utilizing a national registry, we investigated patterns of care and overall survival (OS) of patients with margin-positive non-retroperitoneal STS who received preoperative radiation therapy, adjuvant radiation therapy, or both. METHODS: Adult patients with non-retroperitoneal STS who underwent resection and RT from 2004 to 2015 were included. Kaplan-Meier, log-rank analysis, and Cox regression analysis were performed. RESULTS: We identified 5726 patients. Most had a tumor size >5 cm (60%), grade 3 disease (67%), and microscopically positive margins (57%). Compared to ≤50.4 Gy, a dose of 66 to 69.99 Gy was associated with decreased risk of death on multivariate analysis (HR 0.69, 95%; CI, 0.50-0.94). Receipt of a boost was associated with decreased risk of death on univariate analysis (HR 0.54, 95%; CI, 0.29-0.99). In patients with grade 2 to 3 tumors without the gross disease, there was an OS benefit associated with a boost on multivariate analysis (HR 0.39, 95%; CI, 0.16-0.97). CONCLUSION: This analysis appears to show an OS benefit of dose escalation to 66 to 69 Gy for margin-positive non-retroperitoneal STS. A Postoperative boost is associated with higher OS in grade 2 to 3 STS without the gross disease.

The value of high-dose radiotherapy in intracranial ependymoma.

BACKGROUND: We sought to evaluate the impact of adjuvant radiotherapy dose on overall survival (OS) after surgical resection for localized intracranial ependymoma. PROCEDURE: The National Cancer Database (NCDB) was queried from 2004 to 2015 for patients of all ages with intracranial WHO grade II to III ependymoma treated with surgery and 4500 to 7000 cGy of adjuvant radiotherapy. Pearson χ2 test and multivariate logistic regression analyses were used to assess clinicodemographic factors and patterns of care. After propensity-score matching, OS was assessed with Kaplan-Meier analyses and doubly robust estimation with multivariate Cox proportional hazards modeling. RESULTS: Of the 1153 patients meeting criteria, 529 (46%) received ≤ 5400 cGy and 624 (54%) received > 5400 cGy. At a median follow-up of 54.5 months, an OS benefit was observed for > 5400 cGy in pediatric patients aged 2-18 years (hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.28-0.99, P = 0.047). No OS difference was found between ≤ 5400 cGy and > 5400 cGy in pediatric patients aged < 2 years (P = 0.819) or in adults (P = 0.180). Increasing age, WHO grade III, subtotal resection, and receipt of chemotherapy portended worse OS. Age 2 to 18 years, WHO III grade, supratentorial location, and receipt of chemotherapy were associated with receiving > 5400 cGy. CONCLUSION: Adjuvant radiotherapy dose > 5400 cGy was associated with improved OS for children aged 2-18 years with WHO grade II-III intracranial ependymoma. No OS benefit was found with > 5400 cGy in adults or children less than two years of age.

Is radiation indicated for young women with early stage, node-negative breast cancer after mastectomy? A multi-institution, retrospective review.

The role of post-mastectomy radiation for women with node negative, early stage disease is not well-defined. The purpose of this study is to more clearly define a subset of women who are ≤40 years of age with T1-T2, node negative breast cancer who may benefit from post-mastectomy radiation. Using tumor registries at two institutions, we identified 219 women ≤40 years of age with T1-T2, node negative breast cancer treated with mastectomy. Of these 219 patients, 38 received post-mastectomy radiation and 181 did not. Kaplan-Meier methods and cox proportional-hazards regression models were employed for statistical analysis. There were no locoregional failures in the women receiving post mastectomy radiation, which lead to a nonsignificant increase in freedom from locoregional recurrence (P=.08). For women not receiving post-mastectomy radiation, freedom from locoregional recurrence was 94.7% and 89.7% at 5- and 10-years. Lymphovascular space invasion (LVSI) was the only factor predictive of locoregional recurrence. For women without LVSI, freedom from locoregional recurrence was 96.0% and 93.3% at 5- and 10-years respectively. For women with LVSI who did not receive post mastectomy radiation, freedom from locoregional recurrence was 89.1% at 5-years. There were no failures in the women with LVSI who received post mastectomy radiation. For women ≤40 years of age with T1-2, node negative breast cancer treated with mastectomy and no post-mastectomy radiation, locoregional control is excellent in the absence of LVSI, regardless of other risk factors. In the presence of LVSI (regardless of other risk factors), the risk of locoregional recurrence is high and appears to be decreased with post-mastectomy radiation.

Disparities in care for elderly women with endometrial cancer adversely effects survival.

PURPOSE: Elderly women with endometrial cancer are at increased risk of local recurrence and cancer-specific death compared to younger women. We sought to investigate adjuvant radiotherapy (RT) practice patterns and effects on survival in elderly women with endometrial cancer. METHODS: Women from the National Cancer Data Base (NCDB) with FIGO IA grade 3 to FIGO IVA endometrial cancer diagnosed from 2004-2013 were included. Chi square analysis was used to compare the elderly (80+) and non-elderly women (18-79) and women who received RT and those that did not. Univariate and multivariate logistic regression were used to determine predictors of receipt of oncologic surgery and adjuvant RT. Univariate and multivariate Cox survival analyses were performed to examine the effect of radiotherapy on survival. Propensity score matching and shared frailty analysis were done in the elderly cohort. RESULTS: We identified 48,871 women for analysis. Rates of oncologic surgery were higher in the women 80+ compared with rates of adjuvant RT (95% versus 34%). Rates of RT receipt were higher in non-elderly women (48% versus 34%, p<0.001). Age over 80 was a negative predictive factor (OR 0.62, p<0.001) for receipt of adjuvant RT and oncologic surgery (OR 0.81, p=0.03). Adjuvant RT was associated with a decreased risk of death in elderly (HR 0.79, p<0.001) and non-elderly women (HR 0.77, p<0.001). CONCLUSION: Endometrial cancer patients over age 80 have similar rates of oncologic surgery as younger women but are significantly less likely to receive adjuvant RT, and this negatively impacts their survival.

The Addition of Adjuvant Chemotherapy to Radiation in Early-Stage High-Risk Endometrial Cancer: Survival Outcomes and Patterns of Care.

OBJECTIVE: Early-stage high-risk endometrial cancer (HREC) treated with adjuvant radiotherapy (aRT) alone has been associated with an increased risk of distant relapse. The addition of chemotherapy to radiotherapy (aCRT) may benefit overall survival (OS). We investigated the patterns-of-care and OS benefit of aCRT in HREC by analyzing a large national registry. METHODS: Our query was limited to patients with the International Federation of Gynecology and Obstetrics stage IB and II HREC with either papillary serous, clear cell, or grade 3 adenocarcinoma, diagnosed between 2004 and 2012. Logistic and Cox regression analyses were utilized to identify predictors of aCRT use and OS, respectively. Survival analysis was performed with Kaplan Meier and log-rank methods. Propensity score matching was employed to decrease the potential influence of selection bias. RESULTS: A total of 11,746 patients were identified for analysis with 8206 (69.9%) receiving aCRT, and 3540 (30.1%) received aRT. Predictors of aCRT included International Federation of Gynecology and Obstetrics stage II (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.22-1.57), papillary serous (OR, 9.44; 95% CI, 8.22-10.85) or clear cell (OR, 3.21; 95% CI, 2.59-3.97) histology, lymph nodes removed (OR, 1.48; 95% CI, 1.31-1.69), and receipt of brachytherapy alone (OR, 1.55; 95% CI, 1.36-1.78). Estimated 5-year OS was 75.2% for patients receiving aRT only and 79.2% for those receiving aCRT (P < 0.001). When compared with aRT, aCRT was associated with improved OS on multivariate (hazard ratio, 0.78; 95% CI, 0.61-0.99) analysis. A univariate shared-frailty Cox regression after propensity score matching revealed persistence of the OS benefit with aCRT (hazard ratio, 0.74; 95% CI, 0.65-0.84). CONCLUSIONS: The addition of adjuvant chemotherapy to radiation in HREC is associated with improved OS. Multiple demographic and clinical factors significantly influence the choice of adjuvant therapy in this setting.

Post-mastectomy Radiotherapy for pT3N0 Breast Cancers: A Retrospective, Multi-Institution Review.

The role of post-mastectomy radiotherapy for pT3N0 breast cancers remains undefined. The purpose of this study was to report institutional outcomes for women with pT3N0 breast cancers treated with and without post-mastectomy radiotherapy. We collected data from two large tumor registries on pT3N0 breast cancers diagnosed between 1985 and 2014. Kaplan-Meier estimates were used to analyze freedom from local-regional recurrence (FFLR), relapse free survival, and overall survival. This analysis identified 93 women with pT3N0 breast cancers. Of these, 53 received post-mastectomy radiotherapy and 40 did not. Median follow-up was 6.2 years and 5.3 years in the non-post-mastectomy radiotherapy and post-mastectomy radiotherapy cohorts, respectively. Women not undergoing post-mastectomy radiotherapy were more likely to be diagnosed in the 1980s and 1990s and were less likely to receive systemic therapies than women receiving post-mastectomy radiotherapy (p < 0.05). There was a trend toward increased FFLR in the women receiving post-mastectomy radiotherapy (p = 0.15). FFLR in the post-mastectomy radiotherapy cohort was 98% at both 5 and 10 years. For women not receiving post-mastectomy radiotherapy, FFLR was 88% at both 5 and 10 years. Women not receiving post-mastectomy radiotherapy in our study had an isolated local-regional failure rate of 12% at 10 years, despite receiving inferior systemic treatment by current standards. Local-regional control after post-mastectomy radiotherapy for pT3N0 breast cancers was excellent. Further research is needed to define post-mastectomy radiotherapy indications for this patient population when receiving chemotherapy and endocrine therapy in line with current guidelines.

Chemoradiation versus chemotherapy or radiation alone in stage III endometrial cancer: Patterns of care and impact on overall survival.

PURPOSE: We aimed to investigate the patterns-of-care and overall survival (OS) benefit of aCRT versus adjuvant monotherapy (aMT), defined as either chemotherapy or radiation alone, utilizing a large national registry of patients. PATIENTS AND METHODS: Adult patients with stage III endometrial adenocarcinoma diagnosed from 2004 to 2013 were included. Logistic and Cox regression modeling was used to identify factors predictive of receipt of aCRT and OS, respectively. Survival analysis was performed with Kaplan Meier and log-rank analysis. Propensity score matching and sensitivity analysis was performed to address selection bias and presence of potential confounding variables. RESULTS: A total of 21,027 patients were identified: 11,435 (54.4%) patients received aMT, while 9592 (45.6%) received aCRT. Utilization of aCRT increased over the study period (p<0.01). Factors predictive of receiving aCRT include private insurance (OR: 1.67, 95% CI: 1.30-2.14), Medicare (OR: 1.33, 95% CI: 1.01-1.75), FIGO stage IIIC disease (OR: 1.36, 95% CI: 1.19-1.54), lymphovascular space invasion (OR: 1.14, 95% CI: 1.03-1.27), and lymph node surgery performed (OR: 1.42, 95% CI: 1.15-1.74). Median survival in years for aCRT, RT, and CT was 10.3, 7.1, and 5.6, respectively (p<0.001). Compared to aMT, aCRT was associated with a decrease risk of death on multivariate analysis (HR: 0.62, 95% CI: 0.56-0.70). The benefit of aCRT over aMT persisted after propensity score matching. CONCLUSION: The use of aCRT for stage III endometrial cancer is increasing. Multiple clinical and demographic factors were predictive of aCRT use. When compared to chemotherapy or radiation alone, aCRT is associated with an OS benefit.

Long-term life expectancy for children with ependymoma and medulloblastoma.

OBJECTIVES: There is a paucity of long-term follow-up data for children with intracranial ependymoma (IE) and medulloblastoma (MB). What happens to these children 20, 30, or 40 years after diagnosis? Do they have potential for a normal lifespan? The purpose of this study was to ascertain the long-term survival potential in children with MB or IE who have survived 5 years from diagnosis. METHODS: A retrospective analysis was conducted using the SEER Program. Children (ages 0-19 years) from 1973 to 2011 with a diagnosis of MB or IE were identified. A cohort was created of potentially cured patients who survived 5 years from diagnosis. Cox proportional hazards models and Kaplan-Meier estimates were utilized to analyze long-term survival. RESULTS: We identified 876 patients with MB and 474 patients with IE who were alive 5 years from diagnosis. Patients with MB had a 30-year overall survival (OS) and cancer-specific survival (CSS) of 70.2% and 80.1%, respectively. Patients with IE had a 30-year OS and CSS of 57.3% and 68.8%, respectively. When comparing MB with IE, MB had improved CSS (P = 0.04) and trended toward increased OS (P = 0.10). CONCLUSIONS: A significant number of deaths due to disease occur for several decades after treatment for both IE and MB. Despite this, the potential for long-term survival exists in 5-year survivors of both histologies. If alive at 5 years from diagnosis, patients with MB tend to have a lower risk of death from disease compared to those with IE.

Primary T cell central nervous system lymphoblastic lymphoma in a child: case report and literature review.

PURPOSE: Primary central nervous system lymphoma (PCNSL) of T cell origin is rare in pediatric patients. We report a case of T cell PCNSL in a 12-year-old boy and review the literature to highlight the importance of brain biopsy to definitively establish the diagnosis when PCNSL is suspected. CASE REPORT: A 12-year-old boy presented with worsening left-sided weakness, nausea, vomiting, headache, blurred vision, and diplopia. Magnetic resonance imaging revealed right parietal gyral thickening with faint meningeal contrast enhancement. No clear diagnosis was identified after serum testing, cerebrospinal fluid analysis, and cerebral angiography. To establish the diagnosis definitively, a right craniotomy and open, frameless stereotactic biopsy were performed, which yielded the diagnosis of lymphoblastic T cell lymphoma. CONCLUSIONS: PCNSL of T cell origin in children remains poorly studied, with only 18 detailed cases reported over the last three decades, including this case. Establishing a definitive diagnosis of PCNSL is challenging, and a brain biopsy is often required to obtain enough tissue for pathological analysis. Increasing awareness and identification of children diagnosed with T cell PCNSL is needed to better understand the molecular biology of this disease and develop more standardized treatment regimens.

Partial Breast Irradiation for Patients With Early-Stage Invasive Breast Cancer or Ductal Carcinoma In Situ: An ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides evidence-based recommendations on appropriate indications and techniques for partial breast irradiation (PBI) for patients with early-stage invasive breast cancer and ductal carcinoma in situ. METHODS: ASTRO convened a task force to address 4 key questions focused on the appropriate indications and techniques for PBI as an alternative to whole breast irradiation (WBI) to result in similar rates of ipsilateral breast recurrence (IBR) and toxicity outcomes. Also addressed were aspects related to the technical delivery of PBI, including dose-fractionation regimens, target volumes, and treatment parameters for different PBI techniques. The guideline is based on a systematic review provided by the Agency for Healthcare Research and Quality. Recommendations were created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: PBI delivered using 3-dimensional conformal radiation therapy, intensity modulated radiation therapy, multicatheter brachytherapy, and single-entry brachytherapy results in similar IBR as WBI with long-term follow-up. Some patient characteristics and tumor features were underrepresented in the randomized controlled trials, making it difficult to fully define IBR risks for patients with these features. Appropriate dose-fractionation regimens, target volume delineation, and treatment planning parameters for delivery of PBI are outlined. Intraoperative radiation therapy alone is associated with a higher IBR rate compared with WBI. A daily or every-other-day external beam PBI regimen is preferred over twice-daily regimens due to late toxicity concerns. CONCLUSIONS: Based on published data, the ASTRO task force has proposed recommendations to inform best clinical practices on the use of PBI.

Kidney Disease in Childhood Cancer Survivors Treated With Radiation Therapy: A Comprehensive PENTEC Genitourinary Review.

PURPOSE: Kidney injury is a known late and potentially devastating complication of abdominal radiation therapy (RT) in pediatric patients. A comprehensive Pediatric Normal Tissue Effects in the Clinic review by the Genitourinary (GU) Task Force aimed to describe RT dose-volume relationships for GU dysfunction, including kidney, bladder, and hypertension, for pediatric malignancies. The effect of chemotherapy was also considered. METHODS AND MATERIALS: We conducted a comprehensive PubMed search of peer-reviewed manuscripts published from 1990 to 2017 for investigations on RT-associated GU toxicities in children treated for cancer. We retrieved 3271 articles with 100 fulfilling criteria for full review, 24 with RT dose data and 13 adequate for modeling. Endpoints were heterogenous and grouped according to National Kidney Foundation: grade ≥1, grade ≥2, and grade ≥3. We modeled whole kidney exposure from total body irradiation (TBI) for hematopoietic stem cell transplant and whole abdominal irradiation (WAI) for patients with Wilms tumor. Partial kidney tolerance was modeled from a single publication from 2021 after the comprehensive review revealed no usable partial kidney data. Inadequate data existed for analysis of bladder RT-associated toxicities. RESULTS: The 13 reports with long-term GU outcomes suitable for modeling included 4 on WAI for Wilms tumor, 8 on TBI, and 1 for partial renal RT exposure. These reports evaluated a total of 1191 pediatric patients, including: WAI 86, TBI 666, and 439 partial kidney. The age range at the time of RT was 1 month to 18 years with medians of 2 to 11 years in the various reports. In our whole kidney analysis we were unable to include chemotherapy because of the heterogeneity of regimens and paucity of data. Age-specific toxicity data were also unavailable. Wilms studies occurred from 1968 to 2011 with mean follow-ups 8 to 15 years. TBI studies occurred from 1969 to 2004 with mean follow-ups of 4 months to 16 years. We modeled risk of dysfunction by RT dose and grade of toxicity. Normal tissue complication rates ≥5%, expressed as equivalent doses, 2 Gy/fx for whole kidney exposures occurred at 8.5, 10.2, and 14.5 Gy for National Kidney Foundation grades ≥1, ≥2, and ≥3, respectively. Conventional Wilms WAI of 10.5 Gy in 6 fx had risks of ≥grade 2 toxicity 4% and ≥grade 3 toxicity 1%. For fractionated 12 Gy TBI, those risks were 8% and <3%, respectively. Data did not support whole kidney modeling with chemotherapy. Partial kidney modeling from 439 survivors who received RT (median age, 7.3 years) demonstrated 5 or 10 Gy to 100% kidney gave a <5% risk of grades 3 to 5 toxicity with 1500 mg/m2 carboplatin or no chemo. With 480 mg/m2 cisplatin, a 3% risk of ≥grade 3 toxicity occurred without RT and a 5% risk when 26% kidney received ≥10 Gy. With 63 g/m2 of ifosfamide, a 5% risk of ≥grade 3 toxicity occurred with no RT, and a 10% toxicity risk occurred when 42% kidney received ≥10 Gy. CONCLUSIONS: In patients with Wilms tumor, the risk of toxicity from 10.5 Gy of WAI is low. For 12 Gy fractionated TBI with various mixtures of chemotherapy, the risk of severe toxicity is low, but low-grade toxicity is not uncommon. Partial kidney data are limited and toxicity is associated heavily with the use of nephrotoxic chemotherapeutic agents. Our efforts demonstrate the need for improved data gathering, systematic follow-up, and reporting in future clinical studies. Current radiation dose used for Wilms tumor and TBI appear to be safe; however, efforts in effective kidney-sparing TBI and WAI regimens may reduce the risks of renal injury without compromising cure.

The Pediatric Proton and Photon Therapy Comparison Cohort: Study Design for a Multicenter Retrospective Cohort to Investigate Subsequent Cancers After Pediatric Radiation Therapy.

Purpose: The physical properties of protons lower doses to surrounding normal tissues compared with photons, potentially reducing acute and long-term adverse effects, including subsequent cancers. The magnitude of benefit is uncertain, however, and currently based largely on modeling studies. Despite the paucity of directly comparative data, the number of proton centers and patients are expanding exponentially. Direct studies of the potential risks and benefits are needed in children, who have the highest risk of radiation-related subsequent cancers. The Pediatric Proton and Photon Therapy Comparison Cohort aims to meet this need. Methods and Materials: We are developing a record-linkage cohort of 10,000 proton and 10,000 photon therapy patients treated from 2007 to 2022 in the United States and Canada for pediatric central nervous system tumors, sarcomas, Hodgkin lymphoma, or neuroblastoma, the pediatric tumors most frequently treated with protons. Exposure assessment will be based on state-of-the-art dosimetry facilitated by collection of electronic radiation records for all eligible patients. Subsequent cancers and mortality will be ascertained by linkage to state and provincial cancer registries in the United States and Canada, respectively. The primary analysis will examine subsequent cancer risk after proton therapy compared with photon therapy, adjusting for potential confounders and accounting for competing risks. Results: For the primary aim comparing overall subsequent cancer rates between proton and photon therapy, we estimated that with 10,000 patients in each treatment group there would be 80% power to detect a relative risk of 0.8 assuming a cumulative incidence of subsequent cancers of 2.5% by 15 years after diagnosis. To date, 9 institutions have joined the cohort and initiated data collection; additional centers will be added in the coming year(s). Conclusions: Our findings will affect clinical practice for pediatric patients with cancer by providing the first large-scale systematic comparison of the risk of subsequent cancers from proton compared with photon therapy.

Delineating the Subarachnoid Space in the Adult Lumbosacral Spine Using Computed Tomographic Myelography: An Aid for Clinical Target Volume Delineation in Craniospinal Irradiation.

Purpose: Our aim was to characterize the patterns of cerebrospinal fluid (CSF) extension in the lumbosacral spine using computed tomography (CT) myelograms to provide an evidence base for clinical target volume (CTV) definition in adults receiving craniospinal irradiation. Methods and Materials: This was a retrospective analysis of diagnostic CT lumbar myelograms performed in 30 patients between the ages of 22 and 50. Lateral extension of CSF beyond the thecal sac was measured along each lumbar and sacral nerve root to the nearest millimeter, as was the distance of inferior extension of CSF beyond the caudal end of the thecal sac. Each patient's lateral and inferior CSF extensions were mapped onto a standardized CT data set to create a model target volume in the lumbosacral spine that would contain the aggregate observed CSF distributions from the analyzed CT myelograms. The median extension distances, interquartile ranges, and 90th percentile for distance at each level were calculated. Results: The median lateral extension of CSF along nerve roots beyond the thecal sac-as measured perpendicular to the longitudinal axis-increased from 0 mm (interquartile range [IQR], 0-4 mm) at L1 to 8 mm (IQR, 6-12 mm) at S1 and 0 mm (IQR, 0-0 mm) at S4. The 90th percentile ranged from 5 to 14 mm laterally, with a pattern partially extending into the S1 and S2 sacral foramen. Median CSF extension inferior to the caudal sac was 5 mm (IQR, 2-8 mm), with 90% of patients within 12 mm. An atlas was generated to guide CTV delineation for highly conformal radiation techniques. Conclusion: These results provide information on patterns of CSF extension in the lumbosacral spine of adults and can serve as a model for CTV guidelines that balance comprehensive coverage of the CSF compartment while minimizing the dose to nontarget tissues.

Patterns of Care and Utilization Disparities in Proton Radiation Therapy for Pediatric Central Nervous System Malignancies.

Purpose: Proton radiation therapy (PR) is well established in the treatment of pediatric malignancies in the central nervous system (CNS) with dosimetric advantages that reduce late radiation therapy (RT) effects. In this analysis, we sought to evaluate the utilization of PR in children with primary CNS malignancies and characterize the clinical and sociodemographic factors predictive of receipt of PR. Methods and Materials: The National Cancer Database was queried to identify all pediatric patients with primary CNS malignancies treated with curative intent RT from 2004 to 2017. Clinical characteristics and demographics were analyzed using standard t and χ2 testing. Predictors of PR receipt were identified with univariable and multivariable logistic regression. Results: We identified 9126 patients ≤18 years of age treated with RT between 2004 and 2017, of which 1045 (11.5%) received PR. PR usage continued to increase significantly, from <1% in 2004 to 28% in 2017. The proportion of white and Asian patients receiving PR for nonhigh-grade glioma and nonmeningioma CNS malignancies during the study period rose from <1% for both to 35% and 44%, respectively, and in black patients the proportion rose from <1% to 26%. Multivariable predictors of receipt of PR include year of diagnosis, age <6 years, income level, distance from PR facility, and histology; multivariable predictors of receipt of photon RT include black race, rural residence, and Medicaid insurance. These factors remained significant when isolating the most recent 5 years of data. Conclusions: Proton radiation therapy usage for CNS malignancies increased significantly during the study period. Despite the potential clinical advantages of PR for pediatric primary CNS malignancies, there are notable socioeconomic, geographic, and racial disparities in the receipt of PR that persisted despite the increased availability and accessibility. Further study is warranted to identify how to address the disparities and better support these patients.

Radiation therapy and secondary malignancy in Li-Fraumeni syndrome: A hereditary cancer registry study.

BACKGROUND: Li-Fraumeni Syndrome (LFS) is a rare cancer-predisposing condition caused by germline mutations in TP53. Conventional wisdom and prior work has implied an increased risk of secondary malignancy in LFS patients treated with radiation therapy (RT); however, this risk is not well-characterized. Here we describe the risk of subsequent malignancy and cancer-related death in LFS patients after undergoing RT for a first or second primary cancer. METHODS: We reviewed a multi-institutional hereditary cancer registry of patients with germline TP53 mutations who were treated from 2004 to 2017. We assessed the rate of subsequent malignancy and death in the patients who received RT (RT group) as part of their cancer treatment compared to those who did not (non-RT group). RESULTS: Forty patients with LFS were identified and 14 received RT with curative intent as part of their cancer treatment. The median time to follow-up after RT was 4.5 years. Fifty percent (7/14) of patients in the curative-intent group developed a subsequent malignancy (median time 3.5 years) compared to 46% of patients in the non-RT group (median time 5.0 years). Four of seven subsequent malignancies occurred within a prior radiation field and all shared histology with the primary cancer suggesting recurrence rather than new malignancy. CONCLUSION: We found that four of14 patients treated with RT developed in-field malignancies. All had the same histology as the primary suggesting local recurrences rather than RT-induced malignancies. We recommend that RT should be considered as part of the treatment algorithm when clinically indicated and after multidisciplinary discussion.