Local Failure After Accelerated Partial Breast Irradiation with Intraoperative Radiotherapy with Electrons: An Insight into Management and Outcome from an Italian Multicentric Study.

BACKGROUND: The aim of this work is to evaluate pattern of care and clinical outcome in a large series of patients with in-breast recurrence (IBR), after quadrantectomy and intraoperative radiation therapy with electrons (IOERT) as partial breast irradiation. PATIENTS AND METHODS: Patients with IBR after IOERT, treated with salvage surgery ± adjuvant reirradiation (re-RT), were selected from a multiinstitution database. Disease-free survival (DFS), overall survival (OS), cumulative incidence of second IBR, and distant metastases (DM) were estimated. RESULTS: A total of 224/267 patients from seven institutions were included. Primary tumors received 21 Gy. Median time to first IBR was 4.3 years (range 2.6-6.1 years). Salvage mastectomy and repeat quadrantectomy were performed in 135 (60.3%) and 89 (39.7%) patients, followed by adjuvant re-RT in 21/135 (15.5%) and 63/89 (70.8%), respectively. Median follow-up after salvage treatment was 4.1 years. Overall, 5- and 8-year outcomes were as follows: cumulative incidence of second IBR: 8.4% and 14.8%; cumulative incidence of DM: 17.1% and 22.5%; DFS: 67.4% and 52.5%; OS: 89.3% and 74.7%. The risk of second IBR was similar in the salvage mastectomy and repeat quadrantectomy + RT groups [hazard ratio (HR) 1.41, p = 0.566], while salvage mastectomy patients had greater risk of DM (HR 3.15, p = 0.019), as well as poorer DFS (HR 2.13, p = 0.016) and a trend towards worse OS (HR 3.27, p = 0.059). Patients who underwent repeat quadrantectomy alone had worse outcomes (second IBR, HR 5.63, p = 0.006; DFS, HR 3.21, p = 0.003; OS, HR 4.38, p = 0.044) than those adding re-RT. CONCLUSIONS: Repeat quadrantectomy + RT represents an effective salvage approach and achieved local control comparable to that of salvage mastectomy.

Frequency of brain metastases from prostate cancer: an 18-year single-institution experience.

It has recently been reported that the incidence of brain metastases (BMs) from prostate cancer (PC) has increased in comparison with historical series. The aim of this study was to compare the incidence of BMs in the pre- and post-docetaxel era in a single institution in which all oncological patients are referred to one Radiotherapy and one Medical Oncology Department. We searched the electronic databases of these departments for all males with BMs entered from 1994 to 2011. The year of the introduction of docetaxel into clinical practice (2002) divided the observation period into two 9-year periods: period 1 (P1) from 1994 until 2002 (P1), and period 2 (P2) after 2002. The number of patients with BMs was constant: 241 patients in P1 and 249 in P2. The greatest changes in frequency between P1 and P2 involved colorectal cancer (+75.9 %), renal cancer (+141.9 %), and PC (+238.7 %). The total number of patients with BMs from PC was nine: two in P1 (0.8 %) and seven in P2 (2.8 %). All but two of these patients developed BMs after becoming castration-resistant. Median BM-free survival was 36 months, whereas median BM survival was 8 weeks. As the appearance of BMs in the natural history of PC is usually related to the late phase of the disease, and mortality due to PC remained constant, it seems that there really has been an increase in the frequency of BMs from PC that may reflect a gain in survival.

Impact of residual setup error on parotid gland dose in intensity-modulated radiation therapy with or without planning organ-at-risk margin.

PURPOSE: To estimate the dosimetric impact of residual setup errors on parotid sparing in head-and-neck (H&N) intensity-modulated treatments and to evaluate the effect of employing an PRV (planning organ-at-risk volume) margin for the parotid gland. PATIENTS AND METHODS: Ten patients treated for H&N cancer were considered. A nine-beam intensity-modulated radiotherapy (IMRT) was planned for each patient. A second optimization was performed prescribing dose constraint to the PRV of the parotid gland. Systematic setup errors of 2 mm, 3 mm, and 5 mm were simulated. The dose-volume histograms of the shifted and reference plans were compared with regard to mean parotid gland dose (MPD), normal-tissue complication probability (NTCP), and coverage of the clinical target volume (V95% and equivalent uniform dose [EUD]); the sensitivity of parotid sparing on setup error was evaluated with a probability-based approach. RESULTS: MPD increased by 3.4%/mm and 3.0%/mm for displacements in the craniocaudal and lateral direction and by 0.7%/ mm for displacements in the anterior-posterior direction. The probability to irradiate the parotid with a mean dose > 30 Gy was > 50%, for setup errors in cranial and lateral direction and < 10% in the anterior-posterior direction. The addition of a PRV margin improved parotid sparing, with a relative reduction in NTCP of 14%. The PRV margin compensates for setup errors of 3 mm and 5 mm (MPD < or = 30 Gy in 87% and 60% of cases), without affecting clinical target volume coverage (V95% and EUD variations < 1% and < 1 Gy). CONCLUSION: The parotid gland is more sensitive to craniocaudal and lateral displacements. A setup error of 2 mm guarantees an MPD < or = 30 Gy in most cases, without adding a PRV margin. If greater displacements are expected/accepted, an adequate PRV margin could be used to meet the clinical parotid gland constraint of 30 Gy, without affecting target volume coverage.

Surgery and radiotherapy in the treatment of malignant parotid tumors: a retrospective multicenter study.

AIMS AND BACKGROUND: Major salivary gland cancers are rare, with many histologic types and subtypes. The low incidence and heterogeneity of primary parotid carcinomas makes their outcome difficult to evaluate. Treatment remains primarily surgical, but optimal therapeutic regimens have yet to be fully realized. The present study reviews the experience of three Italian institutions in the treatment of primary parotid carcinomas in order to describe the clinicopathological presentation and treatment options with emphasis on radiotherapy and to analyze the factors influencing survival. METHODS AND STUDY DESIGN: The records of 110 patients with primary parotid neoplastic lesions treated at three Italian institutions from 1993 to 2004 were retrospectively reviewed. Six patients were excluded from the study: 3 received surgery alone and 3 were not assessable, for a total of 104 assessable patients. Acute and late toxicity of radiotherapy was quantified following the recommendations of the RTOG/EORTC. Survival was analyzed by the actuarial Kaplan-Meier product-limit method. The influence of selected factors on 10-year disease-specific survival was analyzed. RESULTS: The 104 assessable patients were treated as follows: 11 patients received radiotherapy as their only treatment (3 with a palliative purpose) and 93 had postoperative radiotherapy. Thirty-two patients underwent neck dissection: neck lymph node metastases were found in all them. Their mean age was 60 years (range, 14-92). According to the UICC/2002 TNM Classification, 8 patients were stage I, 19 stage II, 34 stage III, 25 stage IVA, 5 stage IVB, 3 recurrent and 10 not assessable (Tx). The most frequent histologies were adenoid cystic carcinoma (n = 16), mucoepidermoid carcinoma (n = 15), and acinic cell carcinoma (n = 15). Twenty-three patients had recurrences: 10 had local recurrences, 3 neck recurrences, 9 distant metastases, and 1 patient had both local recurrence and distant metastases. No factors were observed that would negatively influence the prognosis. Actuarial 10-year disease-specific survival was 71% and actuarial 10-year local control 82%. CONCLUSIONS: The treatment of salivary gland malignancies remains primarily surgical. Our study confirms the results of the literature with surgery and adjunctive radiotherapy in patients with advanced-stage disease. No variables were observed to influence the prognosis.

Policies for reirradiation of recurrent high-grade gliomas: a survey among Italian radiation oncologists.

PURPOSE: To assess the contribution of Italian radiation oncologists in the current management of recurrent high-grade gliomas (HGG), focusing on a reirradiation (reRT) approach. METHODS: In 2015, the Reirradiation and the Central Nervous System Study Groups on behalf of the Italian Association of Radiation Oncology (AIRO) proposed a survey. All Italian radiation oncologists were individually invited to complete an online questionnaire regarding their clinical management of recurrent HGG, focusing on a reRT approach. RESULTS: A total of 37 of 210 questionnaires were returned (18% of all centers): 16 (43%) from nonacademic hospitals, 14 (38%) from academic hospitals, 5 (13%) from private institutions, and 2 (6%) from hadron therapy centers. The majority of responding centers (59%) treated ≤5 cases per year. Performance status at the time of recurrence, along with a target diameter <5 cm and an interval from primary radiation ≥6 months, were the prevalent predictive factors considered for reRT. Sixty percent of reirradiated patients had already received a salvage therapy, either chemotherapy (40%) or reoperation (20%). The most common approach for reRT was fractionated stereotactic radiotherapy to a mean (photon) dose of 41.6 Gy. CONCLUSIONS: Although there were wide variations in the clinical practice of reRT across the 37 centers, the core activities were reasonably consistent. These findings provide a basis for encouraging a national collaborative study to develop, implement, and monitor the use of reRT in this challenging clinical setting.

Prospective evaluation of quality of life after interstitial brachytherapy for localized prostate cancer.

PURPOSE: Permanent interstitial brachytherapy (IB) has become an increasingly appealing therapeutic option for localized prostate cancer (LPC) among physicians and patients because it involves short hospitalization and treatment and its postulated low degree of toxicity may reduce its impact on the patients' quality of life (QoL). The aim of this prospective study was to assess the impact of IB on the QoL of patients with LPC. METHODS AND MATERIALS: A validated self-completed questionnaire was administered to the patients before and after IB and then at yearly intervals. The items allowed the identification of seven subscales exploring physical well-being (PHY), physical autonomy (POW), psychological well-being (PSY), relational life (REL), urinary function (URI), rectal function (REC), and sexual function (SEX). RESULTS: The assessment of the QoL of 147 patients treated between May 2000 and February 2005 revealed no relevant differences in the PHY scale scores 1 month after IB or later, and the same was true of the POW, PSY, and REL scales. Urinary function significantly worsened after IB and returned to pretreatment levels only after 3 years; the impact of the treatment on the URI scale was greater in the patients with good baseline urinary function than in those presenting more urinary symptoms before IB. Rectal and sexual functions were significantly worse only at the post-IB evaluation. CONCLUSIONS: The results of the present study confirm that the impact of IB on the patients' QoL is low despite its transient negative effects on some function, and extend existing knowledge concerning QoL after IB.

Impact of post-implant dosimetric parameters on the quality of life of patients treated with low-dose rate brachytherapy for localised prostate cancer: results of a single-institution study.

BACKGROUND: To assess the relationship between dosimetric parameters and the quality of life (QL) outcomes of patients with low-intermediate-risk localised prostate cancer (LPC) treated with low-dose-rate brachytherapy (LDR-BT). MATERIALS AND METHODS: We evaluated the participants in two consecutive prospective studies of the QL of patients treated with LDR-BT for LPC. QL was evaluated by means of a patient-completed questionnaire assessing non functional [physical (PHY) and psychological (PSY) well-being, physical autonomy (POW), social relationships (REL)] and functional scales [urinary (URI), rectal (REC), and sexual (SEX) function]; a scale for erectile function (ERE) was included in the second study. Urethra (D10 ≤ 210 Gy) and rectal wall constraints (V100 ≤ 0.5 cc) were used for pre-planning dosimetry and were assessed with post planning computerized tomography one month later for each patient. RESULTS: QL was assessed in 251 LPC patients. Dosimetry did not influence the non-functional scales. As expected, a progressive impairment in sexual and erectile function was reported one month after LDR-BT, and became statistically significant after the third year. Rectal function significantly worsened after LDR-BT, but the differences progressively decreased after the 1-year assessment. Overall urinary function significantly worsened immediately after LDR-BT and then gradually improved over the next three years. Better outcomes were reported for V100 rectal wall volumes of ≤ 0.5 cc and D10 urethra values of ≤ 210 Gy. CONCLUSIONS: The findings of this study show that dosimetric parameters influence only functional QL outcomes while non-functional outcomes are only marginally influenced.

Phase I study of gemcitabine and radiotherapy plus cisplatin after transurethral resection as conservative treatment for infiltrating bladder cancer.

PURPOSE: Although the use of radical transurethral resection followed by concurrent radiochemotherapy leads to a similar survival rate to that achieved after cystectomy, the number of long-term survivors is low in both cases. An improvement may be obtained by adding a new drug, such as gemcitabine, which is active in bladder cancer and acts as a radiosensitizer. However, because gemcitabine may be very toxic when associated with radiotherapy, we designed this dose-finding study in an attempt to find the dose that can be safely added to radiotherapy and concurrent cisplatin in patients treated with transurethral resection for infiltrating bladder cancer. PATIENTS AND METHODS: After undergoing macroscopically complete transurethral resections for transitional carcinoma of the bladder, patients staged pT2 or higher and without distant metastases concurrently received 54 Gy of fractionated radiotherapy over 6 weeks with cisplatin (100 mg/m(2) q.3 w), starting on Day 1 of radiotherapy. Concomitant gemcitabine was administered on Days 1, 8, and 15 q.3 w for 2 cycles at a dose of 200 mg/m(2), escalated to 500 mg/m(2), with a 100 mg/m(2) increase at each dose level. The maximum tolerated dose was defined as the dose of gemcitabine associated with dose-limiting toxic effects (febrile neutropenia, Grade 4 thrombocytopenia, Grade 3 or 4 enteric toxicity, or Grade 4 nonhematologic toxicity) in 33% of the patients treated at that dose level. Six to 8 weeks after completing the therapy, the patients underwent cystoscopic reevaluation with multiple biopsies of the initial tumor site. RESULTS: Of our consecutive series of 16 patients, 5 received a gemcitabine dose of 200 mg/m(2)/week, 3 a dose of 300 mg/m(2)/week, 3 a dose of 400 mg/m(2)/week, and 5 a dose of 500 mg/m(2)/week for 6 weeks. No dose-limiting toxicity was observed at doses of up to 400 mg/m(2)/week. At the dose 500 mg/m(2)/week, 1 patient experienced an intestinal perforation that recovered after surgery, and another suddenly died after developing Grade 3 untreated diarrhea in the last treatment week. All of the 15 evaluable patients were microscopically disease free at the cystoscopic reevaluation; furthermore, the posttreatment computed tomography scans did not reveal any distant metastases. CONCLUSIONS: After transurethral resection for the conservative treatment of infiltrating bladder cancer, gemcitabine doses of up to 400 mg/m(2)/week seem to be safe in combination with cisplatin and radiotherapy in organ-sparing management. On the basis of the promising results of this Phase I study, we are currently conducting a Phase II trial to verify the possible improvement in local control resulting from the addition of gemcitabine.

The role of brachytherapy in the management of oropharyngeal carcinomas: the Trento experience.

AIMS: This study was undertaken to determine the outcome of patients with oropharyngeal cancer treated at the Radiotherapy Department of the Santa Chiara Hospital (Trento, Italy) with brachytherapy alone or combined with external beam radiotherapy (EBRT). MATERIAL AND METHODS: We retrospectively reviewed the medical records of 87 patients with squamous cell carcinoma of the oropharynx treated by radiation therapy between January 1986 and September 1999. The median age was 59 years and all patients had a minimum follow-up of one year. Tumor locations were 46 tonsillar region, 31 soft palate and 10 base of the tongue. The patients were staged as follows: 41 T1, 35 T2, 11 T3 with 70 N0, 9 N1 and 8 N2. They received either brachytherapy alone (14 patients) or a combination of external beam irradiation and brachytherapy (73 patients) using an afterloading iridium technique in a plastic tube. RESULTS: Overall primary tumor control, including salvage surgery, was 81/87 (93%). Control of metastatic cervical adenopathy was as follows: clinical stage N1, 5/9 patients; N2, 2/8 patients. The estimated five-year cause-specific survival and overall survival rates were 81% and 47%, respectively. After interstitial irradiation severe complications were limited to one case of osteoradionecrosis of the mandible and seven cases of mucosal ulcer. CONCLUSION: This study confirms that iridium-192 interstitial implant alone or as a boost after external beam irradiation is a safe and effective therapy in the management of oropharyngeal carcinomas.

Gemcitabine and radiotherapy plus cisplatin after transurethral resection as conservative treatment for infiltrating bladder cancer: Long-term cumulative results of 2 prospective single-institution studies.

BACKGROUND: Cystectomy is the standard treatment for patients with infiltrating bladder cancer, but conservative treatment with cystoscopic resection followed by radiochemotherapy may be an alternative for highly selected patients. The addition of gemcitabine to cisplatin and radiotherapy may enhance disease control. METHODS: The long-term clinical outcomes of 26 patients enrolled in a previously published dose-finding study and a prematurely discontinued phase 2 trial were evaluated. All the patients underwent transurethral tumor resection followed by a radical dose of external radiotherapy administered at the same time as cisplatin and weekly gemcitabine therapy. RESULTS: After a median follow-up of 74 months, the projected 5-year clinical outcomes were a 70.1% overall survival rate, a 78.9% disease-specific survival rate, and a 73.8% bladder-intact survival rate. CONCLUSIONS: The long-term follow-up data from the current study confirmed that the addition of gemcitabine to radiotherapy and cisplatin is safe and leads to good local and distant disease control. The concomitant administration of cisplatin may explain the good long-term organ preservation that was observed. Conducting confirmatory and comparative trials could satisfy an unmet need but requires the multidisciplinary cooperation of urologists in selecting the right patients for a bladder-sparing strategy.

Full-dose intraoperative radiotherapy with electrons in breast cancer. First report on late toxicity and cosmetic results from a single-institution experience.

PURPOSE: To investigate the feasibility of applying exclusive intraoperative radiation therapy (IORT) after conservative surgery in limited-stage breast carcinoma and to evaluate late effects and cosmetic results after this new conservative treatment. PATIENTS AND METHODS: From October 2000 to November 2002, 47 consecutive patients with unifocal breast carcinoma up to a diameter of 2 cm received conservative surgery followed by IORT with electrons as the sole adjuvant local therapy. Three different dose levels were used: 20 Gy (seven patients), 22 Gy (20 patients), and 24 Gy (20 patients). Patients were evaluated using RTOG/EORTC scale to assess the incidence of late complications. During follow-up, a radiologic assessment with mammography and sonography was periodically performed and any breast-imaging alterations were reported. RESULTS: After a follow-up ranging from 36 to 63 months (median, 48 months), 15 patients developed breast fibrosis (grade 2 in 14 patients, grade 3 in one patient), two patients presented with grade 3 skin changes, one patient developed a clinically relevant fat necrosis, and one patient showed breast edema and pain. Two patients developed contralateral breast cancer and one distant metastases; no local relapses occurred. Asymptomatic findings of fat necrosis were observed at mammography in twelve patients (25.5%), while an hypoechoic area was revealed by sonography in ten patients (21.5%). In four patients (8%), mammographic and sonographic findings suggested malignant lesions and required a rebiopsy to confirm the benign nature of the lesion. CONCLUSION: IORT in breast carcinoma is still an experimental treatment option for select patients with breast cancer and its application should be restricted to prospective trials. Although preliminary data on local control are encouraging, a longer follow-up is needed to confirm the efficacy of IORT in breast cancer and to exclude that severe late complications compromise the cosmetic results or modify the radiologic breast appearance during follow-up increasing the need for additional investigations.

Physical side effects and quality of life during postoperative radiotherapy for uterine cancer. Prospective evaluation by a diary card.

OBJECTIVE: Adjuvant pelvic radiotherapy (XRT) after radical surgery for uterine cancer may cause various (mainly gastrointestinal) side effects capable of affecting a patient's lifestyle. This prospective study used a diary card to evaluate toxicity and daily quality of life changes in uterine cancer patients given postoperative pelvic radiotherapy. METHODS: The self-completed diary card listed 12 items concerning lifestyle changes and side effects. The patients were stratified by age (65 years). RESULTS: Twenty-five patients were evaluable, and a total of 848 days were assessed (82.6% of the 1027 days of XRT). The mean number of daily stools progressively increased during treatment (P < 0.01). No statistically significant differences were observed in terms of nausea or pain. There was a significant decrease in appetite (P < 0.01). Vaginal symptom scores did not significantly change during treatment, and no significant differences were found in terms of anxiety, daily activities, or compliance to therapy. The subjective perception of overall well-being and the quality of life score progressively and significantly decreased over time (P < 0.01). The younger patients had significantly more bowel movements, less appetite, more pain and vaginal burning, less vaginal bleeding, more anxiety, a greater reduction in daily activities and therapeutic compliance, a poorer subjective perception of overall well-being, and a lower quality of life score. CONCLUSIONS: The use of a diary card may be an adequate means of detecting the extent of treatment-related changes in the lifestyle of uterine cancer patients receiving postoperative radiotherapy.

Evaluation of toxicity and quality of life using a diary card during postoperative radiotherapy for rectal cancer.

PURPOSE: Adjuvant pelvic radiotherapy after radical surgery for rectal cancer may produce several side-effects (mainly gastrointestinal) capable of affecting patient lifestyle. This prospective study evaluated by means of a diary card the toxicity and daily changes in the quality of life of patients with rectal cancer treated with postoperative pelvic radiotherapy. METHODS: We used a diary card listing ten items about lifestyle changes and side-effects compiled by patients themselves. The patients were stratified by age (< or = 65 vs. > 65 years), the presence or not of a stoma, and the administration or not of concurrent chemotherapy. RESULTS: Twenty-seven patients were evaluable. The mean number of bowel movements increased across time, without statistically significant differences. Nausea and appetite did not significantly change during the treatment period. There was a statistically significant, progressive increase in the perception of pain (P < 0.03). Although not significantly, the anxiety scores were lower during radiotherapy than at baseline. Daily activities and compliance with therapy did not significantly change during the treatment. There was a significant worsening in overall well-being (P < 0.04) and quality of life evaluation (P < 0.03). The patients who received chemoradiotherapy experienced a worsened lifestyle and greater side-effects. Older patients experienced less pain but had statistically significant higher levels of anxiety. Patients with a stoma reported a better quality of life score than those without. CONCLUSIONS: The use of a diary card may be an adequate means of detecting the extent of treatment-related changes in the lifestyle of patients with rectal cancer treated by postoperative radiotherapy.

Randomized phase III trial of neoadjuvant chemotherapy in head and neck cancer: 10-year follow-up.

In 1986, we initiated a multicenter, randomized trial to compare induction chemotherapy with cisplatin and 5-fluorouracil followed by locoregional treatment (surgery and radiotherapy or radiotherapy alone) with locoregional treatment alone in patients with head and neck squamous cell carcinoma. Here we report the long-term results of the trial. A total of 237 patients with nonmetastatic stage III or IV head and neck carcinoma were randomly assigned to receive four cycles of neoadjuvant chemotherapy followed by locoregional treatment (group A) or locoregional treatment alone (group B). Among all patients, overall survival at 5 and 10 years was 23% (95% confidence interval [CI] = 15.3% to 30.9%) and 19% (95% CI = 11.6% to 26.4%), respectively, for those in group A and 16% (95% CI = 9.6% to 23.4%) and 9% (95% CI = 3.5% to 14.7%), respectively, for those in group B (P = .13). Among operable patients, we observed no difference between group A and group B in overall survival at 5 and 10 years (group A, 31% [95% CI = 14.9% to 47.3%] and 22.7% [95% CI = 7.1% to 38.3%], respectively; group B, 43.3% [95% CI = 25.6% to 61.0%] and 14.2% [95% CI = 0.1% to 28.3%], respectively; P = .73). Among inoperable patients, overall survival at 5 and 10 years was 21% (95% CI = 12.3% to 30.1%) and 16% (95% CI = 7.7% to 23.9%), respectively, for group A and 8% (95% CI = 1.5% to 12.3%) and 6% (95% CI = 0.1% to 9.1%), respectively, for group B (log-rank P = .04). Four cycles of neoadjuvant chemotherapy is a promising approach for treating patients with inoperable advanced head and neck cancer but not for treating patients with operable disease.