Prognostic value of cerebrospinal fluid tumor cell count in leptomeningeal disease from solid tumors.

PURPOSE: Treatment decisions for leptomeningeal disease (LMD) rely on patient risk stratification, since clinicians lack objective prognostic tools. The introduction of rare cell capture technology for identification of cerebrospinal fluid tumor cells (CSF-TCs), such as CNSide assay, improved the sensitivity of LMD diagnosis, but prognostic value is unknown. This study assesses the prognostic value of CSF-TC density in patients with LMD from solid tumors. METHODS: We conducted a retrospective cohort study of patients with newly diagnosed or previously treated LMD from a single institution who had CNSide assay testing for CSF-TCs from 2020 to 2023. Univariable and multivariable survival analyses were conducted with Cox proportional-hazards modeling. Maximally-selected rank statistics were used to determine an optimal cutpoint for CSF-TC density and survival. RESULTS: Of 31 patients, 29 had CSF-TCs detected on CNSide. Median (interquartile range [IQR]) CSF-TC density was 67.8 (4.7-639) TCs/mL. CSF cytology was positive in 16 of 29 patients with positive CNSide (CNSide diagnostic sensitivity = 93.5%, negative predictive value = 85.7%). Median (IQR) survival from time of CSF-TC detection was 176 (89-481) days. On univariable and multivariable analysis, CSF-TC density was significantly associated with survival. An optimal cutpoint for dichotomizing survival by CSF-TC density was 19.34 TCs/mL. The time-dependent sensitivity and specificity for survival using this stratification were 76% and 67% at 6 months and 65% and 67% at 1 year, respectively. CONCLUSIONS: CSF-TC density may carry prognostic value in patients with LMD from solid tumors. Integrating CSF-TC density into LMD patient risk-stratification may help guide treatment decisions.

Craniospinal irradiation for CNS leukemia: rates of response and durability of CNS control.

PURPOSE: Management of CNS involvement in leukemia may include craniospinal irradiation (CSI), though data on CSI efficacy are limited. METHODS: We retrospectively reviewed leukemia patients who underwent CSI at our institution between 2009 and 2021 for CNS involvement. CNS local recurrence (CNS-LR), any recurrence, progression-free survival (PFS), CNS PFS, and overall survival (OS) were estimated. RESULTS: Of thirty-nine eligible patients treated with CSI, most were male (59%) and treated as young adults (median 31 years). The median dose was 18 Gy to the brain and 12 Gy to the spine. Twenty-five (64%) patients received CSI immediately prior to allogeneic hematopoietic cell transplant, of which 21 (84%) underwent total body irradiation conditioning (median 12 Gy). Among 15 patients with CSF-positive disease immediately prior to CSI, all 14 assessed patients had pathologic clearance of blasts (CNS-response rate 100%) at a median of 23 days from CSI start. With a median follow-up of 48 months among survivors, 2-year PFS and OS were 32% (95% CI 18-48%) and 43% (95% CI 27-58%), respectively. Only 5 CNS relapses were noted (2-year CNS-LR 14% (95% CI 5-28%)), which occurred either concurrently or after a systemic relapse. Only systemic relapse after CSI was associated with higher risk of CNS-LR on univariate analysis. No grade 3 or higher acute toxicity was seen during CSI. CONCLUSION: CSI is a well-tolerated and effective treatment option for patients with CNS leukemia. Control of systemic disease after CSI may be important for CNS local control. CNS recurrence may reflect reseeding from the systemic space.

Increased risk of recurrence and disease-specific death following delayed postoperative radiation for Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is often treated with surgery and postoperative radiation therapy (PORT). The optimal time to initiate PORT (Time-to-PORT [ttPORT]) is unknown. PURPOSE: We assessed if delays in ttPORT were associated with inferior outcomes. METHODS: Competing risk regression was used to evaluate associations between ttPORT and locoregional recurrence (LRR) for patients with stage I/II MCC in a prospective registry and adjust for covariates. Distant metastasis and death were competing risks. RESULTS: The cohort included 124 patients with median ttPORT of 41 days (range: 8-125 days). Median follow-up was 55 months. 17 (14%) patients experienced a LRR, 14 (82%) of which arose outside the radiation field. LRR at 5 years was increased for ttPORT >8 weeks vs ≤ 8 weeks, 28.0% vs 9.2%, P = .006. There was an increase in the cumulative incidence of MCC-specific death with increasing ttPORT (HR = 1.14 per 1-week increase, P = .016). LIMITATIONS: The relatively low number of LRRs limited the extent of our multivariable analyses. CONCLUSIONS: Delay of PORT was associated with increased LRR, usually beyond the radiation field. This is consistent with the tendency of MCC to spread quickly via lymphatics. Initiation of PORT within 8 weeks was associated with improved locoregional control and MCC-specific survival.

Assessment of Lymphoma and Other Hematologic Malignancies Training Needs Among Radiation Oncology Residents: a Brief Report.

The role of radiation therapy (RT) varies across hematologic malignancies (HM). Radiation oncology (RO) resident comfort with specific aspects of HM patient management is unknown. The International Lymphoma RO Group (ILROG) assessed resident HM training opportunities and interest in an HM away elective. RO residents (PGY2-5) in the Association of Residents in RO (ARRO) database (n = 572) were emailed an anonymous, web-based survey in January 2019 including binary, Likert-type scale (1 = not at all, 5 = extremely, reported as median [interquartile range]), and multiple-choice questions. Of 134 resident respondents (23%), 86 (64%) were PGY4/5 residents and 36 (27%) were in larger programs (≥ 13 residents). Residents reported having specialized HM faculty (112, 84%) and a dedicated HM rotation (95, 71%). Residents reported "moderate" preparedness to advocate for RT in multidisciplinary conferences (3 [2-3]); make HM-related clinical decisions (3 [2-4]); and critique treatment planning (3 [2-4]). They reported feeling "moderately" to "quite" prepared to contour HM cases (3.5 [3-4]) and "quite" prepared to utilize the PET-CT five-point scale (4 [3-5]). Overall, residents reported feeling "moderately" prepared to treat HM patients (3 [2-3]); 24 residents (23%) felt "quite" or "extremely" prepared. Sixty-six residents (49%) were potentially interested in an HM away elective, commonly to increase comfort with treating HM patients (65%). Therefore, HM training is an important component of RO residency, yet a minority of surveyed trainees felt quite or extremely well prepared to treat HM patients. Programs should explore alternative and additional educational opportunities to increase resident comfort with treating HM patients.

Effect of total body irradiation lung block parameters on lung doses using three-dimensional dosimetry.

PURPOSE: Total body irradiation (TBI) is an integral part of stem cell transplant. However, patients are at risk of treatment-related toxicities, including radiation pneumonitis. While lung dose is one of the most crucial aspects of TBI dosimetry, currently available data are based on point doses. As volumetric dose distribution could be substantially altered by lung block parameters, we used 3D dosimetry in our treatment planning system to estimate volumetric lung dose and measure the impact of various lung block designs. MATERIALS AND METHODS: We commissioned a TBI beam model in RayStation that matches the measured tissue-phantom ratio under our clinical TBI setup. Cerrobend blocks were automatically generated in RayStation on thoracic Computed Tomography (CT) scans from three anonymized patients using the lung, clavicle, spine, and diaphragmatic contours. The margin for block edge was varied to 0, 1, or 2 cm from the superior, lateral, and inferior thoracic borders, with a uniform margin 2.5 cm lateral to the vertebral bodies. The lung dose was calculated and compared with a prescription dose of 1200 cGy in six fractions (three with blocks and three without). RESULT: The point dose at midplane under the block and the average lung dose are at the range of 73%-76% and 80%-88% of prescription dose respectively regardless of the block margins. In contrast, the percent lung volume receiving 10 Gy increased by nearly two-fold, from 31% to 60% over the margins from 0 to 2 cm. CONCLUSIONS: The TPS-derived 3D lung dose is substantially different from the nominal dose assumed with HVL lung blocks. Point doses under the block are insufficient to accurately gauge the relationship between dose and pneumonitis, and TBI dosimetry could be highly variable between patients and institutions as more descriptive parameters are not included in protocols. Much progress remains to be made to optimize and standardize technical aspects of TBI, and better dosimetry could provide more precise dosimetric predictors for pneumonitis risk.

Radiation-induced brain injury in patients with meningioma treated with proton or photon therapy.

INTRODUCTION: Radiation therapy is often used to treat meningioma with adverse features or when unresectable. Proton therapy has advantages over photon therapy in reducing integral dose to the brain. This study compared the incidence of radiological and clinical adverse events after photon versus proton therapy in the treatment of meningioma. METHODS: A retrospective review was conducted on patients with meningioma treated with proton or photon therapy at two high-volume tertiary cancer centers. Patients with a history of prior radiation therapy (RT) or less than 3 months of follow-up were excluded. Post-RT imaging changes were categorized into abnormal T2 signal intensities (T2 changes) or abnormal T1 post-contrast and T2 signal intensities (T1c+T2 changes) on magnetic resonance imaging (MRI). Clinical outcomes of adverse events and survival were compared between the proton and photon therapies. RESULTS: Among the total of 77 patients, 38 patients received proton therapy and 39 patients received photon therapy. The median age at diagnosis was 55 years and median follow-up was 2.2 years. No significant differences in symptomatic adverse events were observed between the two groups: grade ≥ 2 adverse events were seen in 4 (10.5%) patients in the proton group and 3 (7.7%) patients in the photon group (p = 0.67). The 2-year cumulative incidences of T2 changes were 38.3% after proton therapy and 47.7% after photon therapy (p = 0.53) and the 2-year cumulative incidences of T1c+T2 changes were 26.8% after proton therapy and 5.3% after photon therapy (p = 0.02). One patient experienced grade ≥ 4 adverse event in each group (p = 0.99). Estimated 2-year progression-free survival was 79.5% (proton therapy 76.0% vs. photon therapy 81.3%, p = 0.66) and 2-year overall survival was 89.7% (proton therapy 86.6% vs. photon therapy 89.3%, p = 0.65). CONCLUSIONS: Following RT, high rates of T2 changes were seen in meningioma patients regardless of treatment modality. Proton therapy was associated with significantly higher rates of T1c+T2 changes compared with photon therapy, but severe adverse events were uncommon in both groups and survival outcomes were comparable between the two groups. Future studies will aim at correlating the MRI changes with models that can be incorporated into RT planning to avoid toxicity.

Total Body Irradiation Is Safe and Similarly Effective as Chemotherapy-Only Conditioning in Autologous Stem Cell Transplantation for Mantle Cell Lymphoma.

Autologous stem cell transplant (ASCT) consolidation has become a standard approach for patients with mantle cell lymphoma (MCL), yet there is little consensus on the role of total body irradiation (TBI) as part of high-dose transplantation conditioning. We analyzed 75 consecutive patients with MCL who underwent ASCT at our institution between 2001 and 2011 with either TBI-based (n = 43) or carmustine, etoposide, cytarabine, melphalan (BEAM; n = 32) high-dose conditioning. Most patients (97%) had chemosensitive disease and underwent transplantation in first remission (89%). On univariate analysis, TBI conditioning was associated with a trend toward improved PFS (hazard ratio [HR], .53; 95% confidence interval [CI], .28-1.00; P = .052) and similar OS (HR, .59; 95% CI, .26-1.35; P = .21), with a median follow-up of 6.3 years in the TBI group and 6.6 years in the BEAM group. The 5-year PFS was 66% in the TBI group versus 52% in the BEAM group; OS was 82% versus 68%, respectively. However, on multivariate analysis, TBI-based conditioning was not significantly associated with PFS (HR, .57; 95% CI .24-1.34; P = .20), after controlling for age, disease status at ASCT, and receipt of post-transplantation rituximab maintenance. Likewise, early toxicity, nonrelapse mortality, and secondary malignancies were similar in the 2 groups. Our data suggest that both TBI and BEAM-based conditioning regimens remain viable conditioning options for patients with MCL undergoing ASCT.

Predicting life expectancy in patients with metastatic cancer receiving palliative radiotherapy: the TEACHH model.

BACKGROUND: Predicting life expectancy (LE) in patients with metastatic cancer who are receiving palliative therapies is a difficult task. The purpose of the current study was to develop a LE prediction model among patients receiving palliative radiotherapy (RT) that identifies those patients with short (< 3 months) and long (> 1 year) LEs. METHODS: The records of 862 patients with metastatic cancer receiving palliative RT at the Dana-Farber/Brigham and Women's Cancer Center between June 2008 and July 2011 were retrospectively reviewed. Cox proportional hazards models were used to evaluate established and potential clinical predictors of LE to construct a model predicting LE of < 3 months and > 1 year. RESULTS: The median survival was 5.6 months. On multivariate analysis, factors found to be significantly associated with a shorter LE were cancer type (lung and other vs breast and prostate), older age (> 60 years vs ≤ 60 years), liver metastases, Eastern Cooperative Oncology Group performance status (2-4 vs 0-1), hospitalizations within 3 months before palliative RT (0 vs ≥ 1), and prior palliative chemotherapy courses (≥ 2 vs 0-1). Patients were divided into 3 groups with distinct median survivals: group A (those with 0-1 risk factors), 19.9 months (95% confidence interval [95% CI, 13.9 months-31.1 months]); group B (those with 2-4 risk factors), 5.0 months (95% CI, 4.3 months -5.6 months); and group C (those with 5-6 risk factors), 1.7 months (95% CI, 1.2 months-2.1 months). CONCLUSIONS: The TEACHH model (type of cancer, Eastern Cooperative Oncology Group performance status, age, prior palliative chemotherapy, prior hospitalizations, and hepatic metastases) divides patients receiving palliative RT into 3 distinct LE groups at clinically informative extremes of the LE spectrum. It holds promise to assist radiation oncologists in tailoring palliative therapies to a patient's LE.

Impact of national guidelines on brachytherapy monotherapy practice patterns for prostate cancer.

BACKGROUND: In 1999 and 2000, 2 national guidelines recommended brachytherapy monotherapy (BT) primarily for treatment of low-risk prostate cancer but not high-risk prostate cancer. This study examined rates of BT use before and after publication of these guidelines, as compared with 4 other treatment options. METHODS: From 1990 to 2011, 8128 men with localized prostate cancer (≤ T3cN0M0) were treated definitively within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry with 1 of 5 primary treatments: BT, external beam radiotherapy (EBRT), EBRT with androgen deprivation therapy, EBRT+BT, or radical prostatectomy. Men were categorized into low-, intermediate-, and high-risk groups based on the guidelines' risk-group definitions. Within each risk group, logistic regression was used to estimate odds ratios (OR) comparing BT with other treatment options between the 1990-1998 and 1999-2011 periods, adjusting for age, disease characteristics, and clinic type. RESULTS: In total, 1117 men received BT alone for low- (n = 658), intermediate- (n = 244), or high-risk disease (n = 215). BT comprised 6.1% of all treatments in 1990-1998 versus 16.6% in 1999-2011 (P < .01). The odds of BT use remained increased after adjusting for potential confounders (OR = 3.06; P < .001) and was seen among low- (OR = 4.52; P < .001), intermediate- (OR = 2.67; P < .001), and even high-risk groups (OR = 2.11; P < .001). CONCLUSIONS: National guidelines did not appear to influence practice patterns, as BT monotherapy use increased relative to other treatments from the 1990-1998 to 1999-2011 periods in unfavorable risk groups including men with high-risk prostate cancer.

Key factors for establishing and sustaining a successful palliative radiation oncology program: a survey of the Society for Palliative Radiation Oncology.

BACKGROUND: Dedicated palliative radiation oncology programs (PROPs) within radiation oncology (RO) practices have been shown to improve quality and decrease costs of radiation therapy (RT) in advanced cancer patients. Despite this, relatively few PROPs currently exist, highlighting an unmet need to understand characteristics of the few existing PROPs and the potential barriers and facilitators that exist in starting and maintaining a successful PROP. We sought to assess the attributes of existing PROPs, the facilitators and barriers to establishing these programs, and the resources needed to create and maintain a successful program. METHODS: A 15-item online survey was sent to 157 members of the Society of Palliative Radiation Oncology (SPRO) in July 2019. RESULTS: Of the 157 members, 48 (31%) responded. Most practiced in an academic center (71% at main center and 15% at satellite) and 75% were from a larger group practice (≥6 physicians). Most (89%) believed the development and growth of a dedicated PROPs was either important (50%) or most important (39%) to the field of RO. Only 36% of respondents had a PROP, 38% wanted to establish one, and 13% were currently developing one. Of those with PROPs (N=16), 75% perceived an increase in the number of referrals for palliative RT since starting the program. A majority had an ability to refer to an outside palliative care specialist (64%), an outpatient RO service (53%), and specialized clinical processes for managing palliative radiotherapy patients (53%), with 41% having an inpatient RO consult service. Resources considered most essential were access to specialist-level palliative care, advanced practice provider support, a radiation oncologist with an interest in palliative care, having an outpatient palliative RO clinic, an emphasis on administering short radiation courses, and opportunities for educational development. Of those with a PROP or those who have tried to start one, the greatest perceived barriers to initiating a PROP were committed resources (83%), blocked out clinical time (61%), challenges coordinating management of patients (61%), and support from leaders/colleagues (61%). Perceived barriers to sustaining a PROP were similar. For those without a PROP, the perceived most important resources for starting one included access to palliative care specialist by referral (83%), published guidelines with best practices (80%), educational materials for referring physicians and patients (80%), educational sessions for clinical staff (83%), and standardized clinical pathways (80%). CONCLUSIONS: PROPs are not widespread, exist mainly within academic centers, are outpatient, have access to palliative care specialists by referral, and have specialized clinical processes for palliative radiation patients. Lack of committed resources was the single most important perceived barrier for initiating or maintaining a PROP. Best practice guidelines, educational resources, access to palliative care specialists and standardized pathways are most important for those who wish to develop a PROP. These insights can inform discussions and help align resources to develop, grow, and maintain a successful PROP.

Framework for Radiation Oncology Department-wide Evaluation and Implementation of Commercial Artificial Intelligence Autocontouring.

PURPOSE: Artificial intelligence (AI)-based autocontouring in radiation oncology has potential benefits such as standardization and time savings. However, commercial AI solutions require careful evaluation before clinical integration. We developed a multidimensional evaluation method to test pretrained AI-based automated contouring solutions across a network of clinics. METHODS AND MATERIALS: Curated data included 121 patient planning computed tomography (CT) scans with a total of 859 clinically approved contours used for treatment from 4 clinics. Regions of interest (ROIs) were generated with 3 commercial AI-based automated contouring software solutions (AI1, AI2, AI3) spanning the following disease sites: brain, head and neck (H&N), thorax, abdomen, and pelvis. Quantitative agreement between AI-generated and clinical contours was measured by Dice similarity coefficient (DSC) and Hausdorff distance (HD). Qualitative assessment was performed by multiple experts scoring blinded AI-contours using a Likert scale. Workflow and usability surveying was also conducted. RESULTS: AI1, AI2, and AI3 contours had high quantitative agreement in 27.8%, 32.8%, and 34.1% of cases (DSC >0.9), performing well in pelvis (median DSC = 0.86/0.88/0.91) and thorax (median DSC = 0.91/0.89/0.91). All 3 solutions had low quantitative agreement in 7.4%, 8.8%, and 6.1% of cases (DSC <0.5), performing worse in brain (median DSC = 0.65/0.78/0.75) and H&N (median DSC = 0.76/0.80/0.81). Qualitatively, AI1 and AI2 contours were acceptable (rated 1-2) with at most minor edits in 70.7% and 74.6% of ROIs (2906 ratings), higher for abdomen (AI1: 79.2%) and thorax (AI2: 90.2%), and lower for H&N (29.0/35.6%). An end-user survey showed strong user preference for full automation and mixed preferences for accuracy versus total number of structures generated. CONCLUSIONS: Our evaluation method provided a comprehensive analysis of both quantitative and qualitative measures of commercially available pretrained AI autocontouring algorithms. The evaluation framework served as a roadmap for clinical integration that aligned with user workflow preference.

Postoperative Radiation Therapy Is Indicated for "Low-Risk" Pathologic Stage I Merkel Cell Carcinoma of the Head and Neck Region but Not for Other Locations.

Purpose: The role of postoperative radiation therapy (PORT) in early stage Merkel cell carcinoma (MCC) is controversial. We analyzed the role of PORT in preventing local recurrences (LR) among patients with low-risk, pathologic stage I MCC based on the location of the primary tumors: head/neck (HN) versus non-HN sites. Methods and Materials: One hundred forty-seven patients with MCC were identified that had "low risk" disease (pathologic T1 primary tumor, negative microscopic margins, negative pathologic node status, no immunosuppression or prior systemic therapy). LR was defined as tumor recurrence within 2 cm of the primary surgical bed, and its frequency was estimated with the cumulative incidence method. Results: Seventy-nine patients received PORT (30 HN, 49 non-HN) with a median dose of 50 Gy (range, 8-64 Gy) and 68 patients were treated with surgery alone (30 HN, 38 non-HN). Overall, PORT was associated with a decreased risk of LR (5-year rate: 0% vs 9.5%; P = .004) with 6 LRs observed in the surgery alone group. Although the addition of PORT significantly reduced LR rates among patients with HN MCC (0% vs. 21%; P = .034), no LRs were observed in patients with non-HN MCC managed with surgery alone. There was no significant difference in MCC-specific survival comparing HN versus non-HN groups, with or without PORT. Conclusions: For low-risk, pathologic stage I MCC of the extremities and trunk, excellent local control rates were achieved with surgery, and PORT is not indicated. However, PORT was associated with a significant reduction in LRs among low-risk MCC of the HN.

External Beam Radiation Therapy for Palliation of Symptomatic Bone Metastases: An ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides evidence-based recommendations for palliative external beam radiation therapy (RT) in symptomatic bone metastases. METHODS: The ASTRO convened a task force to address 5 key questions regarding palliative RT in symptomatic bone metastases. Based on a systematic review by the Agency for Health Research and Quality, recommendations using predefined consensus-building methodology were established; evidence quality and recommendation strength were also assessed. RESULTS: For palliative RT for symptomatic bone metastases, RT is recommended for managing pain from bone metastases and spine metastases with or without spinal cord or cauda equina compression. Regarding other modalities with RT, for patients with spine metastases causing spinal cord or cauda equina compression, surgery and postoperative RT are conditionally recommended over RT alone. Furthermore, dexamethasone is recommended for spine metastases with spinal cord or cauda equina compression. Patients with nonspine bone metastases requiring surgery are recommended postoperative RT. Symptomatic bone metastases treated with conventional RT are recommended 800 cGy in 1 fraction (800 cGy/1 fx), 2000 cGy/5 fx, 2400 cGy/6 fx, or 3000 cGy/10 fx. Spinal cord or cauda equina compression in patients who are ineligible for surgery and receiving conventional RT are recommended 800 cGy/1 fx, 1600 cGy/2 fx, 2000 cGy/5 fx, or 3000 cGy/10 fx. Symptomatic bone metastases in selected patients with good performance status without surgery or neurologic symptoms/signs are conditionally recommended stereotactic body RT over conventional palliative RT. Spine bone metastases reirradiated with conventional RT are recommended 800 cGy/1 fx, 2000 cGy/5 fx, 2400 cGy/6 fx, or 2000 cGy/8 fx; nonspine bone metastases reirradiated with conventional RT are recommended 800 cGy/1 fx, 2000 cGy/5 fx, or 2400 cGy/6 fx. Determination of an optimal RT approach/regimen requires whole person assessment, including prognosis, previous RT dose if applicable, risks to normal tissues, quality of life, cost implications, and patient goals and values. Relatedly, for patient-centered optimization of treatment-related toxicities and quality of life, shared decision making is recommended. CONCLUSIONS: Based on published data, the ASTRO task force's recommendations inform best clinical practices on palliative RT for symptomatic bone metastases.

Radiation Therapy for Painful Bone Metastases: Fractionation, Recalcification, and Symptom Control.

Bone is a common site for metastases, which may cause pain and other skeletal-related events (SRE) in patients with advanced cancer. Since the 1980s, prospective clinical trials have demonstrated the high efficacy of external beam radiotherapy (EBRT) for pain relief from focal, symptomatic lesions. In uncomplicated bone metastases, which include those without pathologic fracture, evidence of cord compression, or prior surgical intervention, improvement or complete pain relief with radiotherapy is as high as 60%, with no difference in efficacy when radiotherapy is delivered in a single or multiple fractions. The ability to treat with a single fraction makes EBRT an attractive therapy even for patients with poor performance status and/or life expectancy. Even in patients with complicated bone metastases (eg cord compression), several randomized trials have demonstrated similar rates of pain relief in addition to improved functional outcomes such as ambulation. In this review, we summarize the role of EBRT for alleviating painful bone metastases and explore its role for other endpoints including functional outcomes, recalcification, and prevention of SREs.

Matching Protocol and Practice: The Challenge of Meeting Lung and Kidney Total Body Irradiation Constraints for Scleroderma.

PURPOSE: Total body irradiation (TBI), a form of immunomodulation, improves treatment outcomes for rapidly progressive scleroderma. The landmark Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial used strict 200-cGy lung and kidney dose restrictions to limit the likelihood of normal tissue toxicity. The protocol as written did not specify how or where the 200-cGy limit was to be measured, opening the door to variable techniques and outcomes. METHODS AND MATERIALS: Following the SCOT protocol, a validated 18-MV TBI beam model was used to evaluate lung and kidney doses with varying Cerrobend half-value layers (HVLs). Block margins were constructed per the SCOT protocol. RESULTS: Using the 2 HVL SCOT block guidelines, the average central point dose under the lung block center was 353 (±27) cGy, almost double the mandated 200 cGy. The mean lung dose was 629 (±30) cGy, triple the mandated 200 cGy. No block thickness could achieve the mandated 2 Gy due to contribution from unblocked peripheral lung tissue. With 2 HVLs, the average kidney dose was 267 (±7) cGy. Three HVLs were needed to reduce it <200 cGy, meeting the mandated SCOT limit. CONCLUSIONS: There is considerable ambiguity (and inaccuracy) in lung and kidney dose modulation for TBI. It is not possible to achieve the mandated lung doses using the protocol-specified block parameters. Future investigators are encouraged to take these findings into account to develop more explicit, achievable, reproducible, and accurate TBI methodology.

Emergent radiotherapy for brain and leptomeningeal metastases: a narrative review.

BACKGROUND AND OBJECTIVE: As novel systemic therapies allow patients to live longer with cancer, the risk of developing central nervous system (CNS) metastases increases and providers will more frequently encounter emergent presentation of brain metastases (BM) and leptomeningeal metastases (LM). Management of these metastases requires appropriate work-up and well-coordinated multidisciplinary care. We set out to perform a review of emergent radiotherapy (RT) for CNS metastases, specifically focusing on BM and LM. METHODS: We review the appropriate pathways for workup and initial management of BM and LM, while reviewing the literature supporting emergent treatment of these entities with surgery, systemic anti-cancer therapy, and RT. To inform this narrative review, literature searches in PubMed and Google Scholar were conducted, with preference given to articles employing modern RT techniques, when applicable. Due to the paucity of high-quality evidence for management of BM and LM in the emergent setting, discussion was supplemented by the authors' expert commentary. KEY CONTENT AND FINDINGS: This work highlights the importance of surgical evaluation, particularly for patients presenting with significant mass effect, hemorrhagic metastases, or increased intracranial pressure. We review the rare situations where emergent initiation of systemic anti-cancer therapy is indicated. When defining the role of RT, we review factors guiding selection of appropriate modality, treatment volume, and dose-fractionation. Generally, 2D- or 3D-conformal treatment techniques prescribed as 30 Gy in 10 fractions or 20 Gy in 5 fractions, should be employed in the emergent setting. CONCLUSIONS: Patients with BM and LM present from a diverse array of clinical situations, requiring well-coordinated multidisciplinary management, and there is a paucity of high-quality evidence guiding such management decisions. This narrative review aims to more thoroughly prepare providers for the challenging situation of emergent management of BM and LM.

Emergent radiotherapy for spinal cord compression/impingement-a narrative review.

BACKGROUND AND OBJECTIVE: Malignant epidural spinal cord compression (MESCC), often presenting with back pain and motor/sensory deficits, is associated with poor survival, particularly when there is loss of ambulation. The purpose of this review is to evaluate the literature and discuss appropriate workup and management of MESCC, specifically in the emergent setting. METHODS: A PubMed search was conducted on "spinal cord compression" and "radiation therapy." Articles were analyzed for the purpose of this narrative review. KEY CONTENT AND FINDINGS: If MESCC is suspected, neurologic examination and complete spine imaging are recommended. Emergent treatment is indicated if there is radiographic evidence of high-grade compression and/or clinically significant motor deficits. Treatment involves a combination of medical management, surgical decompression, radiation therapy (RT), and rehabilitation. For motor deficits, emergent initiation of high dose steroids is recommended. Circumferential surgical decompression ± stabilization followed by RT provides superior clinical outcomes than RT alone. For patients whom surgery is not reasonable, RT alone may provide significant treatment response which depends on radioresponsiveness of the pathology. Systemic therapy, if indicated, is typically reserved till after primary treatment of MESCC, but patients with chemoresponsive tumors may receive primary chemotherapy. The selected RT schedule should be personalized to each patient and commonly is 30 Gy in 10 fractions (fx), 20 Gy in 5 fx, or 8 Gy in 1 fx. MESCC recurrence may be treated with additional RT, if within the spinal cord tolerance, or surgery. Stereotactic body radiation therapy (SBRT) has been used for high grade MESCC in patients with relatively intact neurologic function at a few centers with a very robust infrastructure to support rapid initiation of treatment within a short period of time, but is generally not feasible for most clinical practices. SBRT may be advantageous for low grade MESCC, recurrence, or in the post-operative setting. Detection of MESCC prior to development of high-grade compression or deterioration of neurologic function may allow patients to benefit more from advanced therapies and improve prognosis. CONCLUSIONS: MESCC is a devastating condition; optimal treatment should be personalized to each patient and approached collaboratively by a multidisciplinary team.

Posttreatment prostate specific antigen nadir predicts prostate cancer specific and all cause mortality.

PURPOSE: We investigated whether the prostate specific antigen nadir predicts prostate cancer specific and all cause mortality in men treated in a randomized trial of radiation with or without 6 months of androgen deprivation therapy. MATERIALS AND METHODS: The study included 204 men with cT1b-T2bN0M0 prostate adenocarcinoma and at least 1 unfavorable factor, including prostate specific antigen less than 10 to 40 ng/ml, Gleason 7 or greater, or T3 on magnetic resonance imaging. We performed Fine and Gray regression, and Cox multivariable analysis to determine whether an increasing prostate specific antigen nadir was associated with prostate cancer specific and all cause mortality, adjusting for treatment, age, Adult Comorbidity Evaluation 27 score and cancer prognostic factors. RESULTS: At a 6.9-year median followup median prostate specific antigen nadir was 0.7 ng/ml for radiation alone and 0.1 ng/ml for radiation plus androgen deprivation therapy. The prostate specific antigen nadir (adjusted HR 1.18/ng/ml increase, 95% CI 1.07-1.31, p=0.001) and Gleason 8 or greater (adjusted HR 8.05, 95% CI 1.01-64.05, p=0.049) significantly predicted increased prostate cancer specific mortality. Moderate/severe comorbidity carried a decreased risk (adjusted HR 0.13, 95% CI 0.02-0.96, p=0.045). Higher prostate specific antigen nadir (adjusted HR 1.10/ng/ml increase, 95% CI 1.04-1.17), older age (adjusted HR 1.10/year, 95% CI 1.04-1.15) and interaction between comorbidity score and randomization arm (each p<0.001) increased the all cause mortality risk. Men who achieved a prostate specific antigen nadir of the median value or less had lower estimated prostate cancer specific and all cause mortality at 7 years (3.7% vs 18.3%, p=0.0005 and 31.5% vs 55.0%, p=0.002). CONCLUSIONS: Posttreatment prostate specific antigen nadir is significantly associated with the risk of prostate cancer specific and all cause mortality after radiation with or without androgen deprivation therapy. A suboptimal prostate specific antigen nadir may identify candidates for earlier intervention to prolong survival.