Elisabetta Perrucci

Radiation therapy in metastatic spinal cord compression. A prospective analysis of 105 consecutive patients

One hundred thirty consecutive patients with metastatic spinal cord compression (MSCC) were entered in a therapeutic protocol in which radiation therapy (RT) played the main role. When MSCC is diagnosed by clinical‐radiologic methods such as myelography with or without computed tomography (CT) or magnetic resonance imaging (MRI), steroids are given and RT treatment started within 24 hours. When diagnostic doubts exist or stabilization is necessary, surgery precedes RT. Chemohormonal potentially responsive tumors are also treated with chemotherapy or hormonal therapy. Twelve patients (9.2%) underwent surgery plus RT, and 118 (90.8%) received RT alone. Thirteen (11%) early death patients were not evaluable. The 105 evaluable cases that received RT alone were analyzed. Median follow‐up was 15 months (range, 4 to 38 months). Response among patients with back pain was 80%. In cases with motor dysfunction, 48.6% improved, and in 33 of 105 patients (31.4%) without motor disability there was no deterioration. Forty percent of patients with autonomic dysfunction responded to RT. Median survival time was 7 months with a 36% probability of survival for 1 year. The median duration of improvement was 8 months. The most important prognostic factor was early diagnosis. Radiosensitivity of tumor was only important in paraparetic patients in predicting response to RT. Complete myelographic block significantly diminished response to RT. Vertebral collapse did not influence response or survival.

Short-course radiotherapy (8 Gy × 2) in metastatic spinal cord compression: An effective and feasible treatment

PURPOSE To evaluate the clinical outcome and toxicity of a short-course regimen of radiotherapy (RT) in selected metastatic spinal cord compression (MSCC) patients. METHODS AND MATERIALS Between 1993 and 1995, 53 consecutive patients with MSCC from low radio-responsive primary tumors (non small cell lung, kidney, head and neck and gastrointestinal carcinomas, melanoma and sarcomas), or more radio-responsive ones (breast and prostate carcinomas, myeloma and lymphomas) with paresis, plegia, low performance status (PS ECOG > or = 2), and/or short life expectation, underwent short-course RT; a single fraction of 8 Gy repeated after 1 week in responders or stable patients, for a total dose of 16 Gy. Of 49 (92%) evaluable cases, 4 (8%) underwent surgery plus RT and the other 45 RT alone. Medium doses of parenteral dexamethasone (8 mg x 2/d) were given in all cases and precautional anti-emetics to those treated with fields covering the upper abdomen (20 of 49 cases). Median follow up was 25 months (range, 6-34). Response was assessed according to back pain, and motor and bladder capacity before and after RT. RESULTS Pain relief was achieved in 67% of patients and motor function response rate reached 63%. Early diagnosis and therapy were very important in predicting response to RT; all but two (91%) pretreatment walking patients and all but one (98%) with good bladder function preserved these capacities. On the contrary, when diagnosis was late, only 38% of nonambulatory patients and 44% of those with bladder retention improved. Median survival was 5 months, with a 30% probability of survival for 1 year. Length of survival was significantly longer for patients able to walk before and/or after RT. Good agreement between survival and duration of response was found with no evidence of relapse in the irradiated spine. Sickness appeared only in a few cases. Slight esophagitis was more frequent: dysphagia for solid foods in one-third of patients irradiated on the thoracic spine. Late toxicity was never recorded. CONCLUSION The short-course RT adopted gave a clinical outcome comparable with that resulting from more protracted regimens with only slight side effects. The use of a few large treatment fractions could be explored considering the associated advantages for patients and radiotherapy centers often overloaded by long patient waiting lists.

Comparison of two Different Radiotherapy Schedules for Spinal Cord Compression in Prostate Cancer

Aims and background To assess the clinical outcome and toxicity of two different radiotherapy (RT) schedules for the management of metastatic spinal cord compression from prostate cancer, we performed a prospective analysis of 44 patients with the complication. Methods Two different RT schedules were adopted, a split-course regimen of 5 Gy x 3, 4 days rest, and then 3 Gy x 5, and a short-course regimen of 8 Gy, 7 days rest, and then 8 Gy. The split-course RT was adopted for all prostate cancer patients referred to our center between 1986 and 1992. Starting in 1993, the short-course RT was added for patients with a poor prognosis (i.e., paresis or paraplegia, low performance status, and/or short life expectation), whereas others still underwent the split-course regimen. So, 27 (61%) patients were treated with the split-course and the other 17 (39%) with the short-course regimen. Medium follow-up was 48 months (range, 6 to 123). Results Back pain total response rate was 82%. Effectiveness of RT on motor and bladder capacity was conditioned by pretreatment status of patients. All 20 (100%) walking cases maintained the function, whereas 11 of 24 (46%) with motor impairment regained the ability. The difference in response rate was statistically significant (P<0.001). All 36 (100%) patients, able to void at presentation preserved the capacity, whereas 3 of 8 (38%) with sphincter dysfunction no longer needed an indwelling catheter. Posttreatment neurologic status was the only factor found to affect survival. Median survival, 9 months for the whole group, was 10 and 2 months for posttreatment walking and nonwalking patients, respectively (10 vs 2 months, P<0.001). Neither presence of other metastases nor RT regimen used (split vs short-course) conditioned response rate, duration of response or survival. Acute or late, severe toxicity was never recorded. No patient complained of spinal cord morbidity. Conclusions Both split-course and short-course RT schedules were effective and without complications. Early diagnosis was the most important prognostic factor, but there was also recovery of function in about half of the patients unable to walk, and about one-third of patients with bladder dysfunction before treatment. Since length of the course of therapy is a factor with an important impact on the patients quality of life, the short-course RT regimen adopted in the trial merits further investigation.

Radiation therapy of spinal cord compression caused by breast cancer: report of a prospective trial

Fifty-six breast cancer patients with metastatic spinal cord compression were consecutively treated with radiation therapy alone. All patients received steroids plus chemotherapy and/or hormonal therapy. Emergency radiation therapy was administered using a split-course regimen: 5 Gy for 3 days, stopped for 4 days and, only in responders, a further 3 Gy for 5 days (time dose fractionation 68). Median follow-up was 22 months (range, 4 to 52 months). Response and survival were assessed on the basis of, pretreatment and posttreatment walking capacity, presence of vertebral body collapse or osteolysis, presence of other metastatic sites apart from bone and chemotherapy and/or hormonal therapy. In 89% of patients with back pain the pain disappeared or lessened. Four of 6 cases (67%) with urinary dysfunction responded to radiation therapy. Of 35 cases with motor dysfunction at the time of diagnosis, 21 (60%) regained the ability to walk and another five (14%) who were able to walk with support at diagnosis did not deteriorate. All 21 cases without motor deficits before treatment maintained good motor performance after radiation therapy. Response to therapy was better in pretreatment walking than in nonwalking patients (97% vs 69%; p less than 0.02). Probability of duration of response at 1 year was 59% and 10% for posttreatment walking and nonwalking patients, respectively (p less than 0.0001). One year survival probability was 66% for posttreatment walking and 10% for posttreatment nonwalking patients, respectively (p less than 0.0001). Pretreatment and posttreatment ambulatory status were the most important prognostic factors.

Lung damage following bone marrow transplantation after hyperfractionated total body irradiation

From July 1985 to December 1989, 72 evaluable patients aged between 6 and 51 (median age 27 years) suffering from haematological malignancies received an allogeneic bone marrow transplant (BMT) depleted of T-lymphocytes to reduce the risk of graft-versus-host-disease (GvHD); 57 were matched and 15 mismatched. Three different conditioning regimens were used in an effort to enhance cytoreduction without increase extramedullary toxicity. Mismatched patients were treated with more immunosuppressive regimens. Total body irradiation (TBI) was given in three doses per day, 5 h apart, over 4 days for a total of 12 fractions. The dose to the lungs was 14.4, 15.6 and 9 Gy according to the conditioning regimen. The incidence of interstitial pneumonia (IP) was 12.3% in matched and 46.7% in mismatched patients. Our results seem to indicate that lung toxicity is correlated with the intensity of the conditioning regimen, the stage of disease and, in mismatched patients, with the degree of human leucocyte antigen (HLA) disparity and the poor post-BMT reconstitution, rather than the radiotherapy dose delivered to the lungs. On the contrary, the hyperfractionated scheme adopted, the absence of GvHD and, perhaps, the post-TBI administration of cyclophosphamide all seem to have contributed to the low incidence of IP in our matched patients.

Interstitial pneumonitis after hyperfractionated total body irradiation in hla-matched t-depleted bone marrow transplantation

Interstitial pneumonia is one of the major causes of morbidity and mortality after bone-marrow transplantation. We here report a series of 58 patients suffering from hematological malignancies who received HLA-matched T-lymphocyte depleted bone-marrow transplants between July 1985 and January 1990. Interstitial pneumonia occurred in 7/58 patients (12%) and was fatal in six. Three different pre-bone-marrow transplantation conditioning regimens were employed. Total body irradiation was delivered according to a hyperfractionated scheme of 12 fractions given three per day 5 hr apart for 4 days. Twenty-three patients received 36 mg/Kg procarbazine, 1275 UL/Kg antithymocite globulin, 14.4 Gy hyperfractionated total body irradiation and 120 mg/Kg cyclophosphamide. Only one patient developed interstitial pneumonia, but two rejected the graft and 10 relapsed. As a consequence, the total hyperfractionated scheme was increased to 15,6 Gy, cyclophosphamide to 200 mg/Kg, antithymocite globulin to 3400 UL/Kg and procarbazine eliminated. There were three cases of interstitial pneumonia, no rejection and four relapses in the 17 patients who received this regimen. In the last 18 patients hyperfractionated total body irradiation was reduced to 15 Gy, cyclophosphamide to 100 mg/Kg, and 10 mg/Kg of the myeloablative agent thiothepa added to enhance the cytoreductive effect without significantly increasing extramedullary toxicity. Three cases of interstitial pneumonia, one relapse but no rejection were recorded. Our results demonstrate that the absence of graft-versus-host disease due to T-cell depletion, and radio-chemotherapy doses and schedules used for the conditioning regimen each contributed to reducing the risk of interstitial pneumonitis. Hyperfractionated total body irradiation therefore, seems to play an important role in lowering the incidence of this complication.

Partial breast irradiation with interstitial high-dose-rate brachytherapy in early breast cancer : Results of a phase II prospective study

AIM To investigate, in a phase II prospective study, the efficacy of partial breast irradiation administered with high-dose-rate brachytherapy. METHODS After conservative surgery 80 patients with low-risk early-stage breast cancer received 4 Gy twice a day for 4 days (total dose 32 Gy). Catheter implantation was performed during surgery in 15 cases and postoperatively, at a median of 8 weeks from surgery, in 65 patients. Adjuvant therapy was chemotherapy (8) and/or hormone therapy (61). RESULTS Cosmetic results were good/excellent in 79 patients. Perioperative toxicity was very low. Acute skin toxicity developed in seven cases (six G1; one G2); late G3 cutaneous toxicity in one patient and late subcutaneous toxicity in five (three G1; two G2). Grade 1 teleangiectasia occurred in eight patients and grade 2 in one. Fat necrosis was symptomatic in one patient and asymptomatic in five. Only one patient presented pain after brachytherapy. A significantly (p=0.001) higher frequency of late toxicity was observed in patients implanted during surgery, the group, which included the only patient with a fair cosmetic result. No local or regional relapses have occurred to date. The median follow-up was 30 months (range 3-52). CONCLUSION This strategy is a viable option in selected patients with early-stage breast cancer as it is feasible, reproducible and associated with very low perioperative and acute toxicity. The low incidence of late side effects will probably change as follow-up lengthens.

Outcome of a phase II prospective study on partial breast irradiation with interstitial multi-catheter high-dose-rate brachytherapy

BACKGROUND AND PURPOSE Partial breast irradiation (PBI) is an alternative to whole-breast irradiation after breast-conserving surgery in selected patients. Until the results of randomized phase III studies are available, phase II studies inform about PBI. We report the 5 year results of a phase II prospective study with PBI using interstitial multi-catheter high-dose-rate brachytherapy (ClinicalTrials.gov Identifier: NCT00499057). METHODS Hundred patients received PBI (4 Gy, twice a day for 4 days, until 32 Gy). Inclusion criteria were: age ≥ 40years, infiltrating carcinoma without lobular histology, ductal in situ carcinoma, tumor size ≤ 2.5 cm, negative surgical margins and axillary lymph nodes. RESULTS At a median follow-up of 60 months late toxicity occurred in 25 patients; the 5-year probability of freedom from late toxicity was 72.6% (95% CI: 63.7-81.7). Tamoxifen was the only significant risk factor for late toxicity. Cosmetic results, judged by physicians and patients, were good/excellent in 98 patients. Three local relapses (1 true, 2 elsewhere) and 1 regional relapse occurred. The 5-year probability of local or regional relapse-free survival was 97.7% (95% CI: 91.1-99.4) and 99.0% (95% CI: 92.9-99.8), respectively. CONCLUSION PBI with interstitial multi-catheter brachytherapy is associated with low relapse and late toxicity rates.

Partial breast irradiation with interstitial multi-catheter high-dose-rate brachytherapy. Long-term results of a phase II prospective study

PURPOSE We report the long-term results of phase II prospective study with accelerated partial breast irradiation (APBI) using interstitial multi-catheter high-dose-rate brachytherapy. METHODS 240 patients received APBI (4Gy, twice daily; total dose 32Gy). RESULTS Median follow-up was 96months. Recurrences in the treated breast developed in 8 patients (3.3%) at a median of 73months after APBI. The 5- and 10-year cumulative incidences were respectively, 1.8% (95%CI: 0.6-4.3) and 6.6% (95%CI: 2.7-12.9). Regional recurrences developed in 5 patients (2%) at a median of 28months and distant metastases in 8 (3.3%) at a median of 32.5months. Breast cancer specific mortality occurred in 6 patients (2.5%) at a median of 60months. Acute toxicity developed in 71 (29.6%) patients (G1 in 60 and G2 in 11). Almost all were skin toxicity and hematomas. Late toxicity was observed in 90 patients (37.5%), G1 in 97 cases and G2 in 11. Some patients presented with more than one type of toxicity. Teleangectasia and fibrosis were the most common (48 and 44 cases respectively), followed by fat necrosis (in 18 patients) Tamoxifen emerged as the only risk factor for breast fibrosis (p=0.007). Cosmetic results were judged by the physicians as excellent in 174 (83.7%) patients, good in 25 (12%) fair in 8 (3.8%) and poor in 1 (0.5%); 174 patients (83.7%) judged outcomes as excellent, 26 (12.4%) as good, 7 (3.4%) as fair and 1 (0.5%) as poor. Physician/patient agreement was good (weighted k-value 0.72). CONCLUSIONS APBI with interstitial multi-catheter brachytherapy was associated with good outcomes, low relapse and toxicity rates. Few events during this long-term follow-up preclude identifying specific features of patients at risk of relapse and illustrate the need for a large data-base.

Recurrences and toxicity after adjuvant vaginal brachytherapy in Stage I–II endometrial cancer: A monoinstitutional experience

PURPOSE To evaluate the incidences of vaginal recurrence and toxicity after vaginal brachytherapy in Stage I-II endometrial cancer. METHODS AND MATERIALS Between 2003 and 2012, 150 high-intermediate-risk Stage I and 7 Stage II patients, median age 64 years, underwent surgery, with or without lymphadenectomy, and 3D brachytherapy: 7 Gy, at 5 mm depth from applicator surface, for 3-week fractions. The effects of age, grading, number of excised lymph nodes and pathologic stage on loco-regional relapse (LRR), metastases, and tumor-related death were investigated. Vaginal toxicity was evaluated during followup visits. RESULTS At 83 months of median followup, 144 patients were disease free, 2 in relapse, 7 deceased from disease, and 4 from other causes. One vaginal (0.6%), five nodal (3.2%), three pelvic over the vaginal cuff (1.9%), and one distant recurrences were seen (0.6%). The 5-year probability of LRR-free, distant metastasis-free and cause-specific survivals for all patients were 93.6% (95% confidence interval [CI]: 88.1-96.7), 97.8% (95% CI: 93.2-99.3), and 96.5% (95% CI: 93.5-99.5) and for Stage I 95.7% (95% CI: 92.2-9.1), 99.3% (95% CI: 98.0-100), and 97.7% (95% CI: 95.2-100), respectively. At multivariate analysis, Stage II disease and more than 12 lymph nodes sampled were associated with LRR (hazard ratio [HR]: 3.88; 95% CI: 1.390-10.878; p = 0.010 and HR: 6.952; 95% CI: 1.591-30.385; p = 0.010) and Stage II with metastasis and tumor-related death (HR: 23.057; 95% CI: 2.296-231.485; p = 0.008 and HR: 4.324; 95% CI: 1.223-15.290; p = 0.023). Vaginal acute and chronic toxicity was 16% and 55.4%, respectively, all only Grades 1-2. CONCLUSIONS For high-to-intermediate-risk Stage I endometrial cancer, 3D vaginal brachytherapy achieved good local control and low toxicity. In Stage II, patients brachytherapy could be administered after complete surgical staging.