Conventional Palliative Radiotherapy Research Articles

Palliative radiotherapy for painful non-bone lesions in patients with advanced cancer: a single center retrospective study.

This retrospective study aimed to assess the efficacy and safety of palliative radiotherapy for painful non-bone lesions in patients with advanced cancer. We enrolled patients with painful non-bone lesions who underwent conventional palliative radiotherapy between September 2018 and September 2022. The treatment targets included primary tumor lesions, lymph node metastases, non-bone hematogenous metastases, and other lesions. The primary endpoint was the overall pain response rate in evaluable patients, determined based on the International Consensus Pain Response Endpoint criteria. The secondary endpoints included overall survival, pain recurrence, and adverse events. Of the 420 screened patients, 142 received palliative radiotherapy for painful non-bone lesions, and 112 were evaluable. A pain response was achieved in 67 patients (60%) of the 112 evaluable patients within a median of 1.2months. Among these patients, 25 exhibited complete response, 42 partial response, 18 indeterminate response, and 27 pain progression. The median survival time was 5.5months, recorded at a median follow-up of 6.0months, during which 67 patients died. Multivariate analysis identified poor performance status scores of 2-4, opioid use, and re-irradiation as independent factors associated with a reduced likelihood of achieving a pain response. Pain recurrence occurred in 18 patients over a median of 4.1months. Seventeen patients had grade 1-2 adverse events, while none experienced grade 3 or higher toxicity. Palliative radiotherapy can potentially be a safe and well-tolerated modality for managing painful non-bone lesions, with a low rate of adverse events.

Examining the Efficacy and Safety Profile of Palliative Radiotherapy Using 30 Gy in 5 Fractions

Higher biological equivalent doses of radiotherapy (RT) can improve symptom palliation and local control in select tumor sites. However, not all patients meet criteria for treatment with stereotactic ablative radiotherapy (SABR). Furthermore, SABR is a resource intensive technique which may limit its use in many centers. The 30 Gray in 5 fractions regimen (30/5) stems from a modification of 5-fraction SABR regimens. It is a conformal, homogenous hypo-fractionated regimen that delivers higher dose than conventional palliative RT while still respecting the normal tissue constraints for 5-fraction SABR. It uses streamlined contouring and planning with less stringent requirements for immobilization and image guidance, compared to what is required for SABR. This study evaluates the clinical outcomes of patients receiving 30/5. A single institution retrospective review of clinical and treatment data was performed for patients who received 30/5 from October 2020 to August 2022. Local control (LC) was calculated for all treatment courses. Distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were calculated for all patients. Survival analyses were analyzed by the Kaplan-Meier method and curves compared by log-rank test. Univariate and multivariate analyses were performed using cox-regression analysis. A total of 77 patients and 92 courses of 30/5 were available for analysis. The most common primary tumor was lung (44%), followed by gastrointestinal (GI; 20%), breast (10%), and genitourinary (10%). The median age of patients was 64 years (range: 37-93). The median tumor size treated was 11.4 cm^3 (range: 0.3 - 210.9 cm^3). Treatment sites included lung (31%), lymph nodes (22%), non-spine bone (20%), and spine (15%). At median follow-up of 10.1 months (mo), 25 deaths occurred. Median LC after receiving 30/5 was 18.5 mo (95% CI: 15.7-21.3 mo), median DMFS was 6.6 months (95% CI: 4.6-8.6 mo), median PFS was 6.4 mo (95% CI: 4.9-8.0 mo), and median OS was 18.1 mo (95% CI: 13.1-23.1 mo). Median time to initiating, restarting, or changing systemic therapy was 12.8 mo (95% CI: 7.6-18.0 mo). Radiosensitive (lung, prostate, breast, gynecological, and head/neck) tumors had better LC than radioresistant (GI, renal cell, sarcoma, melanoma) tumors (median 20.9 vs 12.1 mo, p < 0.02). Six grade 2 toxicities occurred (6.5% of all treatments). No grade 3 or higher toxicities occurred. The 30/5 regimen is a safe, well-tolerated, and resource efficient regimen with effective local control. This may serve as a practical alternative for patients who require palliative RT but not optimal candidates for SABR. As expected, radiosensitive tumors had better local control than radioresistant tumors. Future research can further explore the safety, efficacy, and indications of 30/5 as a palliative RT option.

Long Term Outcomes of Conventional Palliative Radiotherapy in Bone Metastases of Lung Cancer: A Prospective Study

Bone metastases (BM) are highly prevalent in metastatic lung cancer (LC) leading to consequential morbidity and a decline in quality of life. The identification of oncogenes mutation and introduction of targeted therapy has prolonged the survival and therefore evaluation of long-term pain response rates, durability and re-irradiation (Re-RT) with conventional radiotherapy (RT) is crucial, especially in LMIC where penetration of stereotactic body radiotherapy for BM is poor. This prospective observational study included consecutive patients with histologically proven LC with radiologically confirmed BM. The primary objective was to evaluate the pain response rates in lung cancer patients with bone metastases treated with palliative RT. Palliative RT to BM was delivered using a conventional/conformal technique. The International Bone Metastases Consensus response criteria using Numeric Pain Rating Scale (NPRS) and Oral Morphine Equivalent Dose (OMED) was used to evaluate the pain response at 12, 24, and 52 weeks. Assuming the worst-case scenario, pain progression-free survival (PPFS) was calculated from the date of baseline assessment to the date of pain progression (PP) or death using Kaplan-Meier survival analysis. Known prognostic factors were evaluated using Cox regression analysis. From June 2020 to August 2022, 250 patients of NSCLC (94%) were accrued. The majority were male (66%), smokers (35%), lytic lesions (75%) and in the axial skeleton (82%). The oncogenic mutation was seen in 123 (49%) patients. At baseline, the mean OMED was 20mg/day (SD-21), and the mean pain score was 6 (SD-2.3). The majority (66%) received an 8 Gy single fraction with only 3% treated with SBRT. In evaluable patients, the CR and PR rates at 12 (n-161) and 24 weeks (n-121) were 34%, 40%, and 44%, 35% respectively. The indeterminate response rate (IRR) at 3 and 6 months were 18% while the rate of PP was 6%. On multivariate analysis, negative oncogene mutation {HR-0.34 (CI 0.22- 0.50), p<0.0001} and soft tissue mass {HR-0.46 (CI 0.31- 0.68) p<0.0001} were significant prognostic factors for pain progression. Of 71 evaluable patients at 1 year, 56% had a complete response with an ORR of 87%. In patients with oncogene mutation, the CR rates at 12 (n-101), 24 (n-77), and 52 weeks were 40%, 47%, and 60% with an ORR of 86%. PP is observed in less than 4%. Pain response was significantly more durable than mutation negative (8 vs 3 months, p-0.003). Re-RT rate was overall 11% (n = 27) and 8.2% in oncogene mutation patients. Re-RT rate with single-fraction was 8% and 3% with fractionated RT. The median time to Re-RT was 9.7 weeks. The PPFS was 70% and 60% at 12 and 24 weeks, respectively. This prospective study in an LC-specific population demonstrated excellent CR and PR rates with conventional RT. Durable pain relief with modest Re-RT rates with single fraction, particularly in oncogene mutation compels us to evaluate the role of SBRT for BM, especially in LMIC in a randomized setting.

139 - Comparison of VMAT (volumetric modulated arc therapy) delivery of high-dose palliative radiotherapy (RT) to lung via Eclipse Planning System (EPS), to conventional palliative radiotherapy delivery via ADW planning system

139 - Comparison of VMAT (volumetric modulated arc therapy) delivery of high-dose palliative radiotherapy (RT) to lung via Eclipse Planning System (EPS), to conventional palliative radiotherapy delivery via ADW planning system

Real-world Practice Patterns and Safety of Concurrent Radiotherapy and Cabozantinib in Metastatic Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

BackgroundThere is a paucity of data on the safety of cabozantinib use in combination with radiotherapy. ObjectiveTo report the practice patterns, safety, and efficacy of cabozantinib with radiotherapy in metastatic renal cell carcinoma (mRCC). Design, setting, and participantsAn international multicenter retrospective study was conducted. Patients with mRCC treated with cabozantinib at any line of therapy and who received radiotherapy between 30 d prior to the start date of cabozantinib and 30 d following discontinuation of cabozantinib, from 2014 to 2020, were included. Concurrent use was defined as the use of cabozantinib on radiotherapy treatment days during any course of radiotherapy. Outcome measurements and statistical analysisThe primary outcomes of interest were the rate of grade ≥3 adverse events (AEs) occurring within 90 d of receipt of radiotherapy. Secondary outcomes included hospitalization rate and patterns of cabozantinib and radiotherapy use. Baseline characteristics and AEs were presented descriptively. Results and limitationsA total of 127 consecutive patients were included. Most patients had clear cell histology (88%), had International Metastatic Renal Cell Carcinoma Database Consortium intermediate-risk disease (57%), and had received at least one prior line of therapy (93%). Of 127 patients, 67 (53%) received concurrent cabozantinib with radiotherapy, while the remaining held cabozantinib on radiotherapy days. Overall, grade 3–4 AEs occurred in 6.3% (n = 8/127) of patients. No grade 5 events were observed. In patients treated with conventional palliative radiotherapy (n = 88), the rate of grade 3–4 AEs in those who had concurrent versus those who had nonconcurrent cabozantinib was 6.3% (n = 3/48) versus 5.0% (n = 2/40). No patient was hospitalized due to radiotherapy-related toxicity. In patients treated with stereotactic ablative body radiotherapy (SABR; n = 50), the rate of grade 3–4 AEs in those who had concurrent versus those who had nonconcurrent cabozantinib was 3.6% (n = 1/28) versus 9.1% (n = 2/22). One patient in the nonconcurrent group was hospitalized due to muscle weakness suspected to be related to associated vasogenic edema 19 d after SABR for multiple brain metastases. ConclusionsIn this real-world study of patients with mRCC treated with cabozantinib, 53% of patients received radiotherapy concurrently, with few grade 3–4 AEs reported within 90 d of receiving radiotherapy. The use of radiotherapy and cabozantinib requires a risk-benefit assessment of patient and disease characteristics to optimize therapy regimens. Patient summaryOur study reports the real-world experience of using radiotherapy in patients receiving cabozantinib for metastatic kidney cancer. Over half of the patients continued taking cabozantinib while receiving radiotherapy, and few patients developed serious side effects. The combined use of radiotherapy and cabozantinib requires a careful risk-benefit assessment to achieve optimal treatment outcomes.

Association Between EGFR and ALK Mutation Status on Patient-Reported Symptoms After Palliative Radiation for Bone Pain in NSCLC

IntroductionAfter palliative radiotherapy for bone metastases from NSCLC, up to 30% of patients may derive no symptomatic benefit, and there are a lack of biological predictors for this. The purpose was to investigate whether EGFR and ALK genetic rearrangements were associated with greater rates of pain response to palliative radiotherapy. MethodsPatients were identified from a prospectively collected patient-reported outcomes database for all patients with lung cancer treated with conventional palliative radiotherapy for bone metastases from 2013 to 2016 in the province of British Columbia. Patients were divided on the basis of mutational status into the following: EGFR and ALK wild type (WT), EGFR mutation present (EGFR+), or ALK mutation present (ALK+). Patient-reported outcomes of global pain severity were collected before and after radiotherapy and on an ordinal scale of 0 to 4, with 0 representing no bone pain and 4 representing the maximal possible bone pain. The primary outcome was the rate of partial pain response (any improvement in score), and the secondary outcome was the rate of complete pain response (final pain score of 0). Stepwise, multivariable logistic analysis was used to compare response rates between treatment courses for different mutational statuses. ResultsThe final cohort consisted of 388 treatment courses for 329 unique patients. For the WT, EGFR+, and ALK+ groups, there were 180, 63, and nine treatment courses, respectively. There were 92 patients with no ALK and EGFR testing. The most common treatment fractionations were 8 Gy in one fraction (188 of 388) and 20 Gy in five fractions (160 of 388), and use of multifraction radiotherapy did not differ between mutation status groups (p = 0.3). Partial pain response rates were as follows: WT 63%, EGFR+ 75%, and ALK+ 78%. On multivariable analysis, rates of partial response were higher for EGFR+ (OR = 5.4, p < 0.001) and for ALK+ (OR = 12.8, p = 0.008) in comparison to WT. Complete response rates were as follows: WT 20.5%, EGFR+ 35%, and ALK+ 67%. On multivariable analysis, complete response was not significantly increased in EGFR+ compared with WT (OR = 1.6, p = 0.127). ALK+ mutation status was associated with a higher rate of complete response compared with WT (OR = 5.2, p = 0.031). ConclusionsThere was an association between EGFR+ and ALK+ tumors and increased rates of partial pain response to palliative radiotherapy.

Prognostic Factors Influencing Survival and a Treatment Pattern Analysis of Conventional Palliative Radiotherapy for Patients with Bone Metastases.

Background: Treatment indication for bone metastases is influenced by patient prognosis. Single-fraction radiotherapy (SFRT) was proven equally effective as multiple fractionation regimens (MFRT) but continues to be underused. Objective: Primary objectives: (a) to identify prognostic factors for overall survival and (b) to analyze treatment patterns of palliative radiotherapy (proportion of SFRT indication and predictive factors of radiotherapy regimen) for bone metastases. Methods: 582 patients with bone metastases who underwent conventional radiotherapy between January 1st 2014–31 December 2017 were analyzed. The Cox proportional hazard model was used to identify predictors of overall survival. For the treatment pattern analysis, 677 radiotherapy courses were evaluated. The logistic regression model was used to identify potential predictors of radiotherapy regimen. Results: The 3-year overall survival was 15%. Prognostic factors associated with poor overall survival were multiple bone metastases [hazard ratio (HR = 5.4)], poor performance status (HR = 1.5) and brain metastases (HR = 1.37). SFRT prescription increased from 41% in 2017 to 51% in 2017. Predictors of SFRT prescription were a poor performance status [odds ratio (OR = 0.55)], lung (OR = 0.49) and urologic primaries (OR = 0.33) and the half-body lower site of irradiation (OR = 0.59). Spinal metastases were more likely to receive MFRT (OR = 2.09). Conclusions: Based on the prognostic factors we identified, a selection protocol for patients candidates for palliative radiotherapy to bone metastases could be established, in order to further increase SFRT prescription in our institution.

Stereotactic Body Radiotherapy (SBRT) Versus Conventional Palliative Radiotherapy (CRT) for Patients With Painful Spinal Metastases: A Phase 3, Randomized Controlled Trial

Background: Conventional external beam radiation (CRT) is standard palliative treatment for spinal metastases; however, complete response rates for pain are low. Stereotactic body radiotherapy (SBRT) delivers high dose ablative radiotherapy. We aimed to compare complete response rates (CR) for pain between SBRT and CRT to painful spinal metastases. Methods: We did this multicenter, phase 2/3, randomised controlled trial in 13 hospitals in Canada and 5 in Australia and New Zealand. Patients were eligible if they were aged 18 years and older, a spine MRI confirmed painful (pain measured as ≥2 points using the Brief Pain Inventory) site of spinal metastasis, no more than three consecutive vertebral segments to be included in the treatment volume, an Eastern Cooperative Oncology Group performance status of 0 to 2, and no frank instability or neurologically symptomatic spinal cord or cauda equina compression. Patients were randomized (1:1) to receive either 24Gy in 2 SBRT fractions or 20Gy in 5 CRT fractions using standard techniques. Treatment assignment was performed centrally using a minimization method to achieve balance for the stratification factors of radioresistant (gastrointestinal, sarcoma, melanoma and renal cell cancer metastases) vs. radiosensitive (all other histologies) histologic type, presence or absence of “Mass” on imaging (extra-osseous paraspinal and/or epidural disease extension), and center. Patients, caregivers and investigators were not masked to the treatment allocation. The primary endpoint was the CR rate for pain at 3 months post-radiation. Final analysis populations included the intent-to-treat (ITT) population for all efficacy endpoints, and the as-treated population for safety and quality assurance analyses. The trial is registered with ClinicalTrials.gov (NCT02512965). Findings: Patients were enrolled from January 2016 to September 2019. All 229 patients were included in the ITT analyses including 4 of the 114 patients randomized to SBRT who did not initiate the study intervention, 2 of the 115 in the CRT arm that initiated at least one fraction of radiation treatment but withdrew prior to completion, 22 (19%) patients in the CRT arm and 16 (14%) patients in the SBRT arm who were in-evaluable at the primary endpoint assessment at 3 months, and 39 (34%) patients in the CRT arm and 36 (32%) patients in the SBRT arm who were inevaluable at the 6 month endpoint. The median baseline worst pain score was 5 (range, 2-10) in both arms, and the median follow-up was 6.7 months (range, 0.2-8.9). At 3 months, 16/115 (14%) in the CRT arm vs. 40/114 (36%) in the SBRT arm (p=0.0002) achieved a CR for pain. Significance was retained on multivariable analyses (MVA, p=0.0003) and the risk ratio (RR) was 1.33 (95% C.I., 1.14 – 1.55) favoring SBRT. At 6 months, 18/115 (16%) in the CRT arm vs. 37/114 patients (33%) in the SBRT arm achieved a CR (p=0.004), significance was retained on MVA (p=0.007), and the RR was 1.24 (95% C.I., 1.07 – 1.44) favoring SBRT. The 3 month radiation site specific progression-free-survival rates for CRT vs. SBRT were 86% vs. 92% and, at 6 months, 69% vs. 75%, respectively. Quality-of-life outcomes were comparable with only financial perception at 1 month (p=0.03) favoring SBRT. Grade 2+ adverse events were observed in 12% and 11% in the CRT and SBRT arms, respectively. Interpretation: SBRT is superior to CRT in improving the CR rate for pain in selected patients with spinal metastases. Trial Registration: (NCT02512965). Funding: Canadian Cancer Society (CCS) and the National Health and Medical Research Council (NHMRC). Declaration of Interests: AS declares prior consulting services and/or honorarium for past educational seminars for Varian Medical Systems, Elekta AB, Astra Zeneca, Medtronic Kyphon, and BrainLAB, and research grants from Elekta AB and Varian Medical Systems. SS declares research grants from Varian Medical Systems, Merck-Sharp-Dohme and Bayer Pharmaceuticals and honorarium for past educational seminars and advisory board participation from Astra Zeneca and Reflexion. SDM declares grant support from Novartis/AAA and honorarium from Ipsen. MF declares grants from Elekta AB and honorarium for past educational seminars from Elekta AB and Varian Medical Systems. JG, IT, MK, MGF, ML, PJM, YL, MB, JB, KD, GLM, RKW, SKL, WRP, and ZG have no conflicts of interests to declare. Ethics Approval Statement: Each participating center obtained approval from their local research ethics board, and each patient provided written informed consent. All data were collected, maintained and analyzed by the Canadian Cancer Trials Group (CCTG) in Kingston, Ontario, Canada. The trial was sponsored in Canada by the CCTG and in Australia and New Zealand by the Trans Tasman Radiation Oncology Group (TROG), and independently monitored by the independent CCTG Data Safety Monitoring Board.

CCTG SC.24/TROG 17.06: A Randomized Phase II/III Study Comparing 24Gy in 2 Stereotactic Body Radiotherapy (SBRT) Fractions Versus 20Gy in 5 Conventional Palliative Radiotherapy (CRT) Fractions for Patients with Painful Spinal Metastases

CCTG SC.24/TROG 17.06: A Randomized Phase II/III Study Comparing 24Gy in 2 Stereotactic Body Radiotherapy (SBRT) Fractions Versus 20Gy in 5 Conventional Palliative Radiotherapy (CRT) Fractions for Patients with Painful Spinal Metastases

Mono-institutional phase 2 study of innovative Stereotactic Body RadioTherapy targeting PArtial Tumor HYpoxic (SBRT-PATHY) clonogenic cells in unresectable bulky non-small cell lung cancer: profound non-targeted effects by sparing peri-tumoral immune microenvironment

BackgroundRadiotherapy-induced lymphopenia may be limiting the success of therapy and could also negatively affect the ability of immune system in mediating the bystander (BE) and abscopal effects (AE). A novel SBRT-based PArtial Tumor irradiation of HYpoxic clonogenic cells (SBRT-PATHY) for induction of the tumoricidal BE and AE by sparing the peritumoral immune microenvironment and regional circulating lymphocytes has been developed to enhance the radiotherapy therapeutic ratio of advanced lung cancer. The aim of this retrospective review of prospectively collected mono-institutional phase 2 study was to compare the outcomes between unconventional SBRT-PATHY and standard of care in unresectable stage IIIB/IV bulky NSCLC.Materials and methodsSixty patients considered inoperable or unsuitable for radical radio-chemotherapy were enrolled and treated using the following 3 regimens: SBRT-PATHY (group I, n = 20 patients), recommended standard of care chemotherapy (group II, n = 20 patients), and institutional conventional palliative radiotherapy (group III, n = 20 patients).ResultsMedian follow-up was 13 months. The 1-year overall survival was 75, 60, and 20% in groups 1, 2 and 3, respectively (p = 0.099). The 1-year cancer specific survival was 90, 60, and 20% in groups 1, 2, and 3, respectively (p = 0.049). Bulky tumor control rate was 95% for SBRT-PATHY compared with 20% in the other two groups. BE and AE were seen by SBRT-PATHY in 95 and 45% of patients, respectively. Multi-variate analysis for cancer specific survival was significant for treatment effect with SBRT-PATHY (p < 0.001) independent of age, sex, performance status, histology, stage, treated bulky site and tumor diameter. SBRT-PATHY resulted in lower toxicity (p = 0.026), and improved symptom control (p = 0.018) when compared to other two treatment options.ConclusionSBRT-PATHY improved treatment outcomes in unresectable NSCLC and should be investigated in larger trials.Present study has been retrospectively registered on 8th of August 2019 by the ethic committee for Austrian region „Kärnten “in Klagenfurt (AUT), under study number A 31/19.

Systematic Review of the Role of Stereotactic Radiotherapy for Bone Metastases.

BackgroundStereotactic radiotherapy (SBRT) might improve pain and local control in patients with bone metastases compared to conventional radiotherapy, although an overall estimate of these outcomes is currently unknown.MethodsA systematic review was carried out following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pubmed, Embase, and Cochrane databases were systematically searched to identify studies reporting pain response and local control among patients with bone metastases from solid-organ tumors who underwent SBRT in 1–6 fractions. All studies prior to April 15, 2017, were included. Study quality was assessed by predefined criteria, and pain response and local control rates were extracted.ResultsA total of 2619 studies were screened; 57 were included (reporting outcomes for 3995 patients) of which 38 reported pain response and 45 local control rates. Local control rates were high with pain response rates above those previously reported for conventional radiotherapy. Marked heterogeneity in study populations and delivered treatments were identified such that quantitative synthesis was not appropriate. Reported toxicity was limited. Of the pain response studies, 73.7% used a retrospective cohort design and only 10.5% used the international consensus endpoint definitions of pain response. The median survival within the included studies ranged from 8 to 30.4 months, suggesting a high risk of selection bias in the included observational studies.ConclusionsThis review demonstrates the potential benefit of SBRT over conventional palliative radiotherapy in improving pain due to bone metastases. Given the methodological limitations of the published literature, however, large randomized trials are now urgently required to better quantify this benefit.

Evaluation of predictive factors of vertebral compression fracture after conventional palliative radiotherapy for spinal metastasis from colorectal cancer.

OBJECTIVE Delayed consequences of spinal radiotherapy (RT), including vertebral compression fracture (VCF), are critical complications. However, the predisposing factors that contribute to VCF after conventional RT are unclear. The aim of this study was to assess the incidence of VCF and to determine the predictors of VCF following conventional spinal RT specific to colorectal cancer (CRC). METHODS The authors retrospectively reviewed 237 spinal segments (147 metastatic and 90 nonmetastatic) in 53 patients with CRC who underwent RT with a median total dose of 30 Gy in 10 fractions between January 2007 and December 2014. The primary end point was the development of a VCF following RT, either de novo VCF or the progression of a baseline VCF. VCFs were assessed using the spinal instability neoplastic score (SINS) criteria. RESULTS Among all 237 spinal segments, 22 VCFs (9.3%) were observed following RT, including 13 de novo and 9 progressive fractures, and the median time to VCF was 4 months. All VCFs developed in metastatic spines. Among 147 metastatic spinal segments, 22 fractures were observed, with a 12-month cumulative incidence of VCF of 14.8%. Results of multivariable analysis indicated sex (p = 0.023) and SINS class II/III (p < 0.001) as risk factors related to development of a VCF in metastatic spinal segments. Among the SINS criteria, a lytic tumor and the presence of a baseline VCF were identified as predictors of VCF in metastatic spinal segments. CONCLUSIONS In osteolytic or mixed lesions that were predominant in spinal metastases of CRC, the incidence of VCF was not negligible, even in patients treated with conventional spinal RT. This was especially evident in patients with spinal metastases with a SINS score ≥ 7. Presence of a baseline VCF after spinal RT is a predictor of VCF development and should be observed carefully.

Reirradiation spine stereotactic body radiation therapy for spinal metastases: systematic review.

OBJECTIVE Spinal metastases that recur after conventional palliative radiotherapy have historically been difficult to manage due to concerns of spinal cord toxicity in the retreatment setting. Spine stereotactic body radiation therapy (SBRT), also known as stereotactic radiosurgery, is emerging as an effective and safe means of delivering ablative doses to these recurrent tumors. The authors performed a systematic review of the literature to determine the clinical efficacy and safety of spine SBRT specific to previously irradiated spinal metastases. METHODS A systematic literature review was conducted, which was specific to SBRT to the spine, using MEDLINE, Embase, Cochrane Evidence-Based Medicine Database, National Guideline Clearinghouse, and CMA Infobase, with further bibliographic review of appropriate articles. Research questions included: 1) Is retreatment spine SBRT efficacious with respect to local control and symptom control? 2) Is retreatment spine SBRT safe? RESULTS The initial literature search retrieved 2263 articles. Of these articles, 160 were potentially relevant, 105 were selected for in-depth review, and 9 studies met all inclusion criteria for analysis. All studies were single-institution series, including 4 retrospective, 3 retrospective series of prospective databases, 1 prospective, and 1 Phase I/II prospective study (low- or very low-quality data). The results indicated that spine SBRT is effective, with a median 1-year local control rate of 76% (range 66%-90%). Improvement in patients' pain scores post-SBRT ranged from 65% to 81%. Treatment delivery was safe, with crude rates of vertebral body fracture of 12% (range 0%-22%) and radiation-induced myelopathy of 1.2%. CONCLUSIONS This systematic literature review suggests that SBRT to previously irradiated spinal metastases is safe and effective with respect to both local control and pain relief. Although the evidence is limited to low-quality data, SBRT can be a recommended treatment option for reirradiation.

Pushing the Dose to the Spinal Cord in Spine SBRT - Cord and Thecal Sac Dosimetric Correlation with Toxicity

Purpose/Objectives: Spine SBRT is widely performed and the reported risk of myelopathy is very low. Currently, guidelines vary on the maximum tolerable dose levels and designation of spinal cord vs thecal sac as the dose limiting structure. The current single institution study examines dose metrics to both structures and correlations with toxicity for patients treated with IMRT/VMAT. Materials/Methods: The radiation plans and DVH parameters were exported for 46 patients treated with SBRT for spinal metastases between April 2008 and December 2010 at the Mayo Clinic Rochester. Diagnostic MRI and where applicable, CT myelograms, from each patient were fused with the CT planning set and used to contour the spinal cord and the thecal sac. High resolution PRV structures were created in 1 mm increments for the cord (1-7 mm) and the thecal sac (1-2 mm), to examine dose gradients. Using an alpha/beta of 2 Gy, the biologically equivalent 2 Gy dose maximum (Max(2)[EQ2 Gy]) and high dose sub-volumes (Dxcc(2)[EQ2 Gy]) were calculated for xZ 0.1 cc to 1.0 cc in 0.1 cc increments from the dose volume histograms (DVHs). Toxicities for pain, nausea, myelitis, fatigue, fracture and radionecrosis were assessed (CTCAE v4.0). ROC analysis was used to define thresholds for constructing 2 x 2 contingency tables indicating toxicity using fisher exact test for significance (p < 0.01). Differences in mean values for groups with/without toxicity were assessed using t-tests for significance (p < 0.05). Results: Median values of Max(2)[EQ2 Gy] for the spinal cord and thecal sac were 38.5 (range, 7.9-67.9 Gy) and 67.7 Gy (range, 15.5-155.8 Gy), respectively. There were no cases of myelopathy (median follow-up 14 months). Median values for high dose sub volumes, Dxcc(2)[EQ2 Gy], were 2 times higher than the doses for 5% predicted grade 3 cord toxicity recommended by Sahgal et al. (IJORBP: 2013;85). Five patients had pain (4 with grade 1, 1 with grade 2). Four patients had nausea (3 with grade 1, 1 with grade 2). Cord D0.1cc(2)[EQ2 Gy] 23.8 Gy was significant (p Z 0.007) as an indicator for pain 1. Thecal sac D2.0cc(2)[EQ2 Gy] 29.3 Gy was significant (pZ 0.008) as an indicator for nausea 1. Distribution of Max(2)[EQ2 Gy] values for the thecal sac corresponded most closely to spinal cord + 3.5 mm margin. Median survival was 14 months (range 1-64 months). Conclusions: Current guidelines may overestimate the risk of myelopathy from spine SBRT. The current study’s population included patients who were both radiation naive and retreated after conventional palliative radiotherapy. The actual risk of myelopathy may be much lower than predicted. For patients with limited survival, it may be appropriate to allow higher doses to cord if it would be expected to result in better QOL/ functional outcomes/pain relief for the duration of their life. Author Disclosure: D. Owen: None. C.S. Mayo: None. L.S. Song: None. K. Ahmed: None. N.N. Laack: None. K.R. Olivier: None.

Nonsurgical oncological management of cancer pain

Pain is the most common symptom in patients with advanced cancer and often persists despite treatment. Recent advances in oncological therapy and the molecular basis of cancer and pain will help to improve patient outcomes. Chemotherapy, targeted therapy and radiotherapy are important components of the multidisciplinary management of cancer pain, which also includes early referral to specialist pain services. Cancer pain is complex and an understanding of the type of pain, the biology of the particular cancer as well as patient factors must be considered. Conventional palliative radiotherapy provides effective pain relief from cancer metastases, and recently radiopharmaceuticals have been shown to be beneficial for bone metastasis. Systemic cancer therapy can provide pain relief as a result of tumour shrinkage but recent studies suggest that benefit may also be as a consequence of modulation of pain signalling pathways. In advanced cancers, oncological therapies must be considered as anti-pain treatments. Identifying molecular targets that have a role in both pain and cancer is an interesting strategy for future drug development.

Stereotactic body radiotherapy: a new paradigm in the management of spinal metastases.

Spine stereotactic body radiotherapy is based on delivering high biologically effective doses to spinal metastases, with the intent to maximize both tumor and pain control. The purpose of this review is to outline the technical details of spine stereotactic body radiotherapy, contrast clinical outcomes to low biologically effective dose conventional palliative radiotherapy, discuss the role of surgery in the era of spine stereotactic body radiotherapy, and summarize the major serious adverse events that patients would otherwise not be at risk of with conventional radiotherapy.

Case Report: Grade 4 Radiation-Induced Colitis following Conventional Reirradiation to a Hip Metastasis

Palliative radiation therapy has been widely used for treatment of pain from metastatic bone disease. However, reirradiation is required in approximately 20% of patients initially treated with single fraction conventional palliative radiotherapy. There is a paucity of literature as to toxicities associated with reirradiation, and a lack of knowledge overall as to the cumulative dose limits for the organs at risk. We describe an uncommon late grade 4 adverse event of large bowel colitis in a patient initially radiated with 8 Gy in a single fraction, and reirradiated to the same area 3 months later with 20 Gy in 5 fractions due to pain progression.

Reirradiation Human Spinal Cord Tolerance for Stereotactic Body Radiotherapy

We reviewed the treatment for patients with spine metastases who initially received conventional external beam radiation (EBRT) and were reirradiated with 1-5 fractions of stereotactic body radiotherapy (SBRT) who did or did not subsequently develop radiation myelopathy (RM). Spinal cord dose-volume histograms (DVHs) for 5 RM patients (5 spinal segments) and 14 no-RM patients (16 spine segments) were based on thecal sac contours at retreatment. Dose to a point within the thecal sac that receives the maximum dose (P(max)), and doses to 0.1-, 1.0-, and 2.0-cc volumes within the thecal sac were reviewed. The biologically effective doses (BED) using α/β = 2 Gy for late spinal cord toxicity were calculated and normalized to a 2-Gy equivalent dose (nBED = Gy(2/2)). The initial conventional radiotherapy nBED ranged from ~30 to 50 Gy(2/2) (median ~40 Gy(2/2)). The SBRT reirradiation thecal sac mean P(max) nBED in the no-RM group was 20.0 Gy(2/2) (95% confidence interval [CI], 10.8-29.2), which was significantly lower than the corresponding 67.4 Gy(2/2) (95% CI, 51.0-83.9) in the RM group. The mean total P(max) nBED in the no-RM group was 62.3 Gy(2/2) (95% CI, 50.3-74.3), which was significantly lower than the corresponding 105.8 Gy(2/2) (95% CI, 84.3-127.4) in the RM group. The fraction of the total P(max) nBED accounted for by the SBRT P(max) nBED for the RM patients ranged from 0.54 to 0.78 and that for the no-RM patients ranged from 0.04 to 0.53. SBRT given at least 5 months after conventional palliative radiotherapy with a reirradiation thecal sac P(max) nBED of 20-25 Gy(2/2) appears to be safe provided the total P(max) nBED does not exceed approximately 70 Gy(2/2), and the SBRT thecal sac P(max) nBED comprises no more than approximately 50% of the total nBED.

Poor-Prognosis Patients with Cancer Metastatic to Brain: Implications for Stereotactic Radiosurgery

The risk of brain recurrence after whole-brain radiotherapy for metastatic disease has been infrequently reported, but quoted to be as high as 50%. These values are in the context of autopsy series or clinical trials and thus may not represent experience in routine clinical practice. This retrospective analysis was undertaken: (1) to confirm recursive analysis-based prognostic factors contributing to survival; and (2) to investigate efficacy of Gamma Knife Stereotactic Radiosurgery (GKSRS) in the poorest prognosis population. The records of 85 unselected, consecutive patients receiving whole-brain radiotherapy for brain metastases at Naval Medical Center San Diego were analyzed. Median dose of whole brain radiotherapy was 30 Gy in 10 fractions. These records were categorized by Radiation Therapy Oncology Group (RTOG) categories based on several prognostic factors. Further, analysis of 153 consecutive patients (178 treatments of 396 lesions) receiving GKSRS at the San Diego Gamma Knife Center was made for patients with Karnofsky Performance Status (KPS) < 70 (RTOG class 3). Twenty patients were identified. Median dose of GKSRS was 17.5 Gy at the 61% mean isodose line for all GKSRS patients. Six patients experienced clinical brain recurrences after whole-brain radiotherapy; the actuarial risk of clinical brain recurrence after whole-brain radio therapy approached 30% at 3 years, although few patients survived this long. Survival of patients after whole brain radiotherapy alone by RTOG category mirrored findings of other centers. Patients in class 3 (n = 26) had a median survival in our population of 59 days. For the 20 GKSRS patients with similar performance status and clinical follow-up, the median survival was longer, but not significantly so (162 days; p = 0.467). In the off-protocol setting, clinical brain recurrence of metastatic disease after whole-brain radiotherapy occurs not infrequently in patients with otherwise long survival. The RTOG criteria well describes an extremely poor-prognosis group of patients for whom the single fraction of stereotactic radiosurgery may optimize palliation as well as or better than longer courses of conventional palliative radiotherapy.

A comparison of two radiotherapy regimens for the treatment of symptoms from advanced bladder cancer

Pain and haematuria are two of the most distressing symptoms in patients with advanced bladder cancer. The aim of palliative radiotherapy is to relieve these symptoms with the minimum of stress to the patient and with minimal side effects. Two treatment regimens were studied: hypofractionated radiotherapy giving 1700 cGy in two fractions over 3 days and conventional palliative radiotherapy giving 4500 cGy in 12 fractions over 26 days. This study assesses 41 patients, all with Grade II–III T 3–4 transitional cell carcinomas of the bladder treated between 1982 and 1989, presenting with haematuria and local pain. Two-fraction (hypofractionated) treatment was given to 22 patients and conventional palliative radiotherapy to 19; patients were selected by performance status. The effect on haematuria was assessed as cleared, intermittent or persistent. Pain was assessed by noting reduction in the need for opiate analgesia. Any side effect was recorded. In the patients receiving two-fraction radiotherapy, 59% had clearance of the haematuria and in 73% there was improvement of their pain, compared with 16% and 37% respectively in those receiving conventional palliation. Survival of the two groups was 9.77 months and 14.47 months respectively. Side effects were trivial in both regimens. Radiotherapy given in two fractions for patients in poor general health is well tolerated and less distressing than the standard palliative regimen with 12 fractions. Haematuria and pain were more effectively palliated than with conventional treatment, though survival was shorter. We conclude that hypofractionated radiotherapy may be the palliative treatment of choice and the study supports the need for a prospective assessment of this treatment approach.