Initial Radiotherapy Research Articles

English

BACKGROUND Establishing the usefulness of adaptive radiotherapy in our setting with limited data might help to ensure better conformity and reduce treatment related morbidity. Hence we conducted this study to elicit the benefit of adaptive radiotherapy with helical tomotherapy. METHODS This is a prospective study conducted among 25 head and neck cancer patients undergoing radiotherapy with helical tomotherapy. All patients underwent initial radiation therapy treatment planning simulation positron emission tomography computed tomography (PET CT/ CT scan) [CT-1], followed by repeat PET CT/ CT scan at 4th - 5th week of radiotherapy [CT-2]. Planning for full intended dose [66 Gy - 70 Gy] was done on both the scans, keeping the radiation therapy planning parameters same. Changes in the volume of the clinical target volumes (CTV), changes in the volume and dose to spinal cord, bilateral parotids, and mandible were compared. A p - value of < 0.05 was considered for statistical significance. RESULTS A significant reduction in the volumes of tumour - CTV-1 [CT-1 v/s CT-2: 166.82 cc v/s. 150.63 cc] and of lymph nodal region - CTV-2 [CT-1 v/s CT-2: 260.29 cc v/s 228.00 cc], contra lateral parotid gland [CT-1 v/s CT-2: 33.00 cc v/s 18.72 cc] were observed (P < 0.05). The mean doses received by contra lateral parotid gland [CT-1 v/s. CT-2: 23.14 Gy v/s 21.26 Gy] were significantly lesser in the CT2 scans (P < 0.05). The mean maximum doses were also significantly lesser to the mandible and spinal cord i.e., CT-1 v/s. CT-2: 68.528 Gy v/s 67.39 Gy and 39.45 Gy v/s. 37.33 Gy respectively (P < 0.05). A significant reduction in standardised uptake value (SUV), values of the primary tumour and involved lymph nodes was observed between CT-1 and CT-2. CONCLUSIONS During 4th to 5th week of radiation therapy, significant reductions in the CTVs and in dose to OARs were noted. Thus, we recommend at least one re-simulation scan and re-planning during radiation therapy, irrespective of the type of technique of radiation therapy. KEYWORDS Adaptive Radiation Therapy, IMRT, Tomotherapy

A multi-center prospective study of re-irradiation with bevacizumab and temozolomide in patients with bevacizumab refractory recurrent high-grade gliomas.

Survival is dismal for bevacizumab refractory high-grade glioma patients. We prospectively investigated the efficacy of re-irradiation, bevacizumab, and temozolomide in bevacizumab-naïve and bevacizumab-exposed recurrent high-grade glioma, without volume limitations, in a single arm trial. Recurrent high-grade glioma patients were stratified based on WHO grade (4 vs. < 4) and prior exposure to bevacizumab (yes vs. no). Eligible patients received radiation using a simultaneous integrated boost technique (55Gy to enhancing disease, 45Gy to non-enhancing disease in 25 fractions) with bevacizumab 10mg/kg every 2 weeks IV and temozolomide 75mg/m2 daily followed by maintenance bevacizumab 10mg/kg every 2 weeks and temozolomide 50mg/m2 daily for 6 weeks then a 2 week holiday until progression. Primary endpoint was overall survival. Quality of life was studied using FACT-Br and FACT-fatigue scales. Fifty-four patients were enrolled. The majority (n = 36, 67%) were bevacizumab pre-exposed GBM. Median OS for all patients was 8.5 months and 7.9 months for the bevacizumab pre-exposed GBM group. Patients ≥ 36 months from initial radiation had a median OS of 13.3 months compared to 7.5 months for those irradiated < 36 months earlier (p < 0.01). FACT-Br and FACT-Fatigue scores initially declined during radiation but returned to pretreatment baseline. Treatment was well tolerated with 5 patients experiencing > grade 3 lymphopenia and 2 with > grade 3 thrombocytopenia. No radiographic or clinical radiation necrosis occurred. Re-irradiation with bevacizumab and temozolomide is a safe and feasible salvage treatment for patients with large volume bevacizumab-refractory high-grade glioma. Patients further from their initial radiotherapy may derive greater benefit with this regimen.

Prolonged Time of Lung Collapse Associated With Decreased Recovery of Functional Lung Following Palliative Radiotherapy

<h3>Purpose/Objective(s)</h3> Bronchial obstruction leading to lung collapse from primary lung or metastatic tumors is a common urgent consult to radiation oncology. Palliative chest radiotherapy (RT) can reduce the risk of progression of endobronchial or extrabronchial disease can be utilized alone or in combination with bronchial stenting to re-open existing collapsed lung. The ability to re-open collapsed lung following RT is likely multi-factorial with time since lung collapse long thought as an important predictor of reversibility. In this study, we sought to quantify the time-dependency of recovery of functional lung volume in patients with partial or complete lung collapse using a CT-based imaging metric highly correlated with lung function. <h3>Materials/Methods</h3> Patients with primary lung or metastatic tumors who received palliative chest RT due to segmental, lobar or whole lung collapse who additionally had follow-up CT imaging of the chest were identified from the institutional electronic health record. Total lung volumes on simulation and follow-up chest CTs were manually segmented using a commercially available software. To evaluate functional lung volume, a subthreshold function was applied to the image sets to determine volume of lung with attenuation of -950 to -701 HU. An estimate of time since initiation of lung collapse was determined by review of clinical records and imaging. <h3>Results</h3> A total of 25 evaluable patients were identified with non-small cell lung cancer (NSCLC) being the predominant histology observed (19/25, 76%). The median time of collapse before initiation of RT was 11 days (range = 3-57). The median dose received was 20 Gy in 5 fractions (range = 8 Gy/1 fx to 30 Gy/10 fx). The mean change in total lung volume was 1090 cc with mean change in functional lung volume of 1006 cc. Overall, a 92% increase in functional lung volume was observed following chest RT in this cohort. A linear trend toward decreasing recovery of functional lung was observed with more prolonged lung collapse (<i>P</i> = 0.074). Patients with estimated time of lung collapse of ≤14 days had higher mean recovery of functional lung (113%) compared with those with lung collapse > 14 days (55%) (<i>P</i> = 0.040). <h3>Conclusion</h3> Early initiation of palliative RT following lung collapse may lead to greater recovery of functional lung volume, which may confer a survival benefit/decrease hospitalization rates/improve fitness for systemic therapy. Improvements in targeted therapies are leading to more durable systemic responses potentially increasing the importance of timely chest RT for patients with existing or pending lung collapse as a bridge during acute thoracic events.

Long Term Follow-Up of a Single-Institution Prospective Study

The administration of concurrent chemotherapy and radiotherapy (RT) is advantageous as it addresses both the local disease, potential sites of metastatic disease and delivering both together may provide a synergistic effect resulting in better tumor control. The purpose of this analysis was to report the long-term overall survival, disease free survival and local control from our institutional study of the efficacy of post-operative doxorubicin/cyclophosphamide followed by concurrent paclitaxel and reduced dose radiotherapy in patients with node-positive breast cancer.44 women with Stage II or III pathologically confirmed node-positive breast cancer were enrolled in a Phase II, prospective, single-arm trial from June 2000 through December 2004. All patients received breast-conserving surgery and 4 cycles of doxorubicin (60 mg/m2)/cyclophosphamide (600 mg/m2) followed by 4 cycles of paclitaxel (175 mg/m2) which was delivered every 3 weeks. RT was concurrent with the first 2 cycles of paclitaxel. The breast received 39.6 Gy in 22 fractions with a tumor bed boost of 14 Gy in 7 fractions. Regional lymph nodes were treated, when indicated, using a dose of 45 Gy in 25 fractions. There was no inclusion of the internal mammary nodal chain. The diffusing capacity for carbon monoxide (DLCO) was measured as a means to evaluate functional lung volume. Pulmonary function tests with DLCO were obtained before and after RT, after completion of chemotherapy, and annually for 5 years. Breast cosmesis before initiation of RT was evaluated by the treating radiation oncologist, and scored using Harvard criteria. Cosmesis was scored weekly during RT, 1 month after RT, and every 3 months thereafter for 1 year.At a median follow-up of 205 months (17 yrs), overall survival is 75% and disease-free survival is 86.4%. There were 2 local recurrences yielding a local recurrence free survival of 95.5%. One of the patients with a local recurrence previously had a stage IIA (T1N1M0), grade 2 infiltrating ductal carcinoma, ER 90%, PR 50%, HER2 negative. The recurrence was stage IIA, (T1N1M0) grade 2, invasive lobular carcinoma, triple negative, considered a new primary. The two patients who experienced a local recurrence were successfully salvaged and are disease free. There were no cases of radiation pneumonitis. There was no significant change in the diffusing capacity for carbon monoxide either immediately after radiotherapy (P = 0.51) or with extended follow-up (P = 0.63) CONCLUSION: With long-term follow-up, the use of concurrent chemotherapy with low dose radiation as adjuvant treatment for node positive breast cancer has continued to demonstrate efficacy with excellent disease-free survival, overall survival and local control with acceptable toxicity.

Racial and Ethnic Health Disparities in Delay to Initiation of Intensity-Modulated Radiotherapy

The benefits of intensity-modulated radiotherapy (IMRT) over standard radiotherapy (RT), including decreased toxicity and improved quality of life, have been demonstrated in many cancer sites. Timely initiation of RT is critical, yet many factors can affect the interval to initiation of treatment (IIT). Delays may contribute to worse cancer outcomes such as increased locoregional recurrence and decreased survival. We aimed to examine racial health inequities associated with delayed initiation of IMRT.The National Cancer Database was queried to identify the ten sites with the highest total number of cancer patients treated with definitive intent IMRT. Exclusions included stage IV, age < 18, unknown insurance status, unknown race, and adjuvant or palliative intent RT. Race and ethnicity were classified as non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic, Asian, Native American/Eskimo, and Hawaiian/Pacific islander. IIT was broken into quartiles for each disease site, with the first two quartiles classified as "no delay" and the 4th quartile classified as "delayed." Multivariable logistic regression for delayed IIT was performed for each disease site using clinical and demographic covariates. Duration of IIT was compared between subgroups using two-sample t-tests.Among 350,425 patients treated with IMRT from 2004-2017, NHB and Hispanic patients were significantly more likely to have delayed IIT with IMRT for nearly all disease sites compared to NHW patients (see Table 1). IIT was significantly longer for NHB (Median 87 d [days], P < 0.001) and Hispanic patients (Median 76 d, P < 0.001) compared to NHW patients (Median 67 d). A separate analysis revealed NHB and Hispanic patients were also more likely to have delays in standard 3D conformal RT, however the median difference in IIT compared to NHW was smaller than in those receiving IMRT (NHB median 58d, Hispanic median 55d, NHW median 45d, P < 0.001).Significant racial and ethnic disparities in the likelihood and duration of treatment delay were observed. These findings raise concerns that delays in initiation of IMRT in Black and Hispanic patients may contribute to the previously documented differences in cancer outcomes. Investigating sources of these delays, including insurance authorization/denials, is urgently needed to improve timely initiation of IMRT. Table 1: Association between race/ethnicity and IIT.

Survival and Toxicity in Patients With Unresectable/Inoperable Biliary Cancers Treated with SBRT vs. Conventionally Fractionated Chemoradiation.

<h3>Purpose/Objective(s)</h3> The mainstay of treatment for unresectable/inoperable biliary cancers (UIBC) is chemotherapy (CHT) and radiotherapy (RT). We report our single institution clinical efficacy and safety in patients with UIBC treated with SBRT versus conventionally fractionated radiation (CRT). <h3>Materials/Methods</h3> Patients with UIBC treated with SBRT (n = 18) or CRT (n = 23) between 2006 and 2020 were identified. Additional management included neoadjuvant, adjuvant and/or concurrent CHT. Kaplan-Meier estimates of progression free survival (PFS), overall survival (OS) and locoregional control (LRC) were compared with log rank tests. Toxicities during treatment and follow up were based on the CTCAE v5.0. Acute toxicity was defined as adverse events < 6 months from initiation of RT. Differences by RT in patient and treatment characteristics and toxicities were assessed with Chi-square and Fisher's exact tests. Given the small sample, differences with significance of <i>P</i> < 0.10 were considered of potential clinical relevance. <h3>Results</h3> Of the 41 patients analyzed 54% were male, and 20% were non-white. CRT patients were younger than SBRT (median age 64 vs 76 yrs., <i>P</i> < 0.001). Tumor sites included 58% intrahepatic, 27% extrahepatic and 15% gallbladder. There were more > 5 cm tumors in the SBRT (51%) group than CRT (22%). The median SBRT dose was 60 Gy in 5 fractions and the median dose for CRT was 50 Gy in 25 fractions. SBRT dose was dichotomized into BED₁₀ ≥ 100 Gy and < 100 Gy. Of all patients, 29% did not receive any CHT, 24% received neoadjuvant CHT, 44% received adjuvant CHT and 51% received concurrent CHT. Overall, 26 patients died. Median follow-up of those alive was 8.2 months with no difference by RT type. The 1-yr PFS was 31.5% (95% CI 8.5-58.1) for SBRT and 18.8% (95% CI 5.9-37.3) for CRT (<i>P</i> = 0.042). Gallbladder and intrahepatic locations were associated with higher PFS compared to extrahepatic disease (<i>P</i> = 0.002). The 1-yr OS was 68.4% (95% CI 33.9-87.5) for SBRT and 67.0% (95% CI 42.7-82.8) for CRT (<i>P</i> = 0.151). BED₁₀ ≥ 100 Gy had higher OS than CRT or low dose SBRT (<i>P</i> = 0.014). Improved ECOG status was associated with higher OS (<i>P</i> = 0.044). LRC was 42.0% (95 CI 11.3-70.8) for SBRT and 26.1% (95% CI: 7.1-50.6) for CRT (<i>P</i> = 0.149). There was a trend towards improved LRC in tumors > 5 cm (<i>P</i> = 0.097). For acute toxicity, both treatments were well tolerated overall with only 1 patient with grade 3+ toxicity. 74% of CRT patients had an acute toxicity compared to 39% of SBRT patients (<i>P</i> = 0.024). There was no difference in late toxicity between the two groups. There was no grade 3+ late toxicity. <h3>Conclusion</h3> In this single-institution retrospective study, there was improved PFS in UIBC treated with SBRT. There was a trend towards improved LRC in larger tumors. Dose escalation to BED₁₀ ≥ 100 Gy in this series improved OS. SBRT was also better tolerated than CRT.

Population-Based Analysis of Outcomes for Patients With Brain Metastases From Epidermal Growth Factor Receptor Mutation Positive Non-Small Cell Lung Cancer Treated With Tyrosine Kinase Inhibitor Alone or Combined With Radiotherapy

With modern therapies, the median survival of patients with brain metastases (BrM) from non-small cell lung cancer (NSCLC) with epidermal growth factor receptor mutation (EGFRm) may exceed 1-2 years. BrM directed therapies must therefore carefully balance treatment efficacy and late toxicity. Although some tyrosine kinase inhibitors (TKI) exhibit intracranial activity, there is no level-one evidence to support up-front treatment of BrM using TKI without radiotherapy (RT). This study aimed to compare the outcomes of patients with BrM from EGFRm NSCLC treated with initial RT and TKI, versus TKI alone.All patients who received a TKI (gefitinib, erlotinib, afatinib, or osimertinib) in British Columbia for NSCLC between January 2010 to 2018 were identified in a provincial pharmacy database. Patients were then screened for pathologic diagnosis of EGFRm, and radiologic diagnosis of BrM. These patients were categorized as receiving either TKI alone or RT with TKI for treatment of their BrM. Patients who received RT were cross-referenced with a provincial RT database to determine radiotherapy prescriptions and were classified as having received whole brain (WBRT) with TKI or stereotactic RT/radiosurgery (SRS) with TKI. Patients were excluded if they discontinued TKI after RT or ever received surgery for BrM. Overall survival (OS) and intracranial progression free survival (iPFS) were calculated from the date of BrM diagnosis using Kaplan-Meier analysis. Log rank test was used for comparison between groups, and Cox proportional hazards model was used for multivariate analysis.A total of 167 patients were included for analysis with a median follow up of 45 months. Median OS was 19 months with WBRT (n = 76), 21 months with SRS (n = 45), and 6 months with TKI alone (n = 46), P < 0.01. In patients who had WBRT, iPFS was better than in those having TKI alone [HR 4.68 (2.07-10.56); P < 0.01] or SRS [HR 2.43 (1.20-4.91); P < 0.01]. On multivariate analysis: advanced age, worse performance status, presence of extracranial metastasis, greater than 10 B.M. and type of treatment (TKI alone versus RT with TKI) were associated with inferior OS.This study showed that compared to treatment with TKI alone, the addition of RT for BrM is associated with an improved OS in patients with EGFRm NSCLC. These results are complementary to the growing body of retrospective data suggesting an inferior survival associated with TKI alone compared to RT with TKI for treatment of BrM in patients with EGFRm NSCLC. Prospective studies are required to further guide the best approach to managing this patient population.T. Kong: None. A. Nichol: None. C. Ho: None. A. Benny: None. N. Chooback: None. I.M. Fraser: None. L. Gondara: None. S. Lefresne: None.

Racial Disparities in the Use of Palliative Radiotherapy for Black Patients With Multiple Myeloma in the United States

<h3>Purpose/Objective(s)</h3> Multiple myeloma (MM) is a hematologic malignancy that disproportionately affects African Americans (AA) and has a natural history that is often characterized by painful osseous lesions that are amenable to palliative radiotherapy (RT). There are known racial disparities in the definitive treatment of MM and pain management in general in the AA community compared to other racial groups. We sought to determine if racial disparities also exist in use of palliative RT for MM in the United States. <h3>Materials/Methods</h3> The National Cancer Database was queried for patients 18 years and older who were diagnosed with MM from 2004-2016 and received radiation. RT dose was limited to between (and including) 4Gy to 30Gy to exclude non-standard doses, incomplete courses, and patients treated for plasmacytoma. The main independent variable under investigation was race/ethnicity, defined as non-Hispanic white (NHW), non-Hispanic black (AA), Hispanic, and other race. Outcomes of interest included receipt of palliative RT within 12 months of MM diagnosis and death within 30 days of initiation of palliative RT. Additional covariates included socioeconomic factors, underlying health, and treatment factors. Multivariable logistic regression analyses were performed to measure the associations of patient race/ethnicity with the odds receiving radiation within 12 months of diagnosis and odds of death within 30 days of receiving the first course of RT. <h3>Results</h3> Of 23,728 NCDB multiple myeloma patients receiving palliative RT within 12 months of diagnosis, 15.5% of NHW patients, 14.3% of AA patients, 15.8% of Hispanic patients, and 14.4% of other racial/ethnic group patients received palliative RT. The odds of receiving RT were 13% less for AAs compared to NHWs (OR = 0.87, CI = 0.83-0.90, <i>P</i> < 0.0001). Of those receiving radiation, the odds of dying within 30 days of RT were 18% less for AAs compared to NHWs (OR = 0.82, 95% CI = 0.67-1.00, <i>P</i> = 0.046). <h3>Conclusion</h3> This study of the NCDB demonstrates that in addition to previously documented disparities in definitive management of MM, AA patients are also less likely to receive palliative RT within 12 months of diagnosis and at the end of life.

COVID-19 Testing Trends: Pre-Radiation and Throughout Cancer Care

Purpose/Objective(s)Timely care is critical for individuals diagnosed with cancer—despite the ongoing COVID-19 pandemic—as delays adversely affect cancer outcomes. Patients presenting for radiotherapy (RT) at a single institution who underwent COVID-19 screening procedures prior to RT were analyzed regarding treatment delays and disparities.Materials/MethodsOur institution is an urban multidisciplinary cancer center. In April 2020, our Radiation Oncology department implemented universal COVID-19 screening protocols prior to RT initiation (with possible patient opt-out) to ensure patient/staff safety. Patients did not start RT until testing negative. We collected patient demographics and COVID-19 testing information on patients planned for RT from April to October 2020. We studied trends of other lifetime COVID-19 testing that these patients received to evaluate for overall delays. Summary statistics were analyzed within a data collection web application.Results177 consecutive patients with cancer were scheduled to begin RT. 15 (8.5%) declined pre-RT COVID-19 testing and proceeded to RT. Of patients who consented to pre-RT testing, 99 (61.1%) were female; mean age was 60.6 (range 24-94). Most patients were Black (n = 98, 60.5%). 61 (37.7%) and 41 (25.3%) were insured through Medicare and Medicaid, respectively. Common primary cancer sites were breast (n = 52, 32.1%), prostate (n = 27, 16.7%), and lung (n = 23, 14.2%). 58 (35.8%) patients presented with metastatic disease; the most common metastatic sites were bone (n = 26, 44.8%) and brain (n = 12, 20.7%). Most patients received external RT (n = 152, 93.8%), primarily adjuvant (n = 66, 40.7%) and palliative (n = 59, 36.4%) RT. One (0.6%) asymptomatic patient tested "presumptive positive" for COVID-19 pre-RT. The patient was COVID-19 negative on immediate repeat testing and proceeded to RT. Overall, the 162 patients who consented to pre-RT testing received 549 total lifetime COVID-19 tests. Most of these patients received palliative RT (n = 219, 39.9%), followed by adjuvant (n = 199, 36.2%) and definitive RT (n = 101, 18.4%). Mean number of total COVID-19 tests per patient was 3.4 (range 1-14). Only 32 patients (19.8%) were administered a solitary pre-RT COVID-19 screening test. 24 (14.8%) patients had at least one positive COVID-19 test over the study period. In total, 32 (5.8%) positive COVID-19 test results were documented; 11 patients (6.8%) experienced a mean RT delay of 4.0 (range 3-8) weeks until testing negative. Other care delays included surgical/diagnostic procedure delays (n = 4), delayed presentation due to COVID-19 fears (n = 2), and travel restrictions (n = 1).ConclusionThe majority of patients with cancer planned for RT tested negative for COVID-19 and proceeded to RT without delay. However, delays prior to radiation oncology consultation due to diagnostic workup, imaging, or biopsies, as well as testing positive for COVID-19, could intensify underlying disparities affecting our urban patient population.

Role of Pelvic Radiation in Management of Non-Metastatic Pathological Node-Positive Prostate Cancer: A Single Institution Experience

Pathological T2-4 N1 M0 prostate cancer (Pca) has a heterogeneous natural history. So far, only one randomized control trial has established the current standard of care of immediate androgen deprivation (ADT) after prostatectomy and lymph node dissection. The role of pelvic radiation (RT) for this cohort of patients remains unknown. The purpose of this study is to perform a retrospective review of our institutional experience to provide much-needed information that may improve the outcome of these very high-risk patients.We identified patients with pT2-4 N1 M0 disease treated in our institution from 2006 to 2016. We reviewed ADT and RT records in addition to patient and disease characteristics. Kaplan-Meier analyses were utilized to evaluate overall survival (OS) and progression-free survival (PFS, defined as either biochemical or clinical evidence of disease recurrence).We identified a total of 94 patients with pT2-4N1M0 Pca with patient demographic and disease characteristics shown in the table. A total of 72 patients had postoperative RT with a median follow-up of 85.9 months (range 15 to 175 months). Among patients receiving RT, 54/72 (75%) received ADT concurrently (median duration of 24 months, range 4 -36 months). The median time from prostatectomy to RT initiation was 6 months (range 3-90 months). RT of 7 patients was initiated after PSA progression. For patients without RT, 15/22 (68%) received ADT (median duration of 24 months, range 3 to 96 months); the median follow-up was 91 months (range 9 to 164 months). The estimated 5-year OS for patients with RT and without RT were 100% and 85.7%, respectively (P = 0.04). The estimated 5-year PFS for patients with RT and without RT were 80.9% and 62.8%, respectively (P = 0.19). Among patients who received ADT, the estimated 5-year PFS was 82.3% with RT and 63.8% without RT, respectively (P = 0.26).For a select group of patients with pT2-4N1M0 Pca, postoperative pelvic RT in combination with ADT appeared to have prolonged OS. Further investigation to stratify this group of patients, and ultimately prospective clinical trials to establish the effectiveness of combined pelvic RT and systemic treatment is needed for this cohort of high-risk patients.

Deterioration of pancreatic exocrine function in carbon ion radiotherapy for pancreatic cancer

Background and purposeIn radiotherapy (RT) for pancreatic cancer, the pancreas is considered an important organ at risk. However, there are insufficient reports on pancreatic function deterioration after X-ray RT as organ at risk, and there are no reports on those after carbon ion (C-ion) RT. Here, we evaluated pancreatic exocrine insufficiency (PEI) after C-ion RT using dose-volume histogram (DVH) analysis. Materials and methodsData were retrospectively collected from patients who had undergone C-ion RT for pancreatic cancer between July 2013 and June 2019. The prescribed C-ion doses were 55.2 Gy (relative biological effectiveness) in 12 fractions. Serum pancreatic amylase and lipase values were measured before and after C-ion RT. In DVH analysis, we assessed V5Gy–50Gy and V<5Gy–50Gy of pancreatic volume and analyzed whether these DVH parameters involved PEI. ResultsThirty-three patients were included in the analysis. The median follow-up duration after the initiation of C-ion RT in these patients was 15.8 months (range, 4.3–64.8). During and after treatment, 57.6% of patients developed PEI within 13.6 months, defined as pancreatic amylase and lipase deficiencies. In DVH analysis, V<5Gy was the most effective factor for the PEI, and the cutoff value for developing PEI in V<5Gy was 4.57 cm3. ConclusionWe showed that pancreatic exocrine function declined after C-ion RT for pancreatic cancer and that PEI was initiated early in the course of C-ion RT. Additionally, a low dose of DVH parameters, such as V<5Gy, was a prognostic factor of PEI.

Influence of Timing Between Androgen Deprivation Therapy and External Beam Radiation Therapy in Patients With Localized, High-Risk Prostate Cancer

PurposeTreatment with long-term androgen deprivation therapy (ADT) and radiation therapy (RT) is the nonsurgical standard-of-care for patients with high- or very high-risk prostate cancer (HR-PC), but the optimal timing between ADT and RT initiation is unknown. We evaluate the influence of timing between ADT and RT on outcomes in patients with HR-PC using a large national cancer database. Methods and MaterialsData for patients with clinical T1-T4 N0, M0, National Cancer Comprehensive Network HR-PC who were treated with definitive external RT (≥60 Gy) and ADT starting either before or within 14 days after RT start were extracted from the National Cancer Database (2004-2015). Patients were grouped on the basis of ADT initiation: (1) >11 weeks before RT, (2) 8 to 11weeks before RT, and (3) <8 weeks before RT. Kaplan-Meier, propensity score matching, and multivariable Cox proportional hazards were performed to evaluate overall survival (OS). ResultsWith a median follow-up of 68.9 months, 37,606 patients with HR-PC were eligible for analysis: 13,346 (35.5%) with >11 weeks of neoadjuvant ADT, 11,456 (30.5%) with 8 to 11 weeks of neoadjuvant ADT; and 12,804 (34%) patients with <8 weeks of neoadjuvant ADT. The unadjusted 10-year OS rates for >11 weeks, 8 to 11 weeks, and <8 weeks neoadjuvant ADT groups were 49.9%, 51.2%, and 46.9%, respectively (P = .002). On multivariable and inverse probability of treatment weighting analyses, there was a significant OS advantage for patients in the 8 to 11 weeks neoadjuvant ADT group (adjusted hazard ratio 0.90; 95% confidence interval, 0.86-0.95; P < .001) but not the >11 weeks group. ConclusionsNeoadjuvant ADT initiation 8 to 11 weeks before RT is associated with significantly improved OS compared with shorter neoadjuvant ADT duration. Although prospective validation is warranted, this analysis is the largest retrospective study suggesting an influence of timing between ADT and RT initiation in HR-PC.

Cancer stem cells in hepatocellular carcinoma - from origin to clinical implications.

Hepatocellular carcinoma (HCC) is an aggressive disease with a poor clinical outcome. The cancer stem cell (CSC) model states that tumour growth is powered by a subset of tumour stem cells within cancers. This model explains several clinical observations in HCC (as well as in other cancers), including the almost inevitable recurrence of tumours after initial successful chemotherapy and/or radiotherapy, as well as the phenomena of tumour dormancy and treatment resistance. The past two decades have seen a marked increase in research on the identification and characterization of liver CSCs, which has encouraged the design of novel diagnostic and treatment strategies for HCC. These studies revealed novel aspects of liver CSCs, including their heterogeneity and unique immunobiology, which are suggestive of opportunities for new research directions and potential therapies. In this Review, we summarize the present knowledge of liver CSC markers and the regulators of stemness in HCC. We also comprehensively describe developments in the liver CSC field with emphasis on experiments utilizing single-cell transcriptomics to understand liver CSC heterogeneity, lineage-tracing and cell-ablation studies of liver CSCs, and the influence of the CSC niche and tumour microenvironment on liver cancer stemness, including interactions between CSCs and the immune system. We also discuss the potential application of liver CSC-based therapies for treatment of HCC.

Delayed initiation of radiation therapy is associated with inferior outcomes for breast cancer patients with hormone receptor-negative tumors after breast-conserving surgery.

To investigate whether the interval between adjuvant chemotherapy (CT) completion and postoperative radiation therapy initiation (ICR) after breast-conserving surgery (BCS) affects ipsilateral breast tumor recurrence (IBTR) or survival. All women who were diagnosed with invasive breast cancer and underwent BCS between 2005 and 2014 were included. In total, 1,472 patients underwent adjuvant CT followed by postoperative radiation therapy (RT) (CT+), whereas 402 patients received postoperative RT alone (CT-). Analyses were stratified by ICR and the interval between surgery and the initiation of postoperative RT (ISR) in these two cohorts. The cutoff points for treatment delay were 47 days in the CT+ cohort and 69 days in the CT- cohort. IBTR, local-regional failure (LRF), disease-free survival (DFS), and overall survival (OS) were assessed through Kaplan-Meier (K-M) analysis. Univariate and multivariate regression analyses were performed to determine the prognostic factors of survival outcomes. The median follow-up duration was 56 months. There was an association between a delay in ICR and an increase in IBTR in the CT+ group (P=0.014 for intervals ≤47 vs. >47 days). This association was confirmed by multivariate analyses [hazard ratio (HR) of 2.766; P=0.046] in the hormone receptor-negative subgroup. The 5-year cumulative incidence rates of IBTR were 1.3% and 3.3% (≤47 vs. >47 days, respectively) in the CT+ cohort. For patients in the CT- cohort, a longer delay of initiation of postoperative RT (≤69 vs. >69 days) significantly decreased DFS (HR of 6.430; P=0.002). The 5-year cumulative incidence rates of disease recurrence were 3.0% for RT starting ≤69 days after surgery and 12.6% for RT starting >69 days after surgery. A high IBTR rate was related to an ICR beyond 47 days. Delay of RT after CT or surgery among patients who undergo BCS should be avoided, especially among patients in the hormone receptor-negative subgroup.

Stereotactic radiosurgery for treatment of radiation-induced meningiomas: a multiinstitutional study.

Radiation-induced meningiomas (RIMs) are associated with aggressive clinical behavior. Stereotactic radiosurgery (SRS) is sometimes considered for selected RIMs. The authors investigated the effectiveness and safety of SRS for the management of RIMs. From 12 institutions participating in the International Radiosurgery Research Foundation, the authors pooled patients who had prior cranial irradiation and were subsequently clinically diagnosed with WHO grade I meningiomas that were managed with SRS. Fifty-two patients underwent 60 SRS procedures for histologically confirmed or radiologically suspected WHO grade I RIMs. The median ages at initial cranial radiation therapy and SRS for RIM were 5.5 years and 39 years, respectively. The most common reasons for cranial radiation therapy were leukemia (21%) and medulloblastoma (17%). There were 39 multiple RIMs (35%), the mean target volume was 8.61 ± 7.80 cm3, and the median prescription dose was 14 Gy. The median imaging follow-up duration was 48 months (range 4-195 months). RIM progressed in 9 patients (17%) at a median duration of 30 months (range 3-45 months) after SRS. Progression-free survival at 5 years post-SRS was 83%. Treatment volume ≥ 5 cm3 predicted progression (HR 8.226, 95% CI 1.028-65.857, p = 0.047). Seven patients (14%) developed new neurological symptoms or experienced SRS-related complications or T2 signal change from 1 to 72 months after SRS. SRS is associated with durable local control of RIMs in the majority of patients and has an acceptable safety profile. SRS can be considered for patients and tumors that are deemed suboptimal, poor surgical candidates, and those whose tumor again progresses after removal.

PD57-02 NATIONAL CANCER DATABASE ANALYSIS ASSESSING THE IMPACT OF TREATMENT MODALITIES ON SURVIVAL OUTCOMES IN LOCALIZED NEUROENDOCRINE PROSTATE ADENOCARCINOMA

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy IV (PD57)1 Sep 2021PD57-02 NATIONAL CANCER DATABASE ANALYSIS ASSESSING THE IMPACT OF TREATMENT MODALITIES ON SURVIVAL OUTCOMES IN LOCALIZED NEUROENDOCRINE PROSTATE ADENOCARCINOMA Chandler Bronkema, Sohrab Arora, Jacob Keeley, Nikola Rakic, Akshay Sood, Deepansh Dalela, Maxwell Stricker, Phil Olson, Craig G. Rogers, Mani Menon, and Firas Abdollah Chandler BronkemaChandler Bronkema More articles by this author , Sohrab AroraSohrab Arora More articles by this author , Jacob KeeleyJacob Keeley More articles by this author , Nikola RakicNikola Rakic More articles by this author , Akshay SoodAkshay Sood More articles by this author , Deepansh DalelaDeepansh Dalela More articles by this author , Maxwell StrickerMaxwell Stricker More articles by this author , Phil OlsonPhil Olson More articles by this author , Craig G. RogersCraig G. Rogers More articles by this author , Mani MenonMani Menon More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002091.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Neuroendocrine (NEC) adenocarcinoma is considered a rare histological variant of prostate adenocarcinoma (PCa). Given the rarity of this malignancy, optimal treatment strategies for men with nonmetastatic NEC PCa is largely unknown. We sought to describe the impact of initial surgery, radiotherapy (RT), systemic therapy (ST) and observation on overall survival (OS) in men with nonmetastatic NEC PCa. METHODS: We selected 456 cases of localized NEC PCa, diagnosed between 2004 and 2015, within the National Cancer Database. Covariates included age, race, Charlson comorbidity score, clinical T stage, clinical lymph node stage, serum prostate specific antigen (PSA), and income. Cox regression analysis tested the impact of treatment (surgery, RT, ST and observation) on OS after adjusting for all covariates. Adjusted Kaplan-Meier estimates were used to visualize the impact of treatment modality on OS. RESULTS: In men with nonmetastatic NEC PCa, median (IQR) age and PSA were 70 (63-78) years and 5.3 (2.1-11.1) ng/mL, respectively. Advanced local stage (≥cT3a) was most frequently observed in patients treated with ST (52.6%), followed by those treated with RT (40.2%), observation (20.0%) and surgery (15.9%, p<0.001). Serum PSA at presentation was highest in the ST cohort (median 15.6 ng/ml, IQR: 1.6-49.1), followed by the surgery (median 5.9 ng/ml, IQR: 4.0-9.6) and observation cohorts (median 5.9 ng/ml, IQR: 1.6-11.3), and finally, the RT cohort (median 4.6 ng/ml, IQR: 1.9-11.3, p=0.002). Estimated 5-year OS was highest in the surgery cohort (58.1%), followed by the RT (33.8%), observation (13.6%) and ST cohorts (7.9%; all p<0.001). Adjusted Kaplan-Meier estimates are displayed in the figure below. Multivariable analysis showed that compared to men treated surgically, OS was significantly lower for patients under observation (HR 5.2; 95% CI: 2.5-10.6); however, OS was not significantly different for patients receiving RT (HR 1.0; 95% CI: 0.6-1.6) or ST (HR 1.7; 95% CI: 0.9-3.2). CONCLUSIONS: In men diagnosed with localized neuroendocrine PCa, initial surgical treatment is associated with more favorable OS outcomes compared to observation but not RT or ST. Our findings should be interpreted within the framework of a retrospective study design. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1009-e1010 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Chandler Bronkema More articles by this author Sohrab Arora More articles by this author Jacob Keeley More articles by this author Nikola Rakic More articles by this author Akshay Sood More articles by this author Deepansh Dalela More articles by this author Maxwell Stricker More articles by this author Phil Olson More articles by this author Craig G. Rogers More articles by this author Mani Menon More articles by this author Firas Abdollah More articles by this author Expand All Advertisement Loading ...

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.

Effects of palliative radiotherapy and bisphosphonate usage on bone turnover marker levels in cancer patients with osteolytic bone metastases.

Objectives In this study, we aimed to investigate the bone turnover marker levels according to bisphosphonate usage and radiotherapy (RT) in cancer patients with metastases in osteolytic pattern.Patients and methods A total of 52 patients (13 males, 39 females; median age: 52 years; range, 37 to 78 years) treated with RT for osteolytic bone metastases between April 2005 and April 2006 were retrospectively analyzed. Bone-specific alkaline phosphatase (BAP), amino-terminal cross-linked telopeptide of type I collagen (NTX-I), amino-terminal propeptide of type I procollagen (PINP), osteocalcin (OC), deoxypyridinoline (DPD), pyridinoline (PYD), alkaline phosphatase (ALP), creatinine, calcium (Ca), phosphate (P), magnesium (Mg), and 24-h urine Ca levels were measured in blood and urine before the initiation of RT, six weeks and six months after RT.Results A decrease in BAP, PINP, and creatinine levels was observed after RT (Week 6 p=0.006, Month 6 p=0.008). Sixteen patients who already used bisphosphonate before RT were excluded from statistical calculation. The remaining 36 patients who were treated with bisphosphonate after the first blood test were evaluated separately. In this group of patients, BAP, PINP, NTX, creatinine, and Ca levels significantly increased at six weeks after RT. The PINP and creatinine values significantly decreased at six months after RT. The variation between two different RT arms was assessed with repeated measures variance analysis. There was a statistically significant difference for NTX, OC, and creatinine levels between the first and second measurements.Conclusion Radiotherapy is an effective method in the treatment of osteolytic bone metastases. Bone turnover markers can provide an objective evaluation on RT response and parallel to imaging modalities criteria for evaluation. Bisphosphonates may alter the levels of these indicators. However, in this study, there were no statistically significant differences between the levels of markers for two different RT schedules.

THER-02. PARP Inhibitor Tolerability and Impact on Progression-Free Survival in Patients with High-Grade, Ovarian Carcinoma with Brain Metastasis: A Case-Series

Abstract Brain metastases secondary to ovarian carcinoma is an uncommon but increasing phenomenon. PARP inhibitors (PARPi) are increasingly used as an adjunctive treatment in patients with central nervous system metastases (CNS). Historically brain metastases has a historically poor prognosis. Five women with a mean age of 60.4 ± 7.6 years were included. All had stage IIIC/IV ovarian cancer and diagnosed with brain metastases at recurrence. Three underwent resection for oligometastatic disease followed by post-operative stereotactic radiosurgery (SRS), one had SRS without surgery, and one patient underwent whole brain radiotherapy for multiple metastases. Pathology was confirmed in those who were resected. Two patients had evidence of systemic disease in addition to CNS spread. Three women were BRCA1/2 Positive. Following initial radiotherapy, one patient received adjuvant chemotherapy followed by olaparib maintenance, one received 13 cycles of bevacizumab/olaparib, followed by olaparib maintenance. A third patient was treated with olaparib/bevacizumab and two patients received olaparib monotherapy, both of whom continued on therapy. All received olaparib therapy during their treatment and all had minor dose modifications due to side effects. Mean survival from initial cancer diagnosis was 62.4 ± 20.4 months. Mean duration of PARPi therapy was 27.6 ± 16.8 months. Mean survival following CNS recurrence was 22.8 ± 12 months. One patient is disease-free, two patients are alive with stable disease, one patient is alive but off treatment secondary to progression, and one patient is deceased secondary to progression of her brain metastases after being on PARP therapy for 18 months. The cohort remained highly functional across the trajectory of their disease with ECOG scores of 1 (n=4) or 0 (n=1). The results of this single institution retrospective evaluation suggest olaparib in combination with radiotherapy +/- bevacizumab is well tolerated and can provide additional benefit in patients with brain metastases secondary to ovarian carcinoma.

Predictors for Fear of Cancer Recurrence in Breast Cancer Patients Referred to Radiation Therapy During the COVID-19 Pandemic: A Multi-Center Cross-Section Survey.

ObjectiveThe outbreak of COVID-19 pandemic has greatly impacted on radiotherapy (RT) strategy for breast cancer patients, which might lead to increased distressing psychological symptoms. We performed a multi-center cross-section survey to investigate prevalence of fear of cancer recurrence (FCR) and predictors for FCR in patients referred to RT during pandemic.Methods542 patients were consecutively enrolled from three regions in China including Yangtze Delta River Region, Guangdong and Shanxi province. Patients’ characteristics were collected using an information sheet, Fear of progression questionnaire-short form, Hospital Anxiety/Depression Scale and EORTC QLQ-C30. The hierarchical multiple regression models were performed.Results488 patients with complete data were eligible. The RT strategy was affected in 265 (54.3%) patients, including 143 with delayed RT initiation, 66 believing to have delayed RT initiation but actually not, 24 with RT interruptions, 19 shifting to local hospitals for RT and the remaining 13 influenced on both RT schedule and hospital level. The model explained 59.7% of observed variances in FCR (p<0.001) and showed that influence of RT strategy had significantly impacted on FCR (△R2 = 0.01, △F=2.966, p=0.019). Hospitals in Shanxi province (β=-0.117, p=0.001), emotional function (β=-0.19, p<0.001), social function (β=-0.111, p=0.006), anxiety (β=0.434, p<0.001) and RT interruption (β=0.071, p=0.035) were independent predictors.ConclusionsRT strategy for breast cancer patients was greatly influenced during pandemic. RT interruption is an independent predictor for high FCR. Our findings emphasize the necessity to ensure continuum of RT, and efforts should be taken to alleviate FCR through psychological interventions.