Start Of Radiotherapy Research Articles

Radiation Retinopathy: Detection and Management Strategies.

A gradual shift in trend from primary enucleation to globe salvaging radiation therapy for the management of ocular tumors has resulted in the rise of several post-treatment ocular complications including radiation retinopathy. Radiation retinopathy is a chronic, progressive, and occlusive vasculopathy that can manifest anytime between 1 month to 15 years after starting radiation therapy. The aim of treatment in most of these cases is to prevent further vision loss. Treatment options such as laser photocoagulation, anti-vascular endothelial growth factor and intraviral steroids have been described. However, despite several advances in diagnostic and therapeutic modalities, a significant proportion of eyes with radiation retinopathy eventually go blind. This review summarises some of the clinical features, investigative modalities, and recent therapeutic strategies used in the management of radiation retinopathy.

Impact of adjuvant breast radiotherapy on patient-reported fatigue.

Breast cancer patients receiving adjuvant radiotherapy (RT) benefit from local control. However, RT can give rise to increased fatigue, lowering quality of life. The aim of this study was to prospectively identify trends and risk factors in patient-reported fatigue associated with breast RT. Patients were assessed using the Edmonton Symptom Assessment Scale (ESAS) before, once per week during RT, up to 6weeks after RT completion, and 1-3months post RT. Patients were included in the analysis if the ESAS was completed before, at least once during, and at least once after RT. A total of 651 patients were included. Fatigue scores increased significantly during weeks 1-3 (p < 0.001) and weeks 5-6 (p < 0.0001) during RT compared to baseline. After RT completion, fatigue scores did not change significantly compared to baseline. Mastectomy patients who received previous chemotherapy experienced significantly more fatigue compared to mastectomy patients without previous chemotherapy (p = 0.0002). Patients less than 50 (p = 0.002), 50-59 (p = 0.007), or 60-69 (p = 0.048) years of age at RT start were more likely to have higher proportions of moderate or severe fatigue compared to patients ≥ 70years of age. Fatigue associated with breast irradiation increased up to 6weeks during RT and returned to near baseline scores at 1-3months post treatment. Given that fatigue was significant in mastectomy patients, further research is needed to reduce fatigue among this cohort, especially those who have received previous chemotherapy and younger patients who are receiving breast RT.

Multifocal high-grade glioma radiotherapy safety and efficacy

BackgroundMultifocal manifestation of high-grade glioma is a rare disease with very unfavourable prognosis. The pathogenesis of multifocal glioma and pathophysiological differences to unifocal glioma are not fully understood. The optimal treatment of patients suffering from multifocal high-grade glioma is not defined in the current guidelines, therefore individual case series may be helpful as guidance for clinical decision-making.MethodsPatients with multifocal high-grade glioma treated with conventionally fractionated radiation therapy (RT) in our institution with or without concomitant chemotherapy between April 2011 and April 2019 were retrospectively analysed. Multifocality was neuroradiologically assessed and defined as at least two independent contrast-enhancing foci in the MRI T1 contrast-enhanced sequence. IDH mutational status and MGMT methylation status were assessed from histopathology records. GTV, PTV as well as the V30Gy, V45Gy and D2% volumes of the brain were analysed. Overall and progression-free survival were calculated from the diagnosis until death and from start of radiation therapy until diagnosis of progression of disease in MRI for all patients.Results20 multifocal glioma cases (18 IDH wild-type glioblastoma cases, one diffuse astrocytic glioma, IDH wild-type case with molecular features of glioblastoma and one anaplastic astrocytoma, IDH wild-type case) were included into the analysis. Resection was performed in two cases and stereotactic biopsy only in 18 cases before the start of radiation therapy. At the start of radiation therapy patients were 61 years old in median (range 42–84 years). Histopathological examination showed IDH wild-type in all cases and MGMT promotor methylation in 11 cases (55%). Prescription schedules were 60 Gy (2 Gy × 30), 59.4 Gy (1.8 Gy × 33), 55 Gy (2.2 Gy × 25) and 50 Gy (2.5 Gy × 20) in 15, three, one and one cases, respectively. Concomitant temozolomide chemotherapy was applied in 16 cases, combined temozolomide/lomustine chemotherapy was applied in one case and concomitant bevacizumab therapy in one case. Median number of GTVs was three. Median volume of the sum of the GTVs was 26 cm3. Median volume of the PTV was 425.7 cm3 and median PTV to brain ratio 32.8 percent. Median D2% of the brain was 61.5 Gy (range 51.2–62.7) and median V30Gy and V45 of the brain were 59.9 percent (range 33–79.7) and 40.7 percent (range 14.9–64.1), respectively. Median survival was eight months (95% KI 3.6–12.4 months) and median progression free survival after initiation of RT five months (95% CI 2.8–7.2 months). Grade 2 toxicities were detected in eight cases and grade 3 toxicities in four cases consisting of increasing edema in three cases and one new-onset seizure. One grade 4 toxicity was detected, which was febrile neutropenia related to concomitant chemotherapy.ConclusionConventionally fractionated RT with concomitant chemotherapy could safely be applied in multifocal high-grade glioma in this case series despite large irradiation treatment fields.

Chemotherapy is a risk factor of lymphopenia before adjuvant radiotherapy in breast cancer.

BackgroundLymphopenia can decrease immune function of the host and is a known risk factor for poor prognosis in malignant tumors. Radiation induced lymphopenia was common in patients with breast cancer and was also reported to have a negative effect on long‐term outcome.AimsLymphopenia may be associated with baseline immune status before radiotherapy (RT). This study aimed to explore the rate and risk factors of lymphopenia before start of the adjuvant RT in patients with breast cancer.MethodsPatients with invasive breast cancer treated from March 2015 to February 2020 and with peripheral lymphocyte counts (PLC) available within 7 days from the beginning of RT were eligible for this study. Data were presented as mean and 95% confidence interval unless otherwise specified. The risk factors of low PLC before RT were identified using univariate and multivariable linear regressions.ResultsA total of 1012 consecutive patients met the study criteria. The mean PLC before RT commencement was 1.58*109/L (95%CI: 1.55–1.62*109/L) with 15.2% (95%CI: 13.1%–17.6%) CTCAE defined lymphopenia, rendering 12.3%, 2.6%, 0.3%, and 0% for grade 1, 2, 3 and 4 respectively. Univariate and multivariable linear regression showed prior chemotherapy was the most significant risk factor (p < .001) for low PLC, while age, menopausal status and lymph node stage were not (all ps > .05). A total of 912 (90.1%, 95%CI: 88.1%–91.9%) patients had chemotherapy before adjuvant RT in this study. In patients with HR+/HER2‐ breast cancer, 69.0% (95%CI: 63.0%–74.5%) N0 and 98.1% (95%CI: 95.1%–99.5%) N1 had also received chemotherapy.ConclusionsPatients with breast cancer might have lymphopenia from prior chemotherapy at the start of adjuvant RT which could have negative effect on long‐term outcome. It is also noted that most of the patients with HR+/HER2‐, early‐stage breast cancer were treated with aggressive chemotherapy without knowing the risk of chemotherapy induced lymphopenia. Future study on predictive or prognostic multigene assays is warranted to avoid unnecessary chemotherapy and subsequent lymphopenia in patients with low risk breast cancer.

PH-0329 Feasibility and outcome of bridging RT pre CAR-T in DLBCL in one centre with a wide referral network

Purpose or Objective CD19 CAR-T therapy is the most effective salvage treatment for relapsed/refractory DLBCL. However the manufacture of CAR-T cells takes several weeks and patients (pts) are at risk of progression during this time and usually require some form of bridging therapy to contain their disease. Radiotherapy (RT) is an attractive bridging option, as the chance of response to further conventional cytotoxic therapy is low. RT is generally delivered in the window between apheresis and infusion and requires careful scheduling. The aim of this study is to evaluate the feasibility, toxicity and early outcome of bridging RT in a cohort of pts undergoing CAR-T therapy for DLBCL. Materials and Methods This was a prospective analysis of pts receiving bridging RT since the start of CAR-T programme at our institution. We collected data on pt demographics, disease and RT details, as well as outcomes including early response, relapse, survival and toxicity. Results (Table presented.) Between April 2019 & January 2021 a total of 27 pts have received bridging RT. Of these 23 have been infused (1 not infused due to COVID19, 1 due to cardiac function & 2 pending). The CAR-T therapy was delivered in 1 Haematology Institution, but bridging RT in 9 different referring centres. Pt and disease characteristics and RT details are shown in table 1. The median time from CT planning scan to start of RT was 10 days (4-42). The median time between apheresis and start of RT was 5 days (-37-21;3 patients received RT prior to apheresis at -37,-35 &-29 days) and median time between end of RT and CAR-T infusion was 19 days (10-116). No pts were delayed due to RT toxicity. Toxicity data was available for 22 pts. 10 (45.5%) reported no toxicity. Only 1 pt had grade 3 toxicity (vomiting & diarrhoea) and RT was stopped. The most common toxicities were skin reaction (n=5) & fatigue (n=4). 25/27 (92.6%) pts underwent a PET-CT between bridging RT & infusion. In 22 (88%) pts there was response in treatment field (CMR=2, PMR=20). In 13 (59.1%) of those pts there was evidence of progressive disease (PD) outside the field, but none were prevented from receiving CAR-T infusion due to PD. With median FU of 8.8 (0.6-20.6) months from date of CAR-T infusion, 12/ 23 (52.2%) infused pts have relapsed, (2 infield, 5 out of field, 5 in both) with a local control rate of 69.6%;CMR (12;52.2%) and PMR (4;17.4%). 7 pts have died since infusion, 6 due to PD and 1 due to sepsis. Median PFS was 5.1 months (95% CI 0.0-11.9 months) and median OS 17.8 months (95% CI 12.7-22.9 months). 1 pt had infusion delayed due to COVID19 infection and died of PD. Conclusion RT was a safe and effective bridging option in this cohort of DLBCL pts pre CAR-T therapy. With close collaboration between Haematologists and Radiation Oncologists, it is possible to deliver a course of radical dose RT in the narrow window between apheresis and infusion, even across a wide geographical network. Further work is required to determine which pts benefit most from bridging RT and the optimal dose and schedule.

Should Postoperative Radiation for Long Bone Metastases Cover Part or All of the Orthopedic Hardware? Results of a Large Retrospective Analysis

PurposeFor patients with long bone metastases who undergo orthopedic stabilization surgery followed by radiotherapy (RT), it is unclear what extent of hardware coverage by the radiation field is needed for optimal tumor control. Methods and MaterialsLong bone metastases treated with surgical intervention followed by radiation between August 2011 to May 2019 from a single institution were reviewed. Local recurrence, defined as any in-bone recurrence, was identified by chart review. Accompanying demographic and treatment characteristics were recorded. Statistical analysis to evaluate factors associated with tumor recurrence included univariate analysis, multivariate analysis, and propensity score matching. ResultsAmong 138 patients with 145 long bone metastases undergoing postoperative RT with a median follow-up of 29.5 months, 36 bone metastases experienced a local recurrence. Most patients (92%) were treated with conventional RT and the median delivered dose was 30 Gy (interquarile range, 20-30 Gy). On univariate analysis, whole hardware RT field coverage and higher dose (biologically effective dose 10 ≥39 Gy) were associated with reduced local recurrence (0.44 hazard ratio [HR]; 95% confidence interval [CI], 0.22%-0.86%; P = .017; 0.5 HR; 95% CI, 0.26%-0.96%; P = .038, respectively). Covariates of time from surgery to RT start, histology of primary tumor (categorized as resistant vs sensitive), intramedullary hardware placement, reaming procedure, and margin status did not reach statistical significance. To adjust for confounding effects, we also conducted a propensity score matched analysis which confirmed that whole hardware coverage was statistically associated with a decreased risk of recurrence on the matched dataset (0.24 HR; 95% CI, 0.07%-0.84%; P = .026). ConclusionsIn this analysis of mostly patients undergoing conventional radiation, coverage of the whole hardware was associated with reduced local recurrence for patients with long bone metastases, consistent with prior reports. Investigation of approaches to further reduce local recurrence, such as preoperative stereotactic radiation, may be warranted.

Definitive radiotherapy for extracranial oligoprogressive metastatic renal cell carcinoma as a strategy to defer systemic therapy escalation.

To study whether delivering definitive radiotherapy (RT) to sites of oligoprogression in metastatic renal cell carcinoma (mRCC) enabled deferral of systemic therapy (ST) changes without compromising disease control or survival. We identified patients with mRCC who received RT to three or fewer sites of extracranial progressive disease between 2014 and 2019 at a large tertiary cancer centre. Inclusion criteria were: (1) controlled disease for ≥3 months before oligoprogression, (2) all oligoprogression sites treated with a biologically effective dose of ≥100 Gy, and (3) availability of follow-up imaging. Time-to-event end-points were calculated from the start of RT. A total of 72 patients were identified (median follow-up 22 months, 95% confidence interval [CI] 19-32 months), with oligoprogressive lesions in lung/mediastinum (n = 35), spine (n = 30), and non-spine bone (n = 5). The most common systemic therapies before oligoprogression were none (n = 33), tyrosine kinase inhibitor (n = 23), and immunotherapy (n = 13). At 1 year, the local control rate was 96% (95% CI 87-99%); progression-free survival (PFS), 52% (95% CI 40-63%); and overall survival, 91% (95% CI 82-96%). At oligoprogression, ST was escalated (n = 16), maintained (n = 49), or discontinued (n = 7), with corresponding median (95% CI) PFS intervals of 19.7 (8.2-27.2) months, 10.1 (6.9-13.2) months, and 9.8 (2.4-28.9) months, respectively. Of the 49 patients maintained on the same ST at oligoprogression, 21 did not subsequently have ST escalation. Patients with oligoprogressive mRCC treated with RT had comparable PFS regardless of ST strategy, suggesting that RT may be a viable approach for delaying ST escalation. Randomised controlled trials comparing treatment of oligoprogression with RT vs ST alone are needed.

Quantitative Changes in Skin Composition Parameters after Radiation Therapy According to Surgery Types Among Patients with Breast Cancer: A Prospective Study

BackgroundIn the current study, we sought to evaluate and compare the objective changes in biophysical parameters and patient-reported outcomes following radiation therapy (RT) in patients with breast cancer who underwent breast-conserving surgery (BCS) or modified radical mastectomy (MRM). Materials and methodsPatients older than 18 years, with stage I to III breast cancer, who were expected to receive RT were recruited between August 2015 and March 2019. Skin hydration, sebum content, pigmentation, and elasticity of the irradiated and unirradiated breast or chest wall were assessed using a noninvasive bioengineering device. Assessments were performed before the initiation of RT (T0); after the 5th (T1), 15th (T2), and 25th (T3) fractions; and 1 (T4) and 3 months (T5) after the completion of RT. Patient-reported outcomes were also evaluated using Radiation Dermatitis Assessment for Breast Cancer 11. ResultsHydration and sebum levels on the irradiated breast decreased during RT and had not returned to baseline at T5. Erythema on the irradiated breast increased two-fold between T0 and T3, and melanin levels were significantly higher than those at baseline and those of the contralateral unirradiated breast until T5 (106.0 vs. 115.8, P = .03). More than half of the patients continued to report skin color changes, dryness, and pain after RT. The erythema in the irradiated site at T1 was significantly higher in the MRM group than in the BCS group (P for interaction = .04), while there were no significant differences in the changes of the other parameters. ConclusionRT-induced changes in hydration, sebum, and melanin, and the majority of patient-reported pain, color changes, and dryness, even 3 months after the completion of treatment. There were no remarkable differences in the measurable skin parameters according to the surgery type, with the exception of erythema, which was higher in the MRM group 1 week after the start of RT.

Serum MicroRNAs as Xerostomia Biomarkers in Patients With Oropharyngeal Cancer Undergoing Radiation Therapy

Severe xerostomia is noted in the majority of patients irradiated for oropharyngeal cancer. Extracellular microRNAs (miRNAs) may serve as effective tools allowing prediction of radiation-related toxicity. The aim of this study was to create an efficient prognostic miRNA-based test for severe, patient-rated xerostomia 3 months after primary treatment. This prospective study enrolled patients with oropharyngeal cancer treated between 2016 and 2018 in 3 centers in Poland. The primary endpoint was severe (grade ≥3) xerostomia as assessed by the European Organisation for Research and Treatment of Cancer H&N-35 questionnaires. Initially, a group of 10 patients with severe xerostomia was randomly selected and matched with a comparative group of 10 patients without severe xerostomia. Samples were collected before radiation therapy, after receiving 20 Gy, and within 24 hours after treatment completion. Quantitative real-time polymerase chain reaction arrays (QIAGEN, Hilden, Germany) were used to quantify expression levels of 752 miRNAs in the serum at all timepoints. The resulting logistic-regression based model was validated in additional 60 patients: 30 with grade >3 xerostomia and 30 without. Of 152 eligible patients, we successfully recruited 111 patients. Severe xerostomia 3 months after treatment was reported by 63 patients (56.8%). Mean dose delivered to parotid glands was higher in both the exploratory and validation cohort. The model based on miR-185-5p and miR-425-5p expression levels measured before the start of radiation therapy had an area under the curve of 0.96 (95% confidence interval, 0.88-1.00). The model based on the same miRNAs remained robust when parameters were measured after 20 Gy (area under the curve 0.90; 95% confidence interval, 0.75-1.00). These results were confirmed in the validation group. In the validation group, preradiation therapy model application yielded 73.3% sensitivity and 80.0% specificity. In the samples taken after 20 Gy, the same 2 miRNAs yielded 67.7% sensitivity and 72.4% specificity. The model including pretreatment miR-185-5p and miR-425-5p levels together with mean parotid dose yielded 90.0% sensitivity and 80.0% specificity. In the validation cohort, this model yielded 80.6% sensitivity and 55.2% specificity. The model based on miRNA levels measured after 20 Gy and mean parotid dose had 80.0% sensitivity and 100% specificity in the exploratory group. In the validation cohort its performance fell to 71.0% sensitivity and 58.6% specificity. Serum expression levels of miR-425-5p and miR-185-5p measured before the start of radiation therapy or during therapy (after 20 Gy) had significant prognostic value for the occurrence of severe xerostomia 3 months after treatment completion. The variability explained by miRNAs appears to be, at least partially, independent from that related to the dosimetric data.

Acute and Late Toxicities of Patients Infected with SARS-CoV-2 and Treated for Cancer with Radiation Therapy During the COVID-19 Pandemic

Purpose This study aimed to assess the risk of acute and late radiation-induced toxicity in patients with COVID-19. Material and methods All the patients irradiated in Institut Curie from March to July 2020 were included if the first symptoms related to COVID-19 occurred no more than two months before the start of radiation therapy (RT) or 15 days after the end of RT. Results Twenty-nine patients were included in this analysis. Twenty-five patients had no co-morbidities (86.2%), including morbid obesity. The diagnosis of COVID-19 infection was based on a positive SARS-CoV-2 RNA test for 18 patients (62.1%), a positive serology test for three patients (10.3%), and/or radiologic findings for 12 patients (41.4%). Three patients with symptoms highly suggestive of COVID-19 were included, although they had negative biologic tests and did not have a chest CT scan. Median time from the diagnosis of COVID-19 to the onset of RT was 5.5 days. Modification of RT course due to COVID-19 status was observed in 15 patients, including four for whom RT was definitively stopped. Six patients needed hospitalization for hypoxemic lung disease requiring intensive care. The majority of patients did not experience severe (> grade 2) acute toxicity. After a median follow-up of 6 months (IQR, 1 – 9 months), none of the patients had unusual clinical or radiological late toxicities. Conclusion The observed acute and late toxicities were ultimately similar to those observed in a population not infected with COVID-19. These results do not prompt modification of standard RT protocols for irradiation of COVID-19 patients.

Preclinical modeling in glioblastoma patient-derived xenograft (GBM PDX) xenografts to guide clinical development of lisavanbulin-a novel tumor checkpoint controller targeting microtubules.

Glioblastoma (GBM) is an incurable disease with few approved therapeutic interventions. Radiation therapy (RT) and temozolomide (TMZ) remain the standards of care. The efficacy and optimal deployment schedule of the orally bioavailable small-molecule tumor checkpoint controller lisavanbulin alone, and in combination with, standards of care were assessed using a panel of IDH-wildtype GBM patient-derived xenografts. Mice bearing intracranial tumors received lisavanbulin +/-RT +/-TMZ and followed for survival. Lisavanbulin concentrations in plasma and brain were determined by liquid chromatography with tandem mass spectrometry, while flow cytometry was used for cell cycle analysis. Lisavanbulin monotherapy showed significant benefit (P < .01) in 9 of 14 PDXs tested (median survival extension 9%-84%) and brain-to-plasma ratios of 1.3 and 1.6 at 2- and 6-hours postdose, respectively, validating previous data suggesting significant exposure in the brain. Prolonged lisavanbulin dosing from RT start until moribund was required for maximal benefit (GBM6: median survival lisavanbulin/RT 90 vs. RT alone 69 days, P = .0001; GBM150: lisavanbulin/RT 143 days vs. RT alone 73 days, P = .06). Similar observations were seen with RT/TMZ combinations (GBM39: RT/TMZ/lisavanbulin 502 days vs. RT/TMZ 249 days, P = .0001; GBM26: RT/TMZ/lisavanbulin 172 days vs. RT/TMZ 121 days, P = .04). Immunohistochemical analyses showed a significant increase in phospho-histone H3 with lisavanbulin treatment (P = .01). Lisavanbulin demonstrated excellent brain penetration, significant extension of survival alone or in RT or RT/TMZ combinations, and was associated with mitotic arrest. These data provide a strong clinical rationale for testing lisavanbulin in combination with RT or RT/TMZ in GBM patients.

Early and Midtreatment Mortality in Palliative Radiotherapy: Emphasizing Patient Selection in High-Quality End-of-Life Care.

Palliative radiotherapy (RT) is effective, but some patients die during treatment or too soon afterward to experience benefit. This study investigates end-of-life RT patterns to inform shared decision-making and facilitate treatment consistent with palliative goals. All patients who died ≤6 months after initiating palliative RT at an academic cancer center between 2015 and 2018 were identified. Associations with time-to-death, early mortality (≤30 days), and midtreatment mortality were analyzed. In total, 1,620 patients died ≤6 months from palliative RT initiation, including 574 (34%) deaths at ≤30 days and 222 (14%) midtreatment. Median survival was 43 days from RT start (95% CI, 41-45) and varied by site (P<.001), ranging from 36 (head and neck) to 53 days (dermal/soft tissue). On multivariable analysis, earlier time-to-death was associated with osseous (hazard ratio [HR], 1.33; P<.001) and head and neck (HR, 1.45; P<.001) sites, multiple RT courses ≤6 months (HR, 1.65; P<.001), and multisite treatments (HR, 1.40; P=.008), whereas stereotactic technique (HR, 0.77; P<.001) and more recent treatment year (HR, 0.82; P<.001) were associated with longer survival. No difference in time to death was noted among patients prescribed conventional RT in 1 to 10 versus >10 fractions (median, 40 vs 47 days; P=.272), although the latter entailed longer courses. The 30-day mortality group included 335 (58%) inpatients, who were 27% more likely to die midtreatment (P=.031). On multivariable analysis, midtreatment mortality among these inpatients was associated with thoracic (odds ratio [OR], 2.95; P=.002) and central nervous system (CNS; OR, 2.44; P=.002) indications, >5-fraction courses (OR, 3.27; P<.001), and performance status of 3 to 4 (OR, 1.63; P=.050). Conversely, palliative/supportive care consultation was associated with decreased midtreatment mortality (OR, 0.60; P=.045). Earlier referrals and hypofractionated courses (≤5-10 treatments) should be routinely considered for palliative RT indications, given the short life expectancies of patients at this stage in their disease course. Providers should exercise caution for emergent thoracic and CNS indications among inpatients with poor prognoses due to high midtreatment mortality.

Clinical outcome and toxicity of radiotherapy for inferior vena cava tumor thrombus in HCC patients: A retrospective study.

Hepatocellular carcinoma (HCC) involving the inferior vena cava rarely occurs, but its prognosis is extremely poor, with no established treatment to date. This study aimed to analyze the clinical outcome and toxicity of radiotherapy (RT) targeting inferior vena cava tumor thrombus (IVCTT) in HCC patients.From November 2011 to July 2020, medical record of 19 HCC patients who were treated with RT for IVCTT was retrospectively reviewed. RT was delivered using 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and stereotactic body radiation therapy. The median radiation dose was 50 Gy (range, 45–55.8 Gy) for intensity-modulated radiation therapy and three-dimensional conformal radiotherapy. Stereotactic body radiation therapy was performed in 5 patients, for a total of 32 Gy in 4 fractions.The median follow-up duration was 8.1 months (range, 3.3–26.5 months). The median overall survival was 9.4 months (range, 3.7–26.5 months), and the 1-year overall survival rate was 37.1%. Eight of 19 patients (42.1%) had extrahepatic metastasis at the start of RT. Six of 11 patients (54.5%) who did not have extrahepatic metastasis at the start of RT showed extrahepatic metastasis after RT. The major cause of death was progression of extrahepatic metastasis (11 patients, 57.9%). The overall response rate of IVCTT for RT was 84.2%, and the local control rate at the time of the last follow-up was 89.4%. After RT, the most common first progression site was the lungs (9 patients, 47.4%). Most toxicities were grade 1 to 2 gastrointestinal (26.3%) and liver enzyme elevation (68.4%). Three patients occurred pulmonary embolism after RT later than 5 months after.RT is a feasible and safe local therapy for IVCTT, with favorable tumor control and acceptable toxicity. Extrahepatic metastasis is the major progression pattern and a leading cause of death in patients treated with RT. The combination of effective systemic therapy with RT may have to be considered.

Does kV Image Guidance for Bone Metastases Improve Pain Control?

Purpose/ObjectivesDespite its widespread availability, the use of kilovoltage (kV) image guidance is often related to factors such as perceived adequacy of clinical patient setup and individual practice patterns. We sought to determine whether kV image guidance in the treatment of painful bone metastases would improve therapeutic efficacy.Materials/MethodsUnder an Institutional Review Board approved protocol, hospital records of 164 patients having received radiation therapy to 257 individual painful osseous metastases were retrospectively reviewed. Marginal logistic regression analyses using the generalized estimating equation (GEE) approach were used to investigate potential associations between pain reduction and several patient, disease, and treatment related variables. Correlation of kV image guidance with pain reduction was analyzed by univariate and multivariate GEE logistic regression analysis.ResultsMedian time to pain reduction was 3 days (range 0~109 days) from the start of radiation therapy. Pain reduction ≥ 50% was noted in 196 (77%) metastatic lesions with 136 (53%) demonstrating complete pain relief. Patients with metastatic lesions from non-small cell lung cancer experienced less pain relief (p = 0.007). Disease extension outside of bone was a negative predictor for pain reduction (p = 0.02). On univariate and multivariate logistic regression, kV image guidance demonstrated a statistically significant correlation with improved pain control in cases involving treatment of the lower extremities (p = 0.03) and those with fewer treatment fractions (p = 0.01), particularly in the setting of extra-osseous disease extension (p = 0.003).ConclusionsKilovoltage image guidance in the treatment of painful bone metastases may offer greater pain control through improved patient setup, particularly for patients with tumors of the lower extremities, extraosseous disease extension, and fewer treatment fractions.

Time-Course of Salivary Metabolomic Profiles during Radiation Therapy for Head and Neck Cancer.

Oral mucositis (OM) is one of the most frequently observed adverse oral events in radiation therapy for patients with head and neck cancer. Thus, objective evaluation of OM severity is needed for early and timely intervention. Here, we analyzed the time-course of salivary metabolomic profiles during the radiation therapy. The severity of OM (National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v3.0) of nine patients with head and neck cancer was evaluated. Partial least squares regression-discriminant analysis, using samples collected before radiation therapy, showed that histidine and tyrosine highly discriminated high-grade OM from low-grade OM before the start of radiation therapy (significant difference, p = 0.048 for both metabolites). Further, the pretreatment concentrations of gamma-aminobutyric acid and 2-aminobutyric acids were higher in the high-grade OM group. Although further validations are still necessary, this study showed potentially associated metabolites with worse radiotherapy-related OM among patients with head and neck cancer.

Overall survival after initial radiotherapy for brain metastases; a population based study of 2140 patients with non-small cell lung cancer

Background Brain metastases (BM) occur in about 30% of all patients with non-small cell lung cancer (NSCLC). BM treatment guidelines recommend more frequent use of stereotactic radiotherapy (SRT). Overall, studies report no difference in overall survival (OS) comparing SRT to whole-brain radiotherapy (WBRT). We examined survival after radiotherapy for BM in a population-based sample from the South-Eastern Norway Regional Health Authority treated 2006-2018. Methods We reviewed electronic medical records of 2140 NSCLC patients treated with SRT or WBRT for BM from 2006–2018. Overall survival (OS) was compared to predicted survival according to the prognostic systems DS-GPA and Lung-molGPA. Results Use of SRT increased during the period, from 19% (2006–2014) to 45% (2015–2018). Median OS for all patients was 3.0 months, increasing from 2.0 (2006) to 4.0 (2018). Median OS after SRT was 7.0 months (n = 435) and 3.0 months after WBRT (n = 1705). Twenty-seven percent of SRT patients and 50% of WBRT patients died within 90 days after start of RT. Age ≥70, male sex, KPS ≤70, non-adenocarcinoma histology, ECM present, multiple BM, and WBRT were associated with shorter survival (p < .001). Actual mOS corresponded best with predicted mOS by DS-GPA and Lung-molGPA for the SRT group. Conclusion Overall survival after radiotherapy (RT) for BM improved during the study period, but only for patients treated with SRT. Survival after WBRT remains poor; its use should be questioned. DS-GPA and Lung-molGPA seem most useful in predicting prognosis considered for SRT.

Preliminary results of phase 2 trial of preoperative image guided intensity modulated proton radiation therapy (IMPT) with simultaneously integrated boost (SIB) to the high-risk margin for retroperitoneal sarcomas (RPS).

11550 Background: RPS often have local recurrence (LR) after surgery. Preoperative radiation (RT) to 50.4 Gy can reduce LR risk but is not uniformly effective, especially after (+) margin resections. Therefore, we conducted a multi-institutional, prospective Phase II study to assess efficacy and tolerability of preop IMPT with selective dose escalation to 63 GyRBE to the posterior RPS margin (clinical target volume [CTV] 2) at high risk for (+) margins to further reduce the risk of LR. This dose was tolerable in a prior phase I study (DeLaney T et al, 2017, PMID:28740917). Methods: Primary RPS patients (pts) &gt;18 years received preop IMPT, 50.4 GyRBE in 28 fractions (fx) of 1.8 GyRBE to CTV1 (tumor plus adjacent tissue at risk of subclinical disease) with SIB to CTV2 to 63.0 GyRBE in 28 fx of 2.25 GyRBE. Pts with high-grade tumors could get chemotherapy(CTX) prior to IMPT. To avoid treatment delay, 11 fx of IMRT x-rays could be substituted for IMPT. Pts had restaging and surgery 4-8 weeks after IMPT. Primary study endpoint was local tumor control. Secondary endpoints included clinical and pathologic response, surgical margin status, and disease-free and overall survival. Results: We accrued 60 pts from January 2016 to February 2021. Histology: 35 liposarcoma(LPS) (19 dediff and 16 well diff), 22 leiomyosarcoma(LMS), and 3 undifferentiated pleomorphic sarcoma. IMPT was delivered per protocol in all pts. 51 pts have had surgery, 5 are awaiting surgery, and 4 had no surgery due to metastases(DM) on preop imaging. 22 pts had (+) margins. 2 pts had &gt; 75% necrosis. With 23-month median (range 1-52 months) follow-up after start of RT, there were two LRs. A dediff LPS pt had a well diff LPS LR 26 months postop, resected, and is disease-free. A renal vein/IVC LMS pt treated with CTX and IMPT had LR and DM 4 months postop and died from disease. Surgical Clavien-Dindo morbidity scores: 0(21), 1(9), 2(8), 3a (4), 3b(4), 4a(2), 4(b)1, 5(2); the periop deaths were from sepsis(pneumonia) and duodenal ulcer. The grade 3-4 periop morbidity included abscess(3), treated by catheter(2) or operative(1) drainage, prolonged hospital stays (2 pts with IVC LMS), small bowel obstruction (1), and late sigmoid colon anastomotic failure (1). Readmissions for lymphopenia(1), pneumoperitoneum (1), and volume overload (1). One late neuropathy was seen in a Type II diabetic pt with transient postop weakness after femoral nerve dissection who later had significant lower extremity weakness 3.75 years postop. Study was amended to reduce IMPT dose in diabetic pts. Conclusions: Preoperative IMPT with selective dose escalation to 63 GyRBE to the high risk posterior RPS margin is feasible. Early local control results with this approach appear promising. Some peri-operative morbidity was noted but appears to be in the expected range for RPS resections. Clinical trial information: NCT01659203.

The impact of radiotherapy on the quality of life in patients with early-stage clinical head and neck cancer.

Radiotherapy (RT) for patients with head and neck squamous cell carcinoma (HNSCC) affects vital functions related to the irradiation volume of the head and neck region and, in addition, has a negative impact on social functioning, thereby significantly impairing patients' quality of life (QoL). The aim of this study was to assess changes in the quality of life in patients with head and neck cancer treated with curative RT at 12 months after completion of RT. The aim of this study was to assess the differences between the baseline QoL of patients with early clinical stage HNSCC and at 12 months after curative/radical RT. The prospective clinical study included 92 patients in good general condition (ECOG 0-1 - Eastern Cooperative Oncology Group performance status), without regional or distant metastases, diagnosed with pathomorphologically confirmed early-stage head and neck squamous cell carcinoma treated with definitive RT. All patients participating in the study signed an informed consent form. QoL was assessed using the standard EORTC QLQ-C30 and QLQH&amp;N35 questionnaires. In addition, information on clinical aspects and data relating to socio-demographic factors were obtained from each patient. Statistical analysis was performed using a statistical package (SPSS 17.0). T-test was used for dependent and independent samples. A general linear model was used for repeated measures. Patients' QoL deteriorated significantly after definitive RT. Worse QoL Core-30 scores in patients 12 months after the end of RT, compared with baseline QoL, before the start of RT, were observed in domains such as physical performance, fulfillment of life roles, cognitive functioning, loss of appetite, fatigue and constipation. For the QLQ-H&amp;N35 questionnaires, patients 12 months after the end of RT reported problems in relation to aspects of life such as senses, mouth opening, dry mouth, thick saliva, pain, and weight loss. RT, even in early clinical stage head and neck cancer, has a negative impact on QoL, despite modern treatment techniques.

Separation surgery for metastatic epidural spinal cord compression: comparison of a minimally invasive versus open approach.

The aim of this study was to compare outcomes of separation surgery for metastatic epidural spinal cord compression (MESCC) in patients undergoing minimally invasive surgery (MIS) versus open surgery. A retrospective study of patients undergoing MIS or standard open separation surgery for MESCC between 2009 and 2019 was performed. Both groups received circumferential decompression via laminectomy and a transpedicular approach for partial corpectomy to debulk ventral epidural disease, as well as instrumented stabilization. Outcomes were compared between the two groups. There were 17 patients in the MIS group and 24 in the open surgery group. The average age of the MIS group was significantly older than the open surgery group (65.5 vs 56.6 years, p < 0.05). The preoperative Karnofsky Performance Scale score of the open group was significantly lower than that of the MIS group, with averages of 63.0% versus 75.9%, respectively (p = 0.02). This was also evidenced by the higher proportion of emergency procedures performed in the open group (9 of 24 patients vs 0 of 17 patients, p = 0.004). The average Spine Instability Neoplastic Score, number of levels fused, and operative parameters, including length of stay, were similar. The average estimated blood loss difference for the open surgery versus the MIS group (783 mL vs 430 mL, p < 0.05) was significant, although the average amount of packed red blood cells transfused was not significantly different (325 mL vs 216 mL, p = 0.39). Time until start of radiation therapy was slightly less in the MIS than the open surgery group (32.8 ± 15.6 days vs 43.1 ± 20.3 days, p = 0.069). Among patients who underwent open surgery with long-term follow-up, 20% were found to have local recurrence compared with 12.5% of patients treated with the MIS technique. No patients in either group developed hardware failure requiring revision surgery. MIS for MESCC is a safe and effective approach for decompression and stabilization compared with standard open separation surgery, and it significantly reduced blood loss during surgery. Although there was a trend toward a faster time to starting radiation treatment in the MIS group, both groups received similar postoperative radiotherapy doses, with similar rates of local recurrence and hardware failure. An increased ability to perform MIS in emergency settings as well as larger, prospective studies are needed to determine the potential benefits of MIS over standard open separation surgery.

First experience of autonomous, un-supervised treatment planning integrated in adaptive MR-guided radiotherapy and delivered to a patient with prostate cancer

Background and purposeCurrently clinical radiotherapy (RT) planning consists of a multi-step routine procedure requiring human interaction which often results in a time-consuming and fragmented process with limited robustness. Here we present an autonomous un-supervised treatment planning approach, integrated as basis for online adaptive magnetic resonance guided RT (MRgRT), which was delivered to a prostate cancer patient as a first-in-human experience. Materials and methodsFor an intermediate risk prostate cancer patient OARs and targets were automatically segmented using a deep learning-based software and logical volume operators. A baseline plan for the 1.5 T MR-Linac (20x3 Gy) was automatically generated using particle swarm optimization (PSO) without any human interaction. Plan quality was evaluated by predefined dosimetric criteria including appropriate tolerances. Online plan adaptation during clinical MRgRT was defined as first checkpoint for human interaction. ResultsOARs and targets were successfully segmented (3 min) and used for automatic plan optimization (300 min). The autonomous generated plan satisfied 12/16 dosimetric criteria, however all remained within tolerance. Without prior human validation, this baseline plan was successfully used during online MRgRT plan adaptation, where 14/16 criteria were fulfilled. As postulated, human interaction was necessary only during plan adaptation. ConclusionAutonomous, un-supervised data preparation and treatment planning was first-in-human shown to be feasible for adaptive MRgRT and successfully applied. The checkpoint for first human intervention was at the time of online MRgRT plan adaptation. Autonomous planning reduced the time delay between simulation and start of RT and may thus allow for real-time MRgRT applications in the future.