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  • Dec 20, 2019
    Patient-reported outcomes -- different RT schedules have similar effects metastatic epidural spinal cord compression

    The SCORE-2 trial compared 4 Gy x 5 (n=101) to 3 Gy x 10 (n=102) for metastatic epidural spinal cord compression (MESCC). The initial study found that the 4 Gy x 5 regimen was not inferior with regard to overall response (improvement or no further progression of motor deficits), ambulatory status, local PFS, and OS. This update reports patient-reported outcomes (relief of pain and distress). 

    Distress was measured using the distress thermometer (0=no; 10=extreme distress) and pain was assessed with a self-rating scale (0=no; 10=worst pain). Complete pain relief was defined as achieving a score of 0 points and partial pain relief as a decrease of 2 or more points, without an increase in analgesic use. 

    Distress and pain data were available from 100 of the 101 patients in the 4 Gy x 5 group and 100 of the 102 patients in the 3 Gy x 10 group. For distress, median scores were 8 points in both groups. The most common reasons were impairment in getting around/loss of mobility (99% vs 98%), pain (87% vs 94%) and fatigue (72% vs 78%) in the 4 Gy x 5 and 3 Gy x 10 groups, respectively. At 1 month, relief of distress was described by 58.1% and 62.7% of patients (p=0.25). For pain, median scores were 7 in both groups. At 1 month, complete pain relief was seen in 23.5% vs 20% in the 4 Gy x 5 and 3 Gy x 10 groups, respectively (p<0.001) and overall pain relief was 52.9% vs 57.1% (p=0.29). 

    Pain and distress relief in patients with MESCC with poor to intermediate survival prognosis receiving 4 Gy x 5 appears noninferior to 3 Gy x 10.  

    Reference (PubMed Link): Rades D, Segedin B, Conde-Moreno AJ, et al. Patient-reported outcomes-secondary analysis of the score-2 trial comparing 4 gy x 5 to 3 gy x 10 for metastatic epidural spinal cord compression. Int J Radiat Oncol Biol Phys 2019;105:760-764.

    Key Institution: University of Lubeck, Lubeck, Germany
    Keywords: Epidural Cord Compression; Radiation: Palliative; Stereotactic 

  • Dec 20, 2019
    Single-fraction SBRT for spine metastases with spinal canal compression not clearly different from 5-fraction treatment

    This article describes a randomized trial that was conducted to evaluate whether single-fraction radiotherapy is non-inferior to 5 fractions of radiotherapy for the treatment of malignant spinal cord compression. The endpoint used in this study was mobility. The trial was conducted in the United Kingdom and Australia and called SCORAD (single-fraction radiotherapy compared to multi-fraction radiotherapy).

    This trial randomized 694 patients, of which 686 were eligible for inclusion. The two arms included external beam radiation with single-fraction (8 Gy) or multi-fraction (20 Gy in 5 fractions over 5 consecutive days). Of the patients included in the trial, 44% had prostate cancer, 19% had lung cancer, and 12% had breast cancer.

    The primary endpoint for the trial, 8-week ambulatory response, was available for 49.9% of the patients, and was not significantly different between the two groups; grade 1 or 2 ambulatory status was achieved in 69.3% of patients in the single-fraction group and in 72.7% of patients in the multi-fraction group (p value for non-inferiority = 0.06). On secondary endpoint analysis, the rate of additional treatment for cancer within 12 months was not significantly different between the two groups (which included chemotherapy, hormone therapy, radiotherapy, or surgery). There was no statistically significant difference in survival between the groups. With respect to adverse events, the rate of grade 3 or 4 adverse events was not different between the two groups. In total 11 secondary end points were analyzed and none of these endpoints showed statistically significant differences.

    Authors concluded that single-fraction radiotherapy compared to multi-fraction radiotherapy did not meet the criterion for non-inferiority for the primary endpoint of ambulatory response status of grade 1 or 2 at 8 weeks. However, the authors point out that this is because the lower bound of the confidence Interval (CI, -11.5%) overlapped with the non-inferiority margin of -11%, and that the CI limits were within the non-inferiority margin for all of the other time points examined. Thus, the authors conclude that the observed risk differences between single-fraction and multi-fraction radiotherapy is small and unlikely to be of clinical importance.

    The relevance of this clinical trial is that single-fraction radiotherapy may be as effective as multi-fraction radiotherapy. Single-fraction radiotherapy also has advantages over multi-fraction radiotherapy, including more convenient for patients and less expensive. One caveat was that patients in the single-fraction group had more bladder toxicity--the 5-fraction regimen should be considered for at-risk patients.

    Reference (PubMed Link): Hoskin PJ, Hopkins K, Misra V, et al. Effect of single-fraction vs multifraction radiotherapy on ambulatory status among patients with spinal canal compression from metastatic cancer: The scorad randomized clinical trial. Jama 2019;322:2084-2094.

    Key Institution: CRUK & UCL Cancer Trials Centre, London, United Kingdom
    Keywords: spinal cord compression; metastasis; single-fraction; multi-fraction; 

  • Aug 20, 2019
    Radiotherapy for oligometastatic prostate cancer: Johns Hopkins Experience

    At present, we have evidence to suggest improvement in survival with prostate-directed radiation to patients with low-volume (but not high-volume) metastatic prostate patients, as informed by the STAMPEDE trial. We additionally have evidence from a non-prostate oligometastatic population that aggressive treatment of all metastatic disease –  in comparison to the primary site – derives a survival benefit (SABR-COMET).  

    This single-institution study retrospectively reports on their experience in treatment of 156 patients with oligometastatic prostate cancer between 2013 and 2018. Approximately three-quarters of patients had received prior definitive treatment for their disease. The remaining patients with de novo metastatic disease received prostate-directed radiation in addition to metastasis-directed radiation under this study. 94% of patient had 5 or less metastatic lesions treated, with a median of 2. The most common sites were bone (54%) and nodes (43%). Metastatic-directed therapy was nearly all delivered by stereotactic ablative radiation therapy (SABR) technique. 

    Median biochemical progression-free survival was greater than one year and local failure rate was 8% at 24 months.  On multivariable analysis, they identified that peri-radiotherapy androgen deprivation therapy (ADT), smaller GTV, and hormone-sensitive cancer was associated with prolonged biochemical progression-free survival (BPFS). Notably, of the 28 men with hormone-sensitive prostate cancer treated with peri-radiotherapy ADT, 20 had not progressed and median BPFS had not been reached at median follow up of 33.5 months. 

    Treatment was very well tolerated, with all acute toxicities (41% of patients) being f grade 2 or below, and only 9% of patients experienced late toxicity.  

    This study represents the largest single institutional study of men with oligometastatic prostate cancer treated with definitive radiotherapy to oligometastatic lesions. Due to the size of their analyzed cohort, they could probe deeply into variables that can help select those patients who might most benefit from aggressive metastatic directed therapy, in particular demonstrating sustained disease response in hormone-sensitive men treated with peri-RT ADT. Largely, their findings advocate for aggressive management of men with oligometastatic prostate cancer. 

    Limitations include a single institution experience in which 92% of cases were treated by a single physician, limiting the generalizability of their results. The study was retrospective, which can contribute to inherent bias and confounding variables. Further prospective, multi-institutional studies will be needed to confirm these findings. 

    (Open Access)

    Reference (PubMed Link): Deek MP, Yu C, Phillips R, et al. Radiation therapy in the definitive management of oligometastatic prostate cancer: The johns hopkins experience. Int J Radiat Oncol Biol Phys 2019;105:948-956.

    Key Institution: Johns Hopkins University School of Medicine
    Keywords: Stereotactic body radiotherapy (SBRT), stereotactic ablative radiation therapy (SABR) oligometastasis, prostate cancer, definitive treatment

  • Jul 20, 2019
    Durability of pain response after conventional palliative irradiation of nonspine bone metastases

    The Dutch Bone Metastasis Study is a pivotal study from the 1990s that validated the use of single fraction (8 Gy) conventional palliative radiation for painful nonspine bone metastases. Compared to conventional multifraction regimen (24 Gy in 6 fractions), pain relief was similar although retreatment rate was ~3x higher for single fraction. However, the higher retreatment rate may be in part due to physician bias, given higher likelihood/lower threshold to retreat after a single fraction than multifraction.   

    This study by Spencer et al used longitudinal questionnaires from the Dutch Bone Metastasis Study to evaluate net pain relief (NPR: proportion of remaining life spent with pain response) of the two regimens. Given there has been increasing interest in using SBRT for theoretically more rapid/durable/better pain relief, further evaluation of external beam irradiation is necessary to compare the two techniques head to head. Spencer et al show that in the ~70% of patients who experienced at least partial pain relief, NPR was ~56%. There was no difference between the two regimens unless excluding response after re-treatment (then NPR was 49 vs 57% in single vs multifraction). The clinical significance of this difference is not clear given a re-irradiation event may not directly correlate with pain severity (see physician caveat above).  

    This study proposed NPR as a tool for quantifying pain relief (useful for objectively comparing different fractionation regimens and techniques in future studies), and further validates use of single fraction regimen given similarity in net pain relief to multifraction (in context of caveats stated above) with greater cost-effectiveness and patient convenience.  

    (Open Access)

    Reference (PubMed Link): Spencer K, Velikova G, Henry A, et al. Net pain relief after palliative radiation therapy for painful bone metastases: A useful measure to reflect response duration? A further analysis of the dutch bone metastasis study. Int J Radiat Oncol Biol Phys 2019;105:559-566.

    Key Institution: Leeds Institute of Medical Research/University of Leeds, Leeds, UK
    Keywords: Bone metastases, 3D conformal, conventional palliative radiation, durability of pain relief

  • Jul 30, 2018
    Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial

    The question of how aggressively to treat oligometastatic disease, and whether or not there is a benefit to doing so, is an evolving paradigm in multiple disease sites. This is of particular importance in primary histologies with a long natural history, such as breast and prostate cancer, where patients may live for years with a diagnosis of metastatic disease. These authors report on the results of a Phase II, multi-center study in which patients with asymptomatic patients with prostate cancer and fewer than 4 extracranial metastases were randomized to either surveillance or metastasis-directed therapy (MDT) at all detected lesions (using either surgery or stereotactic body radiotherapy). The primary endoint was androgen-deprivation free survival, and ADT was started at symptomatic progression, progression to more than 3 metastases, or local progression of known metastases. This study enrolled 62 patients, with 31 patients in each arm. The median ADT-free survival time was 13 months for patients in the surveillance arm and 21 months in the MDT arm (HR 0.60, 80% CI 0.40 –0.90). There were no symptomatic or local progression events observed in the MDT group, whereas 3 and 6 events occurred in the surveillance arm, respectively. The authors conclude that MDT is safe and effective compared to surveillance.
    This is an important study that provides support of metastasis-directed therapy for oligometastatic disease. Metastasis-directed therapy has become more common in recent years, particularly as SBRT becomes more widely used and available. 

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    Journal & Date: Journal of Clinical Oncology 36, no. 5 (February 2018) 446-453.
    Key Institution: Ghent University Hospital, Ghent, Belgium
    Keywords: Oligometastatic disease, prostate cancer, metastasis-directed therapy

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