Initial Radiotherapy Research Articles

Medical Conditions Among Survivors of Adolescent and Young Adult Non-Hodgkin Lymphoma (NHL), Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML)

Introduction: Adolescent and young adult (AYA) cancer survivors are at an increased risk of developing subsequent medical problems, including asthma/chronic obstructive pulmonary disorder, cardiovascular disease, diabetes and second cancers. However, few population-based studies have focused on these risks in AYAs with NHL, ALL or AML or considered whether the occurrence of these and other medical conditions differ by sociodemographic factors.Methods: Data for patients aged 15-39 when diagnosed with NHL (n=4,459), ALL (n=1,100) and AML (n=1,107) during 1996-2012 and surviving a minimum of 2 years were obtained from the California Cancer Registry and followed in California hospital discharge databases. Discharge diagnoses were used to classify medical conditions as cardiac (hypertensive disease, ischemic heart disease, other heart disease), neurologic (stroke, seizure), endocrine (hypothyroidism, diabetes, ovarian/testicular dysfunction, other metabolic diseases), respiratory (asthma, chronic obstructive pulmonary disease), renal (chronic kidney disease, hemodialysis, kidney transplant), liver (chronic liver disease, pancreatitis, cirrhosis, liver transplant), and avascular necrosis. Second cancers were obtained from the cancer registry. We estimated the cumulative incidence (CMI) of developing each condition 10-years after diagnosis, accounting for death as a competing risk. We determined the impact of race/ethnicity, neighborhood socioeconomic status (SES), health insurance status and stem cell transplant (SCT) on the occurrence of each medical condition after adjusting for other demographic and clinical factors using multivariable Cox proportional hazards regression.Results: The most common medical conditions among AYA survivors at 10-years were cardiac (CMI NHL: 11.6%; ALL= 20.5%; AML= 18.2%), endocrine (CMI NHL: 18.6%; ALL= 33.0%; AML= 25.9%) and respiratory (CMI NHL: 5.1%; ALL= 7.7%; AML= 6.8%) diseases. Avascular necrosis had the highest CMI in ALL patients (CMI NHL: 1.2%; ALL= 8.7%; AML= 2.5%). Neurologic (CMI NHL: 2.1%; ALL= 4.5%; AML= 4.9%) and liver (CMI NHL: 2.0%; ALL= 5.6%; AML= 4.4%) were more common in survivors of ALL and AML than NHL. Second cancers (2.3-2.5%) and renal diseases (2.2-3.5%) were less common at 10-years. NHL survivors with advanced stage disease had a higher incidence of all medical conditions, except second cancers. Chemotherapy was associated with a higher CMI of cardiac and endocrine conditions among NHL survivors; these associations could not be assessed in ALL and AML patients as nearly all patients received chemotherapy. Initial radiation therapy was not associated with a higher CMI of medical conditions in NHL or ALL survivors, but was associated with a higher CMI of respiratory, renal and endocrine diseases in AML survivors. In multivariable models, public or no insurance (vs private) was associated with a higher risk of most medical conditions in NHL and ALL survivors, but not AML survivors (Table). The risk of developing medical conditions varied by race/ethnicity, with Hispanics ALL survivors (vs non-Hispanic whites) at a higher risk of cardiac, renal, liver, endocrine, second cancers and neurologic diseases and black AML survivors at a higher risk of all medical conditions, except endocrine diseases. AYAs with NHL who resided in lower SES neighborhoods were at a higher risk for developing cardiac, respiratory and endocrine diseases; AML survivors in lower SES neighborhoods had a higher risk of respiratory diseases. Across all cancers, AYAs undergoing a SCT were at a higher risk of most medical conditions.Conclusion: This study found that sociodemographic factors were associated with the risk of developing medical conditions in AYA NHL, ALL and AML survivors. As expected, the risk of medical conditions varied by cancer type and treatment, with those undergoing SCT having a higher risk of medical conditions regardless of cancer type. NHL and ALL survivors who were uninsured or publicly insured were at a consistently higher risk of developing medical conditions, as were Hispanic ALL survivors and Black AML survivors. Our findings highlight the higher burden of medical conditions in subgroups of cancer survivors that may relate to reduced access to preventive care, early detection/intervention and long-term surveillance. DisclosuresMuffly:Shire Pharmaceuticals: Research Funding; Adaptive Biotechnologies: Research Funding.

Access to Initial Treatment Was Not the Driving Force of the Survival Disparity By Insurance Status in Follicular Lymphoma — an Analysis of the National Cancer Database (NCDB)

Background:Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. The initial management varies from watchful waiting to a combination of chemoimmunotherapy (CT) and radiation therapy (RT). Goldstein et al. recently reported (Blood, pre-published online, July 24 2018) that FL patients with no insurance or Medicaid had worse OS. We examined whether the survival discrepancy was caused by access to initial treatment using the National Cancer Database (NCDB).Methods:FL cases diagnosed from year 2004-2015 in NCDB were included. Demographic characteristics were compared using Chi-square test for categorical variables and ANOVA for continuous variables. Use of CT and RT was analyzed in multivariate logistic regression including the following variables: age, gender, race, Hispanic ethnicity, stage, grade, primary site extranodal, facility type, urban/rural location, distance to facility, year period of diagnosis (2004-2010 vs 2011-2015), education, income and insurance status. Overall survival (OS) was analyzed using Cox proportional hazard model including the same covariates with addition of CT and RT.After Jan 2013, rituximab was captured as immunotherapy. To assess the use of rituximab, we compared immunotherapy in years 2014 and 2015 to avoid possible data entry error in 2013.The treatment modalities and OS were similar for uninsured and Medicaid patients, and for Private and Medicare patients after adjusting for covariates. We combined “uninsured” and “Medicaid” into “Less” insurance and “Private” and “Medicare” into “Increased” insurance.Results:A total of 94057 FL cases were included in the analysis with the following insurance status: Uninsured 2723 (2.9%), Medicaid 3804 (4.0%), Private insurance 43354 (46.1%), and Medicare 44176 (47.0%).Patients with no insurance or Medicaid were more likely to present at an advanced stage (Table 1).In the multivariate model, less insurance was associated with less initial use of radiation therapy (OR=0.87, p=0.003) and more use of CT (OR=1.28 p<0.0001). For patients diagnosed in years 2014 and 2015, initial use of immunotherapy (most likely rituximab) and the waiting time before starting immunotherapy did not differ by insurance status.Both less insurance and not-receiving radiation therapy were associated with worse OS after adjusting for covariates (HR=1.96 and 1.30, respectively, p<0.0001 for both, Table 3, Figure 1). Chemoimmunotherapy was not associated with OS. Lower education and income were both associated with worse OS after adjusting for insurance (Table 3).RT is recommended as frontline treatment for suitable patients with early stage (stage I/II) low grade (grade 1/2) FL. We analyzed the use of RT and survival outcome in this patient group. The results were similar to results for the entire patient set. Patients with less insurance received RT less often (21.7% vs 24.7%, p=0.02), and when they did receive radiation therapy, the waiting time before starting treatment was longer (89 days vs 79 days, respectively, p=0.02). Both less insurance and not-receiving RT were associated with worse OS (p<0.0001 for both, Table 4).Conclusion:Follicular lymphoma patients with no insurance or Medicaid had worse OS. Less insurance was associated with decreased access to initial radiation therapy but not chemoimmunotherapy. However the survival discrepancy cannot be solely explained by access to radiation therapy given the magnitude of difference. Moreover, insurance remains a significant predictor of survival after adjusting for initial treatment. The key drivers of the survival discrepancy by insurance status in FL patients need to be further defined. [Display omitted] DisclosuresFeldman:Portola: Research Funding; KITE: Speakers Bureau; Celgene: Speakers Bureau; Pharmacyclics: Speakers Bureau; Janssen: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau; Johnson and Johnson: Speakers Bureau. Chang:Incyte: Research Funding.

Long-term survival and late complications of intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma

BackgroundTo evaluate the effectiveness and toxicities of intensity-modulated radiotherapy (IMRT) for locally recurrent nasopharyngeal carcinoma (NPC).MethodsOne hundred and eighty-four previously irradiated NPC patients with recurrent disease and re-irradiated by IMRT between February 2005 to May 2013 had been reviewed. The disease was re-staged I in 33, II in 27, III in 70 and IV in 54 patients. Seventy-five percent of the patients received cisplatin-based chemotherapy.ResultsThe median survival time was 33 months. The 3-year actuarial rates of local recurrence–free survival (LRFS), distant metastases–free survival (DMFS), and overall survival (OS) rates were 85.1, 91.1, and 46.0%, respectively. About 53% of the patients experienced Grade 3–4 late toxicities. Forty-four patients died of massive hemorrhage of the nasopharynx caused by radiation induced mucosal necrosis. Multivariate analysis indicated that chemotherapy and time interval between initial radiotherapy and re-irradiation were independent predictors for DMFS.ConclusionIMRT is an effective method for patients with locally recurrent NPC. Massive hemorrhage of the nasopharynx is the major sever late complication and also the leading cause of death. Early recurrence is negative factor for DMFS. Combination of chemotherapy can improve DMFS, but not for OS. Optimal salvage treatment strategies focusing on improvement of survival and minimization of late toxicities are warranted.

Salvage surgery for a locally persistent or recurrent tumour in maxillary cancer patients who have undergone radiotherapy and concomitant intra-arterial cisplatin: implications for surgical margin assessment

Limited information about salvage surgery is available for locally persistent and recurrent maxillary sinus cancers after the completion of chemoradiation therapy. Seventy-six maxillary sinus cancer patients who had undergone chemoradioselection using initial radiotherapy and concomitant intra-arterial cisplatin were screened retrospectively. Twenty-four of these patients who had a locally persistent or recurrent tumour were investigated. The 2-year overall survival rate of patients with maxillary sinus cancer of all types was 39.0% for those who underwent salvage surgery and 10.0% for those who did not. The 2-year overall survival rate of patients with maxillary sinus squamous cell carcinoma was 45.8% for those who underwent salvage surgery and 11.1% for those who did not. Furthermore, the 2-year local control and overall survival rates of patients with positive and negative surgical margins were 14.3% and 83.3% and 14.3% and 66.7%, respectively. There were significant differences in local control (P=0.004) and overall survival (P=0.005) regarding surgical margin status. Although salvage surgery for a locally persistent or recurrent maxillary sinus cancer is a feasible treatment, patients with positive surgical margins are more prone to local relapse. Therefore, surgical safety margins should be assessed thoroughly.

Substantial Volume Changes and Plan Adaptations During Preoperative Radiation Therapy in Extremity Soft Tissue Sarcoma Patients

PurposeMany authors suggest that extremity soft tissue sarcomas (ESTS) do not change significantly in size during preoperative radiation therapy (RT). This cone beam computed tomography study investigates the justification to deliver the entire course with 1 initial RT plan by observing anatomic changes during RT. Methods and MaterialsBetween 2015 and 2017, 99 patients with ESTS were treated with either curative (n = 80) or palliative intent (n = 19) with a regimen of at least 6 fractions. The clinical target volume to planning target volume margin was 1 cm. Action levels were assigned by radiation technicians. An extremity contour change of >1 cm and/or tumor size change >0.5 cm required a physician's action before the next fraction. ResultsA total of 982 cone beam computed tomography logfiles were studied. In 41 of 99 patients, the dose coverage of the initial treatment plan was fully satisfactory throughout the RT course. However, action levels were observed in 58 patients (59%). In 41 of these 58 patients, a contour increase of 5 to 23 mm was noted (29 tumor size increase only, 3 extremity contour increase, and 9 both). In 21 of 58 patients, a decrease of 5 to 33 mm was observed (20 tumor size decrease only and 1 tumor size decrease and extremity contour decrease). In 4 cases, contours initially increased and subsequently decreased. In 33 of 41 patients with increasing contours, the dose distribution adequately covered gross tumor volume because of the 1 cm planning target volume margin applied. For the remaining 8 patients (8%), the plan needed to be adapted. ConclusionsESTS volumes may change substantially during RT in 59% of all patients, leading to plan adaptations resulting from increased volumes in 8%. Daily critical observation of these patients is mandatory to avoid geographic misses because of increases in size and overdosing of normal tissues when masses shrink.

Re-irradiation for Paediatric Tumours

Despite best available therapy, many children with cancer develop recurrence after multimodal treatment, including initial radiation therapy. Re-irradiation is defined as the use of a second course of radiation therapy with a retreatment volume that overlaps substantially with that of a previously delivered course of radiation therapy. Re-irradiation is an important part of salvage treatment for patients with recurrent ependymoma, diffuse intrinsic pontine glioma, medulloblastoma and germinoma. In patients with ependymoma, conventionally fractionated re-irradiation (1.8 Gy/day) can provide long-term disease control with low rates of high-grade toxicity. For children with progressive diffuse intrinsic pontine glioma, re-irradiation provides effective palliation of symptoms and a survival gain as compared with those treated without re-irradiation. Repeat radiation therapy that includes craniospinal irradiation, if safe to deliver, may provide long-term tumour control in patients with medulloblastoma. Patients with recurrent intracranial germinoma can be effectively salvaged with re-irradiation that includes craniospinal irradiation. Finally, the emerging role of re-irradiation in non-brainstem high-grade glioma and extracranial solid tumours requires further study regarding its efficacy and safety. When given, re-irradiation should be delivered with care so that doses to organs at risk are minimised. In all cases, re-irradiation should be considered as an option alongside, or concurrently with, other salvage treatments, including surgery or systemic therapy, to maximise the likelihood of durable disease control.

Pediatric Central Nervous System Atypical Teratoid/Rhabdoid Tumor: Early and Aggressive Post-Operative Radiation Therapy Provides Better Outcome

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and highly aggressive pediatric CNS malignant tumor mainly affects infants and young children. The purpose of the study is to evaluate the possible prognostic factors and optimal management for this rare disease. Twenty-eight pediatric patients of CNS AT/RT treated with radiation therapy (RT) as part of multimodality treatment at one institution between 1996 and 2015 were retrospectively reviewed. Progression free survival (PFS), overall survival (OS), and neuro-axis failure free survival were analyzed in correlation with possible prognostic factors. The median age at diagnosis was 4.3 years old (range 0.6-19 years), with 12 patients (42.9%) less than 3 years old. Six patients (21.4%) had neuro-axis spreading at diagnosis. Radiotherapy was delayed for a longer period after surgery in patients less than 3 years old compared to older ones, with mean interval 4.9 and 1.9 months, respectively (p=0.06). Chemotherapy was given before RT initiation in 14 patients (50.0%). All of the patients ≥ 3 years old received cranio-spinal irradiation (CSI) followed by boost to tumor bed, while only 4 patients < 3 years-old(33.3%) did so (p<0.01). Mean dose to the primary tumor bed was 48.7 Gy (range 30.0-56.0 Gy), and mean CSI dose was 29.8Gy (range 24.0-36.0 Gy). Seven of 12 patients < 3 years old received high dose chemotherapy and autologous peripheral blood stem cell (PBSC) rescue. The median follow-up period was 45 months. The median PFS was 11 months and OS was 67 months. Three-year PFS was 46.4%, and OS was 60.7%. At the end of follow-up, 15 patients (53.6%) suffered from disease relapse; 13 of them had disseminating neuraxis seeding, and 11 died within one year after relapse. Interval between surgery and RT > 2 months (HR= 3.38, p=0.01) was correlated with worse PFS, while higher tumor bed RT dose (HR 0.9, p<0.01) was associated with better PFS. Overall survival was significantly worse with interval between surgery and RT > 2 months (HR=3.54, p=0.02). Cranio-spinal irradiation increased neuraxis failure free survival (HR 0.36, p= 0.05). In the group of patients < 3 years old, high dose chemotherapy followed by autologous PBSC rescue was associated with better OS compared to intravenous +/- intra-thecal chemotherapy alone (HR 0.15, p=0.04). Early and aggressive RT immediately after surgery is critical for disease control. Prognosis is extremely poor after relapse. For younger patients, high dose chemotherapy with autologous PBSC rescue provides better outcome, and may be considered as an alternative treatment to cranio-spinal irradiation.

Long-Term Survival and Late Complications of Intensity-Modulated Radiation Therapy for Recurrent Nasopharyngeal Carcinoma

To evaluate the effectiveness and toxicities of intensity-modulated radiotherapy (IMRT) for locally recurrent nasopharyngeal carcinoma (NPC). One hundred eighty-four previously irradiated NPC patients with recurrent disease and re-irradiated by IMRT between February 2005 to May 2013 had been reviewed. The disease was re-staged I in 33, II in 27, III in 70 and IV in 54 patients. Seventy-five percent of the patients received cisplatin-based chemotherapy. The median survival time was 33 months. The 5-year actuarial rates of local recurrence–free survival (LRFS), distant metastases–free survival (DMFS), and overall survival (OS) rates were 71.7%, 85.9%, and 28.8%, respectively. About 53% of the patients experienced Grade 3-4 late toxicities. Forty-four patients died of massive hemorrhage of the nasopharynx caused by radiation induced mucosal necrosis. Multivariate analysis indicated that chemotherapy and time interval between initial radiotherapy and re-irradiation were independent predictors for DMFS. IMRT is an effective method for patients with locally recurrent NPC. Massive hemorrhage of the nasopharynx is the major sever late complication and also the leading cause of death. Early recurrence is negative factor for DMFS. Combination of chemotherapy can improve DMFS, but not for OS. Optimal salvage treatment strategies focusing on improvement of survival and minimization of late toxicities are warranted.

Effect of Radiation Boost Modality in Overall Survival of Cervical Cancer Patients

To evaluate the efficacy of radiation boost modality in locally advanced cervical cancer patients treated with initial external beam radiation therapy (EBRT) and chemotherapy. We have analyzed National Cancer Database for FIGO stage IB-IIIB cervical cancer patients treated from 2004 to 2014. Considered non-surgical patients who received both chemotherapy and EBRT. Included patients (n = 9,936) received primary/initial treatment with either intensity modulated radiation (IMRT) or 3D conformal radiotherapy (3D-CRT) of 40-60Gy dose. We have considered three options for radiation boost: no boost, EBRT boost and brachytherapy (BT) boost. Patients who had EBRT boost dose 10-40Gy were included in this study. Statistical software was used for statistical analysis; p-value < 0.05 was considered statistically significant. The median age of the patients was 51 years (range: 18-90yrs). The median follow-up was 33.8 months (range: 6.2-143.1mo). Mean/median overall survival (OS) in months were: 69.7/52.1, 63.5/38.2 and 90.8/112.9 for no boost, EBRT boost and BT boost, respectively. Observed marginal differences in OS between patients treated with no boost and EBRT boost modalities. However, the OS of the patients treated with BT boost modality was much higher as compared to that of other two groups, i.e. no boost and EBRT boost. The same trend was observed across the clinical stages IB-IIIB (Table 1). All these differences in OS were statistically significant (p<0.05). This study indicates that the BT boost is superior to EBRT boost modality for overall survival in locally advanced cervical cancer patients. Therefore, every effort should be made to use BT boost in treating cervical cancer patients with curative intent.Abstract TU_13_3443: Table 1Overall survival (OS; mean/ median in months) of stage IB-IIIB cervical cancer patients.Initial/Primary Tx modalityEBRT (40-60Gy) + Chemotherapyp-valueBoost Tx modalityNo boostEBRT boostBT boostNo. of patients2,003 (20.2%)902 (9.1%)7,031 (70.7%)OS for all patients69.7/ 52.163.5/ 38.290.8/ 112.9<0.001OS for Stage IB pts.91.1/ 120.372.2/ 71.9102.1/ 133.6<0.001OS for Stage II pts.83.5/ 105.573.8/ 65.696.3/ 127.9<0.001OS for Stage III pts.52.1/ 24.657.8/ 29.179.3/ 71.6<0.001 Open table in a new tab

Nasal Colonization with Staphylococcus Aureus Before Radiation Therapy Predicts Radiation Dermatitis: A Prospective Study

Acute radiation dermatitis (RD) is a common side effect of radiation therapy (RT). Radiation-induced skin changes are thought to increase the risk of secondary skin infection. However, little is known regarding the baseline incidence of microbial colonization prior to RT and whether it is associated with development of RD. The goals of our prospective study are to 1) characterize the incidence of baseline bacterial colonization in patients undergoing RT, and 2) examine the association between radiation dermatitis severity and baseline bacterial colonization. We hypothesize that microbial colonization prior to initiation of RT is associated with development of RD. We are presenting preliminary results from a prospective trial in which patients with cancers of the head and neck, breast, or anus undergo bacterial culture from the nares and the area of skin subject to radiation, prior to RT initiation. Patients are evaluated weekly during RT, and dermatitis is graded using CTCAE version 4.0. Descriptive statistics and odds ratios are utilized to present associations between culture results and skin toxicity. Forty-eight subjects with cancers of the breast (48%), head and neck (44%), and anus (8%) have completed RT to date. Baseline bacterial culture for Staphylococcus aureus was positive in the nares for 10 subjects (21%) and positive on the skin in 3 subjects (6%). All 3 subjects with positive skin cultures also had a positive nares culture. Twenty-eight patients (58%) developed grade 1 dermatitis, 15 (31%) developed grade 2 dermatitis, and 5 (10%) developed grade 3 dermatitis. 18 subjects (38%) received silver sulfadiazine for RD. Positive culture for S. aureus at baseline was associated with increased risk of grade 2-3 dermatitis (80% v. 32%, OR=8.7, p=0.012) and with receipt of silver sulfadiazine (70% v. 29%, OR=5.7, p=0.025). Bacterial colonization with S. aureus prior to RT initiation is a risk factor for developing high-grade RD. Because a positive nares culture was able to predict skin toxicity, even in the absence of a positive skin culture, antimicrobial therapy in the nares prior to RT initiation ought to be explored as a strategy to lessen the severity of RD. Further studies are needed to understand the association between microbial colonization and development of RD.

Secondary Breast Cancer after DCIS: Impact of Initial Radiation Therapy on Mortality Associated with Invasive Second Breast Cancers

Secondary Breast Cancer after DCIS: Impact of Initial Radiation Therapy on Mortality Associated with Invasive Second Breast Cancers

Nano-Based Quantification of Circulating Tumor Cells as a Biomarker of Disease Status in Oligometastatic Patients Following Metastases-Directed Radiation Therapy

Circulating tumor cells (CTCs) have been demonstrated as a biomarker in certain advanced cancers. Additionally, there has been increasing recognition that definitive treatment, including radiotherapy (RT), may lead to cure or significantly increased time to progression in oligometastatic solid malignancies. However, differentiating between patients with truly oligometastatic disease and those who will develop systemic disease is difficult. In most cases, secondary to a lack of reliable biomarker, surveillance often relies heavily on imaging. We hypothesized that CTCs are a sensitive biomarker in post-treatment surveillance after metastasis-directed definitive RT in oligometastatic patients. Patients with oligometastatic solid-tumor malignancies with up to 3 metastases undergoing definitive RT to all known metastatic sites were enrolled on a prospective study. Peripheral blood (7 mL) was drawn prior to initiation of RT, 1-3 time points during RT, and at subsequent follow up appointments. CTCs were quantified using CapioCyte, a nanotechnology based CTC capture system that takes advantage of biomimetic cell rolling and dendrimer-mediated strong multivalent binding. A total of 33 patients were enrolled with a median follow-up of 12.4 months. All patients had detectable CTCs on enrollment with a median of 24 CTCs/mL (range 3-120). Pre-treatment CTCs did not predict subsequent recurrence (p=0.94). 20 patients (67%) subsequently had progression of disease, with an overall median PFS of 4.6 months. Of those who recurred, 10 patients had CTCs quantified at or near the time of progression, with 8 of these patients showing a corresponding increase in CTCs (2.5-28.7 fold increase). Out of 6 patients who were started on systemic therapy after progression, CTCs declined or were stable in all 5 patients with a partial response or stable disease, and increased in 1 patient who progressed. Our data suggests CTCs as quantified by the CapioCyte technology correspond with disease status and are a reliable biomarker for post-treatment surveillance in oligometastatic solid-tumor malignancies.

Concurrent Radiation and Immunotherapy: Survey of Practice Patterns in the United States

Rapid FDA approval of multiple immunotherapy (IT) drugs for a variety of advanced and metastatic cancers, coupled with a current void of published clinical data on toxicity and outcomes from concurrent radiation (RT) and immunotherapy (IT) (CRI), leave radiation oncologists (ROs) with uncertainty regarding their concurrent administration. A survey to determine current practice patterns, experiences, and perceptions of CRI may help guide ROs until more definitive data is available. A survey was emailed to ROs over a 1-week period in February 2018. Responses were collected on Survey Monkey and descriptive statistics were used to report results. CRI was defined as RT completed within 1 week prior to initial IT infusion through 4 weeks after the final IT infusion. Of the 304 respondents from 44 states, 87.5% had experience treating a patient with CRI, including 50% private and 48% academic physicians. Results from the 266 ROs with prior CRI experience are summarized below. The majority of respondents have had limited experience with CRI: 60%, 56%, and 50% of respondents treated 1-5 patients on nivolumab, pembrolizumab, or ipilimumab, respectively, while 11-21%, 6-11%, and 4-8% have treated 5-10, 10-20 and >20 patients, respectively. 59% used CRI off-study, including 20% who prescribed a definitive RT course with concurrent IT. RT dose mostly was not altered: 13-15% decreased RT dose if treating the C/A/P, while 4-9% decreased dose in the brain, H/N, or extremities. For palliative RT vs SBRT/SRS to non-extremity sites, 65-67% vs 57-60% would not delay initiation of RT from IT infusion, while 12% vs 17-19% would wait ≥2 weeks from last IT infusion. For palliative RT vs SBRT to extremities, 80% vs 70% would not delay RT, but 5 vs 14% would wait 2 weeks. The two most common reasons for not offering CRI were due to concerns of increased toxicity (51%) or waiting to see response from newly initiated IT (40%). Moderate and significant toxicities were rare for all treatment sites and RT doses (medical intervention 6%, hospitalization/death <1%). 98% of ROs have not routinely prescribed prophylactic steroids for CRI. 49-59% of respondents remained uncertain if CRI vs RT monotherapy was improving local control or increasing abscopal responses, yet more ROs believed CRI with SBRT/SRS vs palliative RT had better local control (35% vs 25%) and higher rates of abscopal responses (40% vs 26%). Amongst the 38 ROs without prior CRI experience, 60% were concerned about increased toxicity, 32% would wait >2 weeks from IT to start SBRT/SRS, and 25% would offer prophylactic steroids. Despite concerns for toxicity, ROs with CRI experience reported minimal toxicities regardless of treatment site or RT dose. Most ROs did not alter RT dose, use prophylactic steroids, or delay starting RT from last IT infusion. Uncertainty remains about improved local control outcomes and abscopal responses from CRI, yet there is a perception that concurrent SBRT offers better outcomes than palliative RT.

The effect of early versus delayed radiation therapy on length of hospital stay in the palliative setting.

Radiation therapy (RT) can offer timely and effective treatment to oncology patients in the palliative setting. To date, there is sparse evidence investigating temporal relationships regarding the initiation of RT and subsequent hospital stay in the inpatient palliative setting. We aimed to assess whether times between admission, consultation, and initiation of treatment effected the length of hospital stay for patients receiving palliative radiation therapy (PRT). This was a retrospective chart review of patients who received a consult for PRT from August 2014 to October 2016. All data was collected from a single community cancer center. Data including demographics, radiation treatment details, and temporal data (e.g., length of stay, time from admission to consult, etc.) were recorded. Of the 135 patients that received PRT, 60 of them were treated in the inpatient setting. The most common indications for PRT were pain (37%) and non-pain related neurologic symptoms (37%). The most common treatment sites were bone (58%), brain (22%), and lung (17%). There was a significant difference in duration of hospital stay between patients who were seen by palliative radiation oncology within two days versus greater than 2 days (P=0.02); and patients who were treated within 2 days of admission versus greater than 2 days (P=0.03). Further research is needed to establish causal temporal relationships in palliative radiation oncology. However, this data suggests that early involvement of the radiation oncology team is associated with a reduced length of hospital stay.

Feasibility of reirradiation and treatment outcome in a previously irradiated territory in head-and-neck malignancies

IntroductionDespite combined modality treatment, local persistent or recurrent disease is a primary cause of treatment failure in 30–50% of patients with advanced head-and-neck cancer (HNC). The role of reirradiation is feared because of increased risk of toxicity due to the previously irradiated target volume. In the present study, we have evaluated reirradiation by image-guided intensity-modulated radiotherapy in recurrent and second primary HNCs and its outcome.Materials and methodsIn all, 24 patients with recurrence or second primary tumors in HNC were included in the study conducted between January 2009 to August 2014. All patients were treated by the image-guided intensity-modulated radiotherapy technique. The most common site of recurrence/second primary was oral tongue. The time interval between initial radiotherapy and reirradiation ranged from 8 months to 17 years.Statistical analysis usedThe association between qualitative variables was tested using the χ2-test. Statistical significance was interpreted using an arbitrary cut-off of P=0.05. Kaplan–Meier Survival graph was plotted to depict the survival pattern of the study patients.ResultsThe planning target volume volume of reirradiation ranged from 26.72 to 469.32 ml (median: 118.71 ml). Toxicity was more in patients receiving concurrent chemoradiation and in patients with less interval time between reirradiation. Out of the 24 patients, nine were no evidence of disease, eight patients expired (five disease progression, two comorbidities, and one due to hematemesis after the development of third primary), two recurred, one developed distant metastases, and four were lost to follow-up.ConclusionSurgical resection, with or without reirradiaton, provides the highest likelihood for successful salvage in locoregional (LR) recurrences in HNCs. Patients reirradiated after a long time from initial irradiation have better tolerance.

Spinal Ewing Sarcoma Debuting with Cord Compression: Have We Discovered the Thread of Ariadne?

Ewing's sarcoma (ES) of the spine with cord or radicular compression as an initial sign is infrequent. It is unclear, in alleviating a neurological deficit, whether decompressive laminectomy is preferred over chemotherapy. Herein, a literature review of the treatment approaches to the primary or metastatic ES of the spine has been performed. Collected data included clinical features of the patients, treatment, and outcome. There are reported 69 cases with initial presentation of cord or radicular compression of spinal cord, arising from primary or metastatic ES, treated either with initial chemotherapy and/or radiotherapy (RT) (33.33%, n=23), or decompressive surgery (66.66%, n=46). The median age at diagnosis was 17.95 years old (range=0.06-60), and 38 patients (55.07%) were male. Eighteen (78.26%) were initially treated with chemotherapy combined with RT, whereas 3 (13.04%) were managed with RT alone. One patient (4.35%) received only corticosteroids, while there are not available data for the treatment of another one (4.35%). The remaining 46 patients (66.66%) were initially treated with decompressive surgery. Among them, 40 (57.97%) received postoperative chemotherapy, RT or combined modality therapy, whereas 6 patients (8.69%) were not treated adjuvantly. Sixteen out of 23 patients (69.6%) treated with systemic therapy, and 37 from 46 (80.43%) of those managed with decompressive laminectomy were still alive at a mean follow-up period of 2.11 years (range=0.16-6) and 3.45 years (range=0.16-26.08), respectively. To summarize, spinal resection and reconstruction followed by adjuvant treatment reduce the risk of local recurrence, and improve long-term survival. However, ES of the spine is not a distinct clinical entity and can be either managed with chemotherapy and/or RT, similarly to other localization.

Mutational analysis of uterine cervical cancer that survived multiple rounds of radiotherapy

Radiotherapy is an essential component of cancer therapy. Despite advances in cancer genomics, the mutation signatures of radioresistant tumors have not yet been fully elucidated. To address this issue, we analyzed a unique set of clinical specimens from a uterine cervical cancer that repeatedly locally recurred after multiple rounds of radiotherapy. Exon sequencing of 409 cancer-related genes in the treatment-naïve tumor and the tumors that recurred after initial and secondary radiotherapy identified (i) activating mutations in PIK3CA and KRAS, and putative inactivating mutations in SMAD4, as trunk mutation signatures that persisted over the clinical course; and (ii) mutations in KMT2A, TET1, and NLRP1 as acquired mutation signatures observed only in recurrent tumors after radiotherapy. Comprehensive mining of published in vitro genomics data pertaining to radiosensitivity revealed that simultaneous mutations in KRAS and SMAD4, which have not been described previously in uterine cervical cancer, are associated with cancer cell radioresistance. The association between this mutation signature and radioresistance was validated by isogenic cell-based experiments. These results provide proof-of-principle for the analytical pipeline employed in this study, which explores clinically relevant mutation signatures for radioresistance, and demonstrate that this approach is worth pursuing with larger cohorts in the future.

Can Initial Radiotherapy Improve Survival With Prostate Cancer?

Can Initial Radiotherapy Improve Survival With Prostate Cancer?

Radionécrose après radiothérapie stéréotaxique d’une métastase cérébrale de 3 cm : la technique peut-elle améliorer les résultats dosimétriques ?

Stereotactic radiotherapy is a major issue in the management of brain metastases. Radionecrosis is a major concern, especially for large lesions. Optimizing dosimetric parameters is essential to allow optimal local control rate while minimizing potential toxicity. We report the case of a 30-mm brain metastases treated with stereotactic radiotherapy after initial whole brain radiotherapy, complicated with symptomatic radionecrosis. A dose of 24Gy in three fractions on the 80% isodose were delivered using a dynamic conformal arc technique (Novalis TX®). We realized a dosimetric comparison with: (i) optimization of initial conformal arc plan, (ii) volumetric modulated arctherapy with coplanar arcs and (iii) volumetric modulated arctherapy with coplanar and non-coplanar arcs. The optimal dose planning in terms of planning target volume coverage (99.2%) and normal brain sparing (V24Gy=0.4cm3, V18Gy=6.5cm3, V10Gy=25.4cm3, V5=83.9cm3) was obtained with volumetric modulated arctherapy with coplanar and non-coplanar arcs. Volumetric modulated arctherapy-based stereotactic irradiation with coplanar and non-coplonar arcs seems an interesting option for the treatment of large brain metastases to optimize dosimetric parameters.

A neuropathic pain component as a predictor of improvement in pain interference after radiotherapy for painful tumors: A secondary analysis of a prospective observational study

Background and purposeWe previously demonstrated that patients with a tumor-related neuropathic pain component were more likely to experience a pain response after radiotherapy (RT) than those without. It is unknown whether the presence of a neuropathic component also favorably influences pain interference. In a secondary analysis of our previous prospective observational study, we investigated if the presence of a neuropathic component of the index pain caused by the irradiated tumors predicts greater reduction in pain interference. Material and methodsFor patients scheduled for RT for painful tumors, Brief Pain Inventory data were collected at initiation of RT and 1, 2, and 3 months thereafter. Multivariable linear regression analyses were performed to investigate the effects of the presence of a neuropathic component on the changes in pain interference scores (i.e., follow-up minus baseline). We used 10 covariates as potential confounders. ResultsOf the 302 analyzable patients, 93 (31%) were diagnosed as having a neuropathic component of the index pain. Multivariable linear regression analyses revealed that all the point estimates of regression coefficients at 1-, 2-, and 3-month follow-up were negative values; some were statistically significant. At 2-month follow-up, patients with a neuropathic component experienced greater reductions in their pain interference scores for walking ability (p = 0.048), normal work (p = 0.021), sleep (p = 0.001), and enjoyment of life (p = 0.010) than those without it. ConclusionsThe presence of a neuropathic pain component predicted a greater reduction in pain interference after RT. Patients with neuropathic tumor-related pain should be offered the option of receiving palliative RT.