Time Developing Motor Deficits Research Articles

A New Scoring Tool to Estimate Post-Treatment Ambulatory Status after Radiotherapy of Metastatic Spinal Cord Compression

<h3>Purpose/Objective(s)</h3> To improve treatment personalization of patients irradiated for metastatic spinal cord compression (MSCC), a score predicting post-treatment ambulatory status after radiotherapy (RT) alone (without surgery) was presented in 2008. Since then, upfront decompressive surgery has become more popular, which may decrease the predictive value of this score. A new scoring tool may be helpful. <h3>Materials/Methods</h3> Data of 283 patients treated with RT alone for MSCC in three prospective trials since 2010 were re-evaluated. Dose-fractionation of RT and 12 factors were analyzed including age (<=67 <i>vs</i> >67 years), gender, tumor type (breast ca. <i>vs</i> prostate ca. <i>vs</i> myeloma/lymphoma <i>vs</i> lung ca. <i>vs</i> others), interval from tumor diagnosis to MSCC (<=6 <i>vs</i> >6 months), number of affected vertebrae (1-2 <i>vs</i> >=3), further bone lesions (no <i>vs</i> yes), visceral metastases (no <i>vs</i> yes), time developing motor deficits (<=7 <i>vs</i> >7 days), pre-RT ambulatory status (ambulatory without aid <i>vs</i> ambulatory with aid <i>vs</i> not ambulatory), performance score (ECOG-PS 1-2 <i>vs</i> 3-4), sensory deficits (no <i>vs</i> yes), and sphincter dysfunction (no <i>vs</i> yes). For each factor that achieved significance in the multivariate analysis (logistic regression model) after backward regression modelling, scoring points were calculated by dividing the post-RT ambulatory rates (in %) by 10. The scoring points of these factors were added for each patient. The new score was compared to the previous tool for prediction (positive predictive value, PPV) of ambulatory and non-ambulatory status after RT. <h3>Results</h3> In the multivariate analysis, primary tumor type (p=0.010), sensory deficits (p=0.002), sphincter dysfunction (p=0.017), pre-RT ambulatory status (p<0.001) and ECOG-PS (p<0.001) were significant; a trend was found for the time developing motor deficits (p=0.054). Five of these factors were included in the score and available for 278 patients. ECOG-PS was not included, since ambulatory status and ECOG-PS were confounding variables. For internal validation, bootstrapping with 1000 replications was used. Corrected C-statistic accounting for overfitting was 0.91, which demonstrated good predictive performance of the model. Based on post-RT ambulatory rates, three prognostic groups (25-29, 30-38 and 39-45 points) were designed with ambulatory rates of 11% (5/44), 64% (49/77) and 97% (152/157), respectively. Rates of local control of MSCC were 100%, 82% and 94% at 1 year, and 100%, 82% and 87% at 2 years. Survival rates were 20%, 21% and 55% at 1 year, and 13%, 12% and 39% at 2 years. PPVs of the new score to predict ambulatory and non-ambulatory status were 97% and 89% <i>vs</i> 98% and 79% when using the previous score. <h3>Conclusion</h3> The new score appeared more precise than the previous one in predicting non-ambulatory status after RT. Depending on survival prognosis, patients with <=38 points likely benefit from upfront surgery. Since patients of the 39-45 points group had very high rates of post-RT ambulatory status and local control, they may not require surgery.

Identifying patients with malignant spinal cord compression (MSCC) near end of life who can benefit from palliative radiotherapy

BackgroundA previous score predicted death ≤ 2 months following radiotherapy for MSCC. For patients with a high probability of early death, best supportive care was recommended. However, some of these patients may benefit from radiotherapy regarding preservation or improvement of motor function. To identify these patients, an additional score was developed.MethodsPre-treatment factors plus radiotherapy regimen were retrospectively evaluated for successful treatment (improved motor function or remaining ambulatory without aid) and post-treatment ambulatory status in 545 patients who died ≤ 2 months. Factors included age, interval from tumor diagnosis until MSCC, visceral metastases, further bone metastases, primary tumor type, sex, time developing motor deficits, pre-treatment ambulatory status, and number of affected vertebrae. Factors significant on both multivariable analyses were included in the score (worse outcomes 0 points, better outcomes 1 point).ResultsOn multivariable analyses, myeloma/lymphoma, time developing motor deficits > 14 days, and pre-treatment ambulatory status were significantly associated with both successful treatment and ambulatory status, affection of 1–2 vertebrae with successful treatment only. On univariable analyses, 1 × 8 and 5 × 4 Gy were not inferior to 5 × 5 Gy and longer-course regimens. Considering the three factors significant for both endpoints, three groups were designed (0, 1, 2–3 points) with treatment success rates of 4%, 15% and 39%, respectively (p < 0.0001), and post-treatment ambulatory rates of 4%, 43% and 86%, respectively (p < 0.0001).ConclusionThis score helps identify patients with MSCC who appear to benefit from palliative radiotherapy in terms of improved motor function or remaining ambulatory in spite of being near end of life.

A New Clinical Instrument for Estimating the Ambulatory Status after Irradiation for Malignant Spinal Cord Compression.

Simple SummarySince 2005, upfront surgery has been increasingly used in addition to radiotherapy for patients with malignant spinal cord compression (MSCC). As spinal surgery includes significant risks, careful patient selection is crucial. Individual risks and benefits should be considered when choosing an optimal treatment strategy. Benefits include preserving or regaining a patient’s ambulatory function. To facilitate the decision pro or contra upfront surgery, a new prognostic score was developed to predict ambulatory status after radiotherapy alone. This clinical score was created from data of patients previously treated in prospective trials. It includes three prognostic groups (17–21, 22–31, and 32–37 points) with post-radiotherapy ambulatory rates of 10%, 65%, and 97%, respectively. Patients of the 32–37 points group may not require upfront surgery. The new instrument achieved very high accuracy in predicting post-radiotherapy ambulatory and non-ambulatory status and was more precise than a previous prognostic score in predicting non-ambulatory status.Estimating post-treatment ambulatory status can improve treatment personalization of patients irradiated for malignant spinal cord compression (MSCC). A new clinical score was developed from data of 283 patients treated with radiotherapy alone in prospective trials. Radiotherapy regimen, age, gender, tumor type, interval from tumor diagnosis to MSCC, number of affected vertebrae, other bone metastases, visceral metastases, time developing motor deficits, ambulatory status, performance score, sensory deficits, and sphincter dysfunction were evaluated. For factors with prognostic relevance in the multivariable logistic regression model after backward stepwise variable selection, scoring points were calculated (post-radiotherapy ambulatory rate in % divided by 10) and added for each patient. Four factors (primary tumor type, sensory deficits, sphincter dysfunction, ambulatory status) were used for the instrument that includes three prognostic groups (17–21, 22–31, and 32–37 points). Post-radiotherapy ambulatory rates were 10%, 65%, and 97%, respectively, and 2-year local control rates were 100%, 75%, and 88%, respectively. Positive predictive values to predict ambulatory and non-ambulatory status were 97% and 90% using the new score, and 98% and 79% using the previous instrument. The new score appeared more precise in predicting non-ambulatory status. Since patients with 32–37 points had high post-radiotherapy ambulatory and local control rates, they may not require surgery.

Prognostic Value of Preclinical Markers after Radiotherapy of Metastatic Spinal Cord Compression-An Additional Analysis of Patients from Two Prospective Trials.

Simple SummaryFor personalized treatment of metastatic spinal cord compression (MSCC), a patient’s remaining lifespan plays an important role, which can be estimated using prognostic factors. This study used data from 190 patients with poor or intermediate survival prognoses previously included in prospective trials to evaluate the prognostic role of preclinical markers including hemoglobin, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase (LDH), and c-reactive protein (CRP) plus clinical factors. On univariate analyses, NLR, LDH, CRP, and clinical factors tumor type, ambulatory status, and sphincter function were significantly associated with survival. On multivariate analysis, LDH, CRP, tumor type, and ambulatory status proved to be independent predictors of survival. In addition to clinical factors, preclinical markers may support physicians to estimate survival prognoses and contribute to the treatment personalization of patients with MSCC.For optimal personalization of treatment for metastatic spinal cord compression (MSCC), the patient’s survival prognosis should be considered. Estimation of survival can be facilitated by prognostic factors. This study investigated the prognostic value of pre-treatment preclinical markers, namely hemoglobin, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase (LDH), and c-reactive protein (CRP), in 190 patients from two prospective trials who had poor or intermediate survival prognoses and were irradiated for MSCC with motor deficits. In addition, clinical factors including radiation regimen, age, gender, tumor type, interval from tumor diagnosis to MSCC, number of affected vertebrae, visceral metastases, other bone metastases, time developing motor deficits, ambulatory status, sensory function, and sphincter function were evaluated. On univariate analyses, NLR (p = 0.033), LDH (p < 0.001), CRP (p < 0.001), tumor type (p < 0.001), pre-radiotherapy ambulatory status (p < 0.001), and sphincter function (p = 0.011) were significant. In the subsequent Cox regression analysis, LDH (p = 0.007), CRP (p = 0.047), tumor type (p = 0.003), and ambulatory status (p = 0.010) maintained significance. In addition to clinical factors, preclinical markers may help in estimating the survival of patients irradiated for MSCC. Additional prospective trials are warranted.

A New and Easy-to-Use Survival Score for Patients Irradiated for Metastatic Epidural Spinal Cord Compression

PurposeA survival score was created in 2008 to improve treatment personalization of patients irradiated for metastatic epidural spinal cord compression (MESCC). Since then, targeted therapies improved survival of patients with cancer, which may decrease this score's predictive value. A new score appears necessary. Methods and MaterialsTwo hundred sixty-four patients receiving radiation therapy without surgery in prospective trials (2010-2021) were included. A dose-fractionation regimen plus 15 factors were analyzed: age, sex, tumor type, interval tumor diagnosis to MESCC, MESCC sites, affected vertebrae, additional bone lesions, other distant lesions (yes or no), number of organs involved by metastases, time developing motor deficits, ambulatory status, sensory function, sphincter dysfunction, pain, and distress. Six-month survival rates (%) of independent prognostic factors were divided by 10 and summed for each patient. The score was compared with the previous tool for predicting death ≤6 months and survival ≥6 months. ResultsIn a multivariate analysis, tumor type (P = .001), other distant lesions (P < .001), and ambulatory status (P < .001) were significant. Based on 6-month survival rates, 4 groups (8-9, 10-13, 14-17, and 18 points) were created with 6-month survival rates of 12.8%, 34.7%, 62.8%, and 90.0%, respectively (version A). For version B, “other distant lesions” was replaced by “number of organs involved by metastases.” Version B included 4 groups (8-10, 11-14, 15-16, and 17 points) with 6-month survival rates of 11.1%, 42.0%, 68.6%, and 91.7%, respectively. Positive predictive values to predict death ≤6 months were 87.2% (version A) and 88.9% (version B) versus 76.6% (3 groups) and 84.6% (5 groups) for the previous score. Positive predictive values to predict survival ≥6 months were 90.0% and 91.7% versus 59.0% and 64.3%. ConclusionsBoth versions of the new score were more precise than the previous tool. Version B appears slightly superior to version A but requires more extensive diagnostic staging that may not be readily available when emergently treating.

Radiotherapy with or without Decompressive Surgery for Metastatic Spinal Cord Compression: A Retrospective Matched-Pair Study Including Data from Prospectively Evaluated Patients.

Simple SummaryIn a retrospective matched-pair study including data of prospectively evaluated patients who were treated for metastatic spinal cord compression, 79 patients assigned to surgery plus radiotherapy were compared to 79 patients receiving radiotherapy alone. Improvement of motor function occurred more significantly often after surgery plus radiotherapy, whereas no significant differences were found for post-treatment ambulatory rates, local progression-free survival, overall survival, and freedom from in-field recurrence. Ten patients died within 30 days after radiotherapy alone and 12 patients within 30 days after surgery. More than one third of surgically treated patients did not complete their radiotherapy due to early death or decreased performance score following surgery. Thus, when selecting a patient for upfront surgery, the individual patient’s prognosis must be considered and weighed against the risk of perioperative complications and 30-day mortality.In 2005, a randomized trial showed that addition of surgery to radiotherapy improved outcomes in patients with metastatic spinal cord compression (MSCC). Since then, only a few studies compared radiotherapy plus surgery to radiotherapy alone. We performed a retrospective matched-pair study including data from prospective cohorts treated after 2005. Seventy-nine patients receiving radiotherapy alone were matched to 79 patients assigned to surgery plus radiotherapy (propensity score method) for age, gender, performance score, tumor type, affected vertebrae, other bone or visceral metastases, interval tumor diagnosis to MSCC, time developing motor deficits, and ambulatory status. Improvement of motor function by ≥1 Frankel grade occurred more often after surgery plus radiotherapy (39.2% vs. 21.5%, p = 0.015). No significant differences were found for post-treatment ambulatory rates (59.5% vs. 67.1%, p = 0.32), local progression-free survival (p = 0.47), overall survival (p = 0.51), and freedom from in-field recurrence of MSCC (90.1% vs. 76.2% at 12 months, p = 0.58). Ten patients (12.7%) died within 30 days following radiotherapy alone and 12 patients (15.2%) died within 30 days following surgery (p = 0.65); 36.7% of surgically treated patients did not complete radiotherapy as planned. Surgery led to significant early improvement of motor function and non-significantly better long-term control. Patients scheduled for surgery must be carefully selected considering potential benefits and risk of perioperative complications.

Comparison of 5\u2009\xd7\u20095\xa0Gy and 10\u2009\xd7\u20093\xa0Gy for metastatic spinal cord compression using data from three prospective trials

BackgroundIn a palliative situation like metastatic spinal cord compression (MSCC), overall treatment time of radiotherapy should be as short as possible. This study compared 5 × 5 Gy in 1 week to 10 × 3 Gy in 2 weeks in a prospective cohort.MethodsForty patients receiving 5 × 5 Gy in a phase II trial were matched 1:2 to 213 patients receiving 10 × 3 Gy in two previous prospective studies for tumor type, ambulatory status, time developing motor deficits, interval between tumor diagnosis and MSCC and visceral metastases. These factors were consistent in all three patients (triple) used for each 1:2 matching. Groups were compared for local progression-free survival (LPFS), motor function, ambulatory status, and overall survival (OS).ResultsAfter matching, 32 triples remained for analyses (N = 96 in total). Six-month LPFS-rates were 94% after 5 × 5 Gy and 87% after 10 × 3 Gy (p = 0.36), 6-month OS-rates 43% and 35% (p = 0.74). Improvement of motor function was achieved in 59% and 34% of patients (p = 0.028); overall response rates (improvement or no further progression of motor deficits) were 94% and 89% (p = 0.71). Post-treatment ambulatory rates were 81% after 5 × 5 Gy and 85% after 10 × 3 Gy (p = 0.61). Of non-ambulatory patients, 50% (6/12) and 46% (11/24) regained the ability to walk (p = 1.00).Conclusions5 × 5 Gy in 1 week appeared similarly effective as 10 × 3 Gy in 2 weeks. These results may not be applicable to long-term survivors and should be confirmed in a randomized trial directly comparing 5 × 5 Gy and 10 × 3 Gy.Trial registration clinicaltrials.gov NCT03070431. Registered 27 February 2017.

Predictors of Outcomes and a Scoring System for Estimating Survival in Patients Treated With Radiotherapy for Metastatic Spinal Cord Compression From Small-Cell Lung Cancer

PurposeTo identify prognostic factors and create a survival score to facilitate individualized care of patients with metastatic spinal cord compression (MSCC) from small-cell lung cancer (SCLC). Patients and MethodsRadiation regimen plus 9 factors were retrospectively evaluated in 120 patients irradiated for MSCC from SCLC for overall response, improvement of motor deficits, postradiotherapy ambulatory status, local control of MSCC, and overall survival (OS). Factors included age, interval diagnosis of SCLC to radiotherapy (RT) of MSCC, visceral metastases, further bone metastases, gender, time developing motor deficits, pre-RT ambulatory status, number of affected vertebrae, and Eastern Cooperative Oncology Group performance status (ECOG PS). ResultsImprovement of motor deficits showed significant associations with ECOG PS 1-2 (P = .018); time developing motor deficits achieved borderline significance (P = .059). Post-RT ambulatory status was significantly associated with slower development of motor dysfunction (P = .003), ambulatory status (P < .001), and ECOG PS 1-2 (P < .001). No factor was significantly associated with overall response and local control. On multivariate analysis, OS was significantly associated with interval from SCLC diagnosis to RT of MSCC (P = .004), visceral metastases (P < .001), ambulatory status (P = .002), and ECOG PS (P = .002). For the survival score, 6-month OS rates related to each of these factors were divided by 10. Patient scores were obtained by adding these factors' scores. Three groups were defined (5, 7-13, and 15-17 points) with 6-month OS rates of 0, 18%, and 77%, respectively (P < .001). ConclusionPredictors of various outcomes were identified and a survival score was created that can support physicians aiming to create personalized treatments to patients with MSCC from SCLC.

Prognostic factors of moter function after surgery for patients with metastatic spinal cord compression: a multicenter retrospective cohort stduy

Objective To identify prognostic factors ofmotorfunctionafter surgery of metastatic spinal cord compression (MSCC). Methods The clinical data of 681 patients with spinal metastases from January 2008 to December 2017 were retrospectively analyzed.According to inclusion and exclusion criteria, a total of 206 patients with spinal metastatic were included. Postoperative neurological function was assessed using Frankel classification.The influence of age, gender, preoperative status, number of spine metastases, location of spinal metastases, visceral metastases, bone metastases, primary tumor type,interval from symptom to surgery,time of developing motor deficits,interval from primary tumor diagnosis to MSCC,preoperativethe Eastern Cooperative Oncology Group performance status (ECOG-PS), Karnofsky Performance score (KPS) and surgical procedures on postoperative function outcomes were explored. Results 140 (68.0%) patients were able to walk postoperatively compared with 88 (42.7%) patients preoperatively. Moreover, in 89.8% of all patients, 79 ambulatory patients maintained ambulation after treatment. The univariate analysis according to Ordered-logit model showed thatnumber of spine metastases, location of spinal metastases, preoperative ECOG-PS, preoperative KPS, interval from symptom to surgery and time of developing motor deficits were related with post-treatment motor functions. The multivariable analysis showed that number of spine metastases (OR=2.03; 95%CI: 1.12-3.33; P=0.04), preoperative ECOG-PS (OR=4.84; 95%CI: 2.42-8.15; P=0.038), interval from symptom to surgery (OR=3.78;95%CI: 3.12-9.15;P=0.024), time of developing motor deficits(OR=2.75;95%CI:1.22-3.89;P=0.01) were independent prognostic factors for function outcomes. Conclusion 1-2 levels of metastasis,Interval from symptom to treatment ≥ 48 h, time of developing motor deficits ≥7 d, and ECOG-PS 1-2 can be considered as the most significant positive prognosticfactors for post-treatment ambulatory status. Spinal metastasis should have a higher priority, and immediate intervention should be started before the development of irreversible neurologic deficits. Increasing awareness of early symptoms and earlier screeningwith regular outpatient review might make a difference for patients with MSCC. Consequently, the identified prognostic factors can be considered as apreoperative assessment tool to predict the neurologic outcomeand guide clinical treatment for individual patients with MSCC. Key words: Spinal cord compression; Locomotion; Prognosis

A scoring system to predict local progression-free survival in patients irradiated with 20\u2009Gy in 5 fractions for malignant spinal cord compression

BackgroundLocal progression-free survival (LPFS = stable or improved motor function/resolution of paraplegia during RT without in-field recurrence following RT) is important when treating metastatic spinal cord compression (MSCC). An instrument to estimate LPFS was created to identify patients appropriately treated with short-course RT instead of longer-course RT plus/minus decompressive surgery.MethodsIn 686 patients treated with 20 Gy in 5 fractions alone, ten characteristics were retrospectively analyzed for LPFS including age, interval between tumor diagnosis and RT of MSCC, visceral metastases, other bone metastases, primary tumor type, gender, time developing motor deficits, pre-RT gait function, number of vertebrae affected by MSCC, and performance score. Characteristics significantly (p < 0.05) associated with LPFS on multivariate analyses were incorporated in the scoring system. Six-month LPFS rates for significant characteristics were divided by 10, and corresponding points were added.ResultsOn multivariate analyses, visceral metastases (p < 0.001), tumor type (p = 0.009), time developing motor deficits (p < 0.001) and performance score (p = 0.009) were associated with LPFS and used for the scoring system. Scores for patients ranged between 24 and 35 points. Three groups were designed: 24–28 (A), 29–31 (B) and 32–35 (C) points. Six-month LPFS rates were 46, 69 and 92%, 12-month LPFS rates 46, 63 and 83%. Median survival times were 2 months (61% died within 2 months), 4 months and ≥ 11 months (median not reached).ConclusionsMost group A patients appeared sub-optimally treated with 20 Gy in 5 fractions. Patients with survival prognoses ≤2 months may be considered for best supportive care or single-fraction RT, those with prognoses ≥3 months for longer-course RT plus/minus upfront decompressive surgery. Many group B and most group C patients achieved long-time LPFS and appeared sufficiently treated with 20 Gy in 5 fractions. However, based on previous data, long-term survivors may benefit from longer-course RT.

Outcomes After Radiotherapy Alone for Metastatic Spinal Cord Compression in Patients with Oligo-metastatic Breast Cancer.

Patients with oligo-metastatic breast cancer are a unique patient subgroup with more favourable outlook than most patients with metastatic disease. Prognostic factors in these patients with metastatic spinal cord compression (MSCC) were evaluated. In 159 patients irradiated for MSCC from oligo-metastatic breast cancer, seven characteristics were retrospectively analyzed including age, interval between breast cancer diagnosis and irradiation of MSCC, time developing motor deficits, ambulatory status, involved vertebrae, performance score (ECOG-PS) and radiotherapy regimen. Improvement of motor function was significantly associated with time developing motor deficits (p=0.017), post-radiotherapy ambulatory status with pre-radiotherapy ambulation (p=0.012) and ECOG-PS 1-2 (p=0.029). Radiation doses of 39-40 Gy (equivalent doses) resulted in 1- and 2-year local control of 100% and 95%. On multivariate analyses, higher doses were associated with local control (p=0.011). Pre-radiotherapy ambulatory status (p=0.001) and ECOG-PS 1-2 (p=0.002) were associated with survival. Significant prognostic factors were identified for patients with MSCC from oligo-metastatic breast cancer. Higher radiation doses improved local control.

1x8 Gy versus 5x4 Gy for metastatic epidural spinal cord compression: a matched-pair study of three prognostic patient subgroups

BackgroundThis study provides separate comparisons of 1 × 8 Gy to 5 × 4 Gy for metastatic epidural spinal cord compression (MESCC) in patients with poor, intermediate and favorable survival prognoses.MethodsPatients receiving 1 × 8 Gy were matched to patients receiving 5 × 4 Gy for age, gender, performance status, tumor type, involved vertebrae, other bone metastases, visceral metastases, interval between tumor diagnosis and MESCC, ambulatory status and time developing motor deficits. From a study including patients with poor (N = 156) or intermediate (N = 86) survival prognoses, subgroup analyses were performed. Furthermore, 232 new patients with favorable prognoses matched the same way were included.ResultsIn poor prognoses patients, 6-month survival rates were 10% after 1 × 8 Gy and 6% after 5 × 4 Gy (p = 0.38); in-field reRT rates in few patients alive at 6 months were 15 and 2% (p = 0.16). In intermediate prognoses patients, 6-month survival rates were 49% after 1 × 8 Gy and 58% after 5 × 4 Gy (p = 0.30). ReRT rates at 6 months were 23 and 13% (p = 0.25). In favorable prognoses patients, 6-month survival rates were 89% after 1 × 8 Gy and 91% after 5 × 4 Gy. ReRT rates at 6 months were 14 and 3% (p = 0.007). In no subgroup, RT regimen had a significant impact on motor function.ConclusionsSince in patients with poor prognoses, outcomes after 1 × 8 Gy and 5 × 4 Gy were not significantly different, 1 × 8 Gy may be an option. In patients with intermediate prognoses, a trend was found in favor of 5 × 4 Gy. In patients with favorable prognoses, need for in-field reRT was greater after 1 × 8 Gy.

Role of the overall treatment time of radiotherapy with 10×3Gy for outcomes in patients with metastatic spinal cord compression.

Radiotherapy alone still is the most commonly delivered treatment modality for metastatic spinal cord compression (MSCC). MSCC is an emergency situation, which requires treatment as soon as possible. When radiotherapy is performed with the most commonly used approach 10×3Gy (30Gy in 10 fractions) over 2weeks, the question has been asked whether an overall treatment time (OTT) of 14-15days including two weekends without irradiation leads to worse outcomes than OTT of 12days (beginning of radiotherapy on a Monday resulting in only one weekend break)? A total of 412 patients with MSCC were included in this retrospective study. Ninety-two patients receiving 10×3Gy over 12days were compared to 320 patients with an OTT of 14-15days. Ten additional factors were investigated. On multivariate analysis, functional outcome was associated with tumour type (P<0.001), time developing motor deficits (P<0.001), ambulatory status (P=0.018) and performance score (P<0.001); OTT had no significant impact (P=0.40). On univariate analysis of local control of MSCC (freedom from recurrence in irradiated spinal parts), no factor was significant including OTT (P=0.66). On multivariate analysis, visceral metastases (P<0.001), tumour type (P<0.001), time developing motor deficits (P<0.001), ambulatory status (P<0.001) and performance score (P<0.001) were associated with survival, OTT not even on univariate analysis (P=0.55). Since an OTT of 14-15days had no negative impact on outcomes compared to 12days, compensation in form of an additional radiation fraction or continuation of radiotherapy during weekends is not required, if radiotherapy cannot be started on a Monday.

Results of a multicenter study investigating the potential impact of the overall treatment time on outcomes of radiation therapy alone with 5×4 Gy for metastatic epidural spinal cord compression

Purpose/ObjectiveA 5×4 Gy program is commonly used for metastatic epidural spinal cord compression (MESCC). It is unclear whether an overall treatment time (OTT) of 5 days (5 consecutive fractions) results in better outcomes than an OTT of 7 days (ie, no irradiation during the weekend). Methods and materialsA total of 111 patients who received 5×4 Gy over 5 consecutive days were retrospectively compared with 277 patients treated with 5×4 Gy over 7 days (no irradiation during the weekend) for effect on motor function, local control of MESCC, and overall survival (OS). Ten further characteristics were evaluated: age, gender, interval tumor diagnosis to MESCC, visceral metastases, other bone metastases, primary tumor type, time developing motor deficits, walking ability, vertebrae involved, and performance status. ResultsOn multivariate analysis regarding post-radiation therapy motor function, primary tumor type (P = .011) and time developing motor weakness (P < .001) were significant, whereas the OTT did not even achieve significance on univariate analysis (P = .99). On multivariate analysis of local control, visceral metastases (P = .006) were significant. Again, the OTT was not even significant on univariate analysis (P = .81). On multivariate analysis of OS, interval tumor diagnosis to MESCC (P = .015), visceral metastases (P .001), tumor type (P = .003), walking ability (P < .001), and Eastern Cooperative Oncology Group performance score (P < .001) achieved significance. Even on univariate analysis, OTT did not have an effect on OS (P = .79). ConclusionsLonger OTT did not impair outcomes of irradiation with 5×4 Gy for MESCC; thus, no compensation (for example an additional radiation fraction) is necessary if the radiation treatment is not continued during the weekend.

A predictive tool particularly designed for elderly myeloma patients presenting with spinal cord compression.

BackgroundThis study was performed to design a predictive tool that allows the estimation of overall survival (OS) of elderly myeloma patients (aged ≥65 years) presenting with myeloma-induced spinal cord compression (SCC).MethodsOne-hundred-and-sixteen patients irradiated for motor deficits of the legs due to myeloma-induced spinal cord compression were retrospectively evaluated. Ten characteristics were analyzed for OS including age, interval between myeloma diagnosis and radiotherapy, other osseous myeloma lesions, myeloma type, gender, time developing motor deficits, number of affected vertebrae, ECOG-PS, pre-radiotherapy ambulatory status, and fractionation regimen. Characteristics that achieved significance on multivariate analysis were included in the predictive tool. The score for each characteristic was obtained from the 1-year OS rate divided by 10. The sum of these scores represented the prognostic score for each patient.ResultsOn multivariate analysis, myeloma type (hazard ratio 3.31; 95 %-confidence interval 1.75–6.49; p < 0.001), ECOG-PS (HR 5.33; 95 %-CI 2.67–11.11; p < 0.001), ambulatory status (HR 2.71; 95 % CI 1.65–4.57; p < 0.001), and age (HR 1.95; 95 % CI 1.03–3.78; p = 0.040) were significantly associated with survival. Sum scores ranged from 18 to 32 points. Based on the sum scores, three prognostic groups were designed: 18–19, 21–28 and 29–32 points. The corresponding 1-year survival rates were 0, 43 and 96 %, respectively (p < 0.001).ConclusionsThis new predictive tool has been specifically designed for elderly myeloma patients with SCC. It allows estimating the survival prognosis of this patient group and supports the treating physicians when looking for the optimal treatment approach for an individual patient.

Individual strategy for lung cancer patients with metastatic spinal cord compression

PurposeThe criteria for identifying lung cancer patients with metastatic spinal cord compression (MSCC) who may benefit from decompressive surgery remains unclear. This study aims to create a new therapeutic strategy which can guild surgeons to select the individual treatment for MSCC patients from lung cancer. MethodsWe retrospectively assessed 73 consecutive lung cancer patients who were treated with decompressive surgery for MSCC. Twelve preoperative characteristics were analyzed for postoperative survival. Characteristics significantly associated with survival in the multivariate analyses were included in a scoring system. The total score for each patient was obtained by adding the scoring points of all significant characteristics. Postoperative function outcome was also analyzed according to prognostic groups. ResultsIn the multivariate analyses, preoperative ambulatory status (P = 0.02), targeted therapy (P = 0.01), number of involved vertebrae (P < 0.01), visceral metastases (P < 0.01), and time developing motor deficits (P < 0.01) had significant impact on survival and were included in the scoring system. According to the prognostic scores, which ranged from 15 to 35 points, three prognostic groups were designed: 15–23 points (n = 32), 25–29 points (n = 26), and 31–35 points (n = 15). The corresponding median survival times were 2.6 months (95% CI, 1.5–4.3 months), 7.2 months (95% CI, 6.0–10.8 months) and 13.2 months (95% CI, 8.8–18.7 months), respectively (P < 0.01), and the corresponding postoperative ambulatory rates were 46.9%, 80.8%, and 93.3%, respectively (P < 0.01). ConclusionWe present a scoring system for lung cancer patients with MSCC after surgery based on survival and functional outcome. The scoring system can guild surgeons to select the individual strategy for patients with MSCC from lung cancer.

Prediction of survival prognosis after surgery in patients with symptomatic metastatic spinal cord compression from non-small cell lung cancer.

BackgroundThe aim of this study was to develop a scoring system for prediction of survival prognosis after surgery in patients with symptomatic metastatic spinal cord compression (MSCC) from non-small cell lung cancer (NSCLC).MethodsWe retrospectively analyzed nine preoperative characteristics for survival in a series of 64 patients with NSCLC who were operated with posterior decompression and spine stabilization for MSCC. Characteristics significantly associated with survival on multivariate analysis were included in the scoring system. The scoring point for each significant characteristic was derived from the hazard ratios on Cox proportional hazards model. The total score for each patient was obtained by adding the scoring points of all significant characteristics.ResultsEastern Cooperative Oncology Group (ECOG) performance status, number of involved vertebrae, visceral metastases, and time developing motor deficits had significant impact on survival on multivariate analysis and were included in the scoring system. According to the prognostic scores, which ranged from 4 to 10 points, three prognostic groups were designed: 4–5 points (n = 22), 6–7 points (n = 23), and 8–10 points (n = 19). The corresponding 6-month survival rates were 95, 47 and 11 %, respectively (P < 0.0001). In addition, the functional outcome was worse in the group of patients with 8–10 points compared with other two prognostic groups.ConclusionsThe new scoring system will enable physicians to identify patient with MSCC from NSCLC who may be a candidate for decompression and spine stabilization, more radical surgery, or supportive care alone. Patients with scores of 4–5, who have the most favorable survival prognosis and functional outcome, can be treated with more radical surgery in order to realize better local control of disease and prevent the occurrence of local disease. Patients with scores of 6–7 points should be surgical candidates, because survival prognosis and functional outcome are acceptable after surgery, while patients with scores of 8–10 points, who have the shortest survival time and poorest functional outcome after surgery, appear to be best treated with radiotherapy or best supportive care.

A validated preoperative score predicting survival and functional outcome in lung cancer patients operated with posterior decompression and stabilization for metastatic spinal cord compression.

This study aims to create and validate a score for survival and functional outcome of lung cancer patients with metastatic spinal cord compression (MSCC) after posterior decompressive surgery. The entire cohort of 73 consecutive patients was randomly assigned to a test group (N=37) and a validation group (N=36). In the test group, we retrospectively analyzed 10 preoperative characteristics. Characteristics significantly associated with survival on multivariate analysis were included in the score. Patients in the validation group were used to confirm whether the score was reproducible. Postoperative functional outcome was analyzed both in the test and validation groups. On multivariate analysis, preoperative ambulatory status (P=0.0017), visceral metastases (P=0.0002), and time developing motor deficits (P=0.0004) had significant impact on survival and were included in the scoring system. According to the prognostic scores, which ranged from 0 to 6 points, two risk groups were designed: 0-2 and 3-6 points and the median survival was 2.6months (95% CI, 1.0-3.8months) and 10.7months (95% CI, 7.1-13.7months), respectively (P<0.0001). In the validation group, the corresponding median survival was 2.7months (95% CI, 1.6-5.5months) and 10.8months (5.8-13.6months), respectively (P<0.0001). In addition, the functional outcome was worse in patients with 0-2 points than in patients with 3-6 points both in the test (P=0.0023) and validation groups (P=0.0298). Patients with scores of 0-2 points, who have short survival time (life expectancyless than 3months) and poor functional outcome, appear best treated with radiotherapy or best supportive care alone. Surgery may be no longer in consideration in most of the patients in this group. Patients with score of 3-6 points should be surgical candidates, because survival prognosis (life expectancy more than 10months) and functional outcome are favorable after surgery.

A new instrument for estimation of survival in elderly patients irradiated for metastatic spinal cord compression from breast cancer.

BackgroundElderly patients become more important in oncology. In this group, personalized treatment approaches taking into account survival prognoses and comorbidities play a major role. Predictive instruments are necessary to estimate the survival of elderly cancer patients. The importance of separate instruments for different tumor entities has been recognized. In this study, an instrument was generated to estimate the survival of elderly patients developing metastatic spinal cord compression (MSCC) from breast cancer.MethodsIn 218 elderly patients (age ≥65 years) irradiated for MSCC from breast cancer, nine factors were evaluated for survival: fractionation regimen, age, time from breast cancer diagnosis to RT of MSCC, visceral metastases, other bone metastases, time developing motor deficits, pre-radiotherapy ambulatory status, number of involved vertebrae, and Eastern Cooperative Oncology Group (ECOG) performance score. Factors significantly associated with survival in the Cox regression analysis were included in the prognostic instrument. Scores for each factor were calculated by dividing the 6-months survival rates by 10. The sums of these scores represented the patients’ scores.ResultsOn multivariate analyses, visceral metastases (p < 0.001), time developing motor deficits (p < 0.001), ambulatory status (p < 0.001), number of involved vertebrae (p = 0.032), and ECOG performance score (p < 0.001) were significant and included in the prognostic instrument. Based on the patients’ scores, three groups were designed: 18–27 points, 28–39 points and 40–42 points. Six-months survival rates were 4, 62 and 100 %, respectively (p < 0.001).ConclusionsThis new instrument contributes to personalized treatment in elderly patients with MSCC from breast cancer by predicting an individual patient’s survival prognosis.

Single-Fraction Versus 5-Fraction Radiation Therapy for Metastatic Epidural Spinal Cord Compression in Patients With Limited Survival Prognoses: Results of a Matched-Pair Analysis

This study compared single-fraction to multi-fraction short-course radiation therapy (RT) for symptomatic metastatic epidural spinal cord compression (MESCC) in patients with limited survival prognosis. A total of 121 patients who received 8 Gy × 1 fraction were matched (1:1) to 121 patients treated with 4 Gy × 5 fractions for 10 factors including age, sex, performance status, primary tumor type, number of involved vertebrae, other bone metastases, visceral metastases, interval between tumor diagnosis and MESCC, pre-RT ambulatory status, and time developing motor deficits prior to RT. Endpoints included in-field repeated RT (reRT) for MESCC, overall survival (OS), and impact of RT on motor function. Univariate analyses were performed with the Kaplan-Meier method and log-rank test for in-field reRT for MESCC and OS and with the ordered-logit model for effect of RT on motor function. Doses of 8 Gy × 1 fraction and 4 Gy × 5 fractions were not significantly different with respect to the need for in-field reRT for MESCC (P=.11) at 6 months (18% vs 9%, respectively) and 12 months (30% vs 22%, respectively). The RT regimen also had no significant impact on OS (P=.65) and post-RT motor function (P=.21). OS rates at 6 and 12 months were 24% and 9%, respectively, after 8 Gy × 1 fraction versus 25% and 13%, respectively, after 4 Gy × 5 fractions. Improvement of motor function was observed in 17% of patients after 8 Gy × 1 fraction and 23% after 4 Gy × 5 fractions, respectively. There were no significant differences with respect to need for in-field reRT for MESCC, OS, and motor function by dose fractionation regimen. Thus, 8 Gy × 1 fraction may be a reasonable option for patients with survival prognosis of a few months.