Results of a phase II study of Short-course Accelerated Radiation Therapy (SHARON) for multiple brain metastases.

OBJECTIVES: To assess the effectiveness of a SHort-course Accelerated RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. MATERIALS AND METHODS: A phase II clinical trial was designed. Eligibility criteria included patients with at least 3 brain metastases or metastatic disease in >3 organ systems, and Eastern Cooperative Oncology Group performance status of ≤3. Fifty patients were treated with whole brain radiotherapy at 18 Gy (4.5 Gy per fraction) in 2 days with a twice daily fractionation. The primary endpoint was the assessment of efficacy in terms of overall survival. RESULTS: Characteristics of the 50 enrolled patients were: male/female: 24/26; median age: 65 years (range, 45 to 80 y). Eastern Cooperative Oncology Group performance status was <3 in 42 patients (84%). Nineteen patients (38%) were considered to have recursive partitioning analysis class 3 disease. Grade 1-2 acute neurological (46%) and skin (24%) toxicities were recorded. Three patients (6%) experienced neurological grade 3 acute toxicity. With a median follow-up time of 6 months (range, 1 to 18 mo) 2 skin grade 1 late toxicities has been observed. Seventeen of 27 symptomatic patients showed an improvement or resolution of baseline symptoms (overall palliative response rate: 63.0%; 95% confidence interval, 36.6%-82.4%).Two-month overall survival was 86% (median survival time=7 mo). CONCLUSIONS: Short-course accelerated whole brain radiotherapy of 18 Gy in twice daily fractions for 2 consecutive days is tolerated and effective in terms of symptom relief and median survival time. These results justify a phase III comparison against the standard-of-care in this patient population (30 Gy in 10 fractions).

Radioprotective effect of calcium channel blockers against late rectal bleeding in prostate cancer.

OBJECTIVE: This study was done to assess the impact of clinical factors and in particular the use of drugs for concomitant illnesses on late radiation-induced rectal bleeding in patients with prostate cancer. MATERIALS AND METHODS: Patients with histologically proven prostate adenocarcinoma treated with radical radiotherapy and followed up for at least 6 months were selected. The correlation between late rectal bleeding and a number of factors was investigated by univariate and multivariate analysis. RESULTS: A total of 278 patients who underwent radiotherapy at our institution between October 2002 and May 2011 were selected. At univariate analysis, delivery of radiation doses higher than 70 Gy and use of angiotensin-converting enzyme inhibitors were associated with a higher incidence of rectal bleeding. Conversely, patients who used calcium channel blockers had a lower risk (3-year rectal bleeding-free survival 89.8 versus 66.5 %, p = 0.043). At multivariate analysis, use of calcium channel blockers was found to have a protective effect with a hazard ratio of 0.3 (95 % CI 0.12-0.96). Delivery of higher radiation doses was associated with an increased risk of rectal bleeding (hazard ratio 3.02, 95 % CI 1.23-7.38). CONCLUSIONS: Use of calcium channel blockers during and after radiotherapy treatment might have a protective effect against late rectal bleeding. If these results are reconfirmed by larger clinical series, calcium channel blockers may be tested as radioprotector agents in clinical trials.

Extracranial radiosurgery with volumetric modulated arc therapy: Feasibility evaluation of a phase I trial.

The aim of this study was to report early clinical experience in stereotactic body radiosurgery (SBRS) delivered using volumetric intensity modulated arc therapy (VMAT) in patients with primary or metastatic tumors in various extra-cranial body sites. Each enrolled subject was included in a different phase I study arm, depending on the tumor site and the disease stage (lung, liver, bone, metastatic), and sequentially assigned to a particular dose level. Technical feasibility and dosimetric results were investigated. The acute toxicity, tumor response and early local control were also studied. In total, 25 lesions in 20 consecutive patients (male/female, 11/9; median age, 67 years; age range, 47-86 years) were treated. Of these 25 lesions, 4 were primary or metastatic lung tumors, 6 were liver metastases, 8 were bone metastases and 7 were nodal metastases. The dose-volume constraints for organs at risk (OARs) were observed in 19 patients using a single-arc technique. Only in one patient were two arcs required. The treatment was performed without interruption or any other technical issues. The prescribed dose ranged from 12-26 Gy to the planning target volume (PTV). Delivery time ranged from 4 min to 9 min and 13 sec (median, 6 min and 6 sec). No incidence of grade 2-4 acute toxicity was recorded. The overall response rate was 48% (95% confidence interval (CI), 24.2-70.2) based on computed tomography (CT)/magnetic resonance imaging (MRI) and 89% (95% CI, 58.6-98.7) based on the positron emission tomography (PET) scan. SBRS delivered by means of VMAT allowed the required target coverage to be achieved while remaining within the normal tissue dose-volume constraints in the 20 consecutive patients. VMAT-SBRS resulted in adequate technical feasibility; the maximum tolerable dose has not yet been reached in any study arm.

Incidence and management of noncancer pain in cancer patients referred to a radiotherapy center.

OBJECTIVES: The incidence of noncancer pain (NCP) in cancer patients is unknown. An analysis of incidence, severity, impact on quality of life (QoL), and appropriateness of NCP treatment in a cohort of cancer patients referred to a radiotherapy center is reported. MATERIALS AND METHODS: Pain was scored from 0 (absence) to 3 (severe) and the adequacy of analgesic therapy was evaluated according to International Guidelines. Correlation between Pain Management Index and World Health Organization Analgesic Ladder was used to analyze the appropriateness of NCP treatment. In addition, pain was differentiated according to its origin and types and a comparison was performed between cancer pain (CP) and NCP. RESULTS: A total of 903 patients were eligible and 865 (95.8%) were considered evaluable. Three hundred ninety-eight patients (46.0%) had pain. CP and NCP pain incidence was 11.2% and 34.8%, respectively. Pain intensity was higher in patients with CP versus NCP (P=0.021). A neuropathic pain lower incidence (P=0.024) in NCP versus CP was recorded. Moreover, NCP was more inadequately treated than CP (P<0.001). QoL was significantly lower in patients with NCP when compared with patients without pain (P<0.001). In addition, QoL of patients with CP was significantly lower than QoL of patients with NCP (P<0.001). DISCUSSION: In a cancer patients' population referred to a radiotherapy center, the NCP incidence was higher than the CP incidence and NCP intensity was only slightly lower than CP. NCP was significantly pharmacologically undertreated and it was related to a decline in QoL.

Postoperative intensity-modulated radiotherapy with simultaneous integrated boost in prostate cancer: a dose-escalation trial.

OBJECTIVES: To determine the recommended phase II dose of postoperative accelerated intensity modulated radiotherapy (IMRT) for prostate cancer. MATERIAL AND METHODS: Step and shoot IMRT with simultaneous integrated boost (SIB) was delivered in 25 fractions over 5 weeks to patients with high risk resected prostate adenocarcinoma (stage pT3-4 and/or positive surgical margins). Pelvic nodes received 45 Gy at 1.8 Gy/fraction; dose escalation was performed only to the prostate bed (planned dose escalation: 56.8 Gy at 2.27 Gy/fraction, 59.7 Gy at 2.39 Gy/fraction, 61.25 Gy at 2.45 Gy/fraction, 62.5 Gy at 2.5 Gy/fraction). Dose-limiting toxicity (DLT) was any grade ≥ 3 acute toxicity (RTOG score). RESULTS: Twenty-five patients were treated: 7 patients at the 56.75 Gy dose level, 6 patients at each subsequent dose level. Pathologic stages were: pT2c: 2; pT3a: 11; pT3b: 12; pN0: 22; pN1: 3; R0: 7; R1: 18. Median follow-up time was 19 months (range: 6-36 months). No patient experienced DLT. Grade 1-2 acute rectal and urologic toxicity was common (17 and 22 patients, respectively). CONCLUSIONS: The recommended dose was 62.5 Gy in 2.5 Gy/fraction. Postoperative hypofractionated IMRT SIB for prostate cancer seemed to be well tolerated and could be tested in phase II studies.

Daily on-line set-up correction in 3D-conformal radiotherapy: is it feasible?

AIMS AND BACKGROUND: The aim of this report was to investigate the feasibility in terms of treatment time prolongation of an on-line no-action level correction protocol, based on daily electronic portal image verification. METHODS AND STUDY DESIGN: The occupation of a linear accelerator (LINAC) delivering 3-D conformal treatments was monitored for two weeks (from Monday to Friday, 10 working days). An electronic portal image device I-View (Elekta, UK) was used for setup verification. Single-exposure portal images were acquired daily using the initial 8 monitor units delivered for each treatment field. Translational deviations of isocenter position larger than 5 mm or 7 mm, for radical or palliative treatments, respectively, were immediately corrected. In order to estimate the extra workload involved with the on-line protocol, the time required for isocenter check and table correction was specifically monitored. RESULTS: Forty-eight patients were treated. In all, 482 fractions had electronic portal images taken. Two hundred and forty-five setup corrections were made (50.8% of all fractions). The occupation of the LINAC lasted 106 h on the whole. Twelve h and 25 min (11.7% of LINAC occupation time) were spent for portal image verification and setup correction. On the average, 4.3 fractions per hour were carried out. CONCLUSIONS: When used by trained therapists, ideally, portal imaging may be carried out before each fraction, requiring approximately 10% of LINAC occupation time.

A phase I study of short-course accelerated whole brain radiation therapy for multiple brain metastases.

PURPOSE: To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. METHODS AND MATERIALS: A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class>or=2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status≤3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity≥grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded. RESULTS: Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%). CONCLUSIONS: Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices.

Clinical target volume delineation including elective nodal irradiation in preoperative and definitive radiotherapy of pancreatic cancer.

BACKGROUND: Radiotherapy (RT) is widely used in the treatment of pancreatic cancer. Currently, recommendation has been given for the delineation of the clinical target volume (CTV) in adjuvant RT. Based on recently reviewed pathologic data, the aim of this study is to propose criteria for the CTV definition and delineation including elective nodal irradiation (ENI) in the preoperative and definitive treatment of pancreatic cancer. METHODS: The anatomical structures of interest, as well as the abdominal vasculature were identified on intravenous contrast-enhanced CT scans of two different patients with pancreatic cancer of the head and the body. To delineate the lymph node area, a margin of 10 mm was added to the arteries. RESULTS: We proposed a set of guidelines for elective treatment of high-risk nodal areas and CTV delineation. Reference CT images were provided. CONCLUSIONS: The proposed guidelines could be used for preoperative or definitive RT for carcinoma of the head and body of the pancreas. Further clinical investigations are needed to validate the defined CTVs.

Early radiation-induced mucosal changes evaluated by proctoscopy: predictive role of dosimetric parameters.

BACKGROUND AND PURPOSE: Late rectal complications are assessed according to different scoring systems. Endoscopy can provide a more sensitive estimation of early radiation damage. The aim of this paper is to investigate the correlation between dosimetric parameters and rectal mucosal changes after radiotherapy (RT). MATERIALS AND METHODS: Patients with prostate adenocarcinoma treated with curative or adjuvant RT underwent endoscopy 1 year after RT. Receiver operating characteristics (ROC) analysis was performed to analyze the predictive capability of the dosimetric variables in determining mucosal changes classified by Vienna Rectoscopy Score (VRS). RESULTS: The best dosimetric predictors of grade ≥2 telangiectasia were rectal (r) V(60 Gy) (p=0.014), rV(70 Gy) (p=0.017) and rD(mean) (p=0.018). Similar results were obtained for grade ≥2 VRS. The set of rV(60 Gy)<34.4%, rV(70 Gy)<16.7% and rD(mean)<57.5 Gy was associated with a decreased risk of grade ≥2 telangiectasia and VRS. CONCLUSIONS: rV(60 Gy), rV(70 Gy) and rD(mean) were the strongest predictors of rectal mucosal alterations. In-depth analysis is required to correlate each mucosal alteration with late rectal toxicity in order to suggest early proctoscopy as surrogate end-point for rectal late toxicity in studies aimed at reducing this important complication.

Short-course accelerated radiotherapy in palliative treatment of advanced pelvic malignancies: a phase I study.

PURPOSE: To define the maximum tolerated dose of a conformal short-course accelerated radiotherapy in patients with symptomatic advanced pelvic cancer. METHODS AND MATERIALS: A phase I trial in 3 dose-escalation steps was designed: 14 Gy (3.5-Gy fractions), 16 Gy (4-Gy fractions), and 18 Gy (4.5-Gy fractions). The eligibility criteria included locally advanced and/or metastatic pelvic cancer and Eastern Cooperative Oncology Group performance status of ≤ 3. Treatment was delivered in 2 days with twice-daily fractionation and at least an 8-hour interval. Patients were treated in cohorts of 6-12 to define the maximum tolerated dose. The dose-limiting toxicity was defined as any acute toxicity of grade 3 or greater, using the Radiation Therapy Oncology Group scale. Pain was recorded using a visual analog scale. The effect on quality of life was evaluated according to Cancer Linear Analog Scale (CLAS). RESULTS: Of the 27 enrolled patients, 11 were male and 16 were female, with a median age of 72 years (range 47-86). The primary tumor sites were gynecologic (48%), colorectal (33.5%), and genitourinary (18.5%). The most frequent baseline symptoms were bleeding (48%) and pain (33%). Only grade 1-2 acute toxicities were recorded. No patients experienced dose-limiting toxicity. With a median follow-up time of 6 months (range 3-28), no late toxicities were observed. The overall (complete plus partial) symptom remission was 88.9% (95% confidence interval 66.0%-97.8%). Five patients (41.7%) had complete pain relief, and six (50%) showed >30% visual analog scale reduction. The overall response rate for pain was 91.67% (95% confidence interval 52.4%-99.9%). CONCLUSIONS: Conformal short course radiotherapy in twice-daily fractions for 2 consecutive days was well tolerated up to a total dose of 18 Gy. A phase II study is ongoing to confirm the efficacy on symptom control and quality of life indexes.

Concomitant boost plus large-field preoperative chemoradiation in locally advanced uterine cervix carcinoma: Phase II clinical trial final results (LARA-CC-1).

OBJECTIVE: To report the Phase II study final results in terms of pathological complete response (pCR) and complications in locally advanced cervical carcinoma (LACC) patients treated with chemoradiation (CT/RT) regimen based on accelerated fractionation, nodal extended fields and adjuvant radical surgery. METHODS: The sample size was quantified according to published data which shows that CT/RT followed by radical surgery in LACC patients provides a pCR rate above 45%. The 2-stage design by Simon was used to test the null hypothesis that the true pCR would improve by above 20%. The chemoradiation regimen was considered active if >24/43 pCRs were recorded. 40 Gy/2 Gy fraction in 4 weeks was delivered to nodal volume extending up to L3 vertebra, concurrently with chemotherapy. 45 Gy in 20 fractions with a concomitant boost strategy was delivered to the macroscopic disease only. RESULTS: 47 patients were enrolled. Median follow-up was 26 months (3-52 months). Pathological response was assessed in 44/47 patients: 17/44 (38.6%) showed a pCR to treatment, and 9/44 cases (20.5%) showed microscopic disease. Pelvic nodal metastases were documented in 9/44 cases (20.5%). 87.5% of recurrences were extra pelvic. Five patients (11%) developed acute severe gastrointestinal toxicity. The actuarial cumulative 2-year incidence of G ≥ 2 late cutaneous, gastrointestinal, and genitourinary toxicity was 10.3%, 8.3% and 24.9%, respectively. The 3-year DFS was 77.1%, while the 3-year OS was 80.5%. CONCLUSIONS: Our results confirm the high tolerability and efficacy of this accelerated regimen. However, based on the study design, 45 Gy as a concomitant boost CT/RT delivered by a 3D technique does not seem sufficient to increase pCR rate.

Early proctoscopy is a surrogate endpoint of late rectal toxicity in prostate cancer treated with radiotherapy.

PURPOSE: To predict the grade and incidence of late clinical rectal toxicity through short-term (1 year) mucosal alterations. METHODS AND MATERIALS: Patients with prostate adenocarcinoma treated with curative or adjuvant radiotherapy underwent proctoscopy a year after the course of radiotherapy. Mucosal changes were classified by the Vienna Rectoscopy Score (VRS). Late toxicity data were analyzed according to the Kaplan-Meier method. Comparison between prognosis groups was performed by log-rank analysis. RESULTS: After a median follow-up time of 45 months (range, 18-99), the 3-year incidence of grade ≥ 2 rectal late toxicity according to the criteria of the European Organization for Research and Treatment of Cancer and the Radiation Therapy Oncology Group was 24%, with all patients (24/24; 100%) experiencing rectal bleeding. The occurrence of grade ≥ 2 clinical rectal late toxicity was higher in patients with grade ≥ 2 (32% vs. 15 %, p = 0.02) or grade ≥ 3 VRS telangiectasia (47% vs. 17%, p ≤ 0.01) and an overall VRS score of ≥ 2 (31% vs. 16 %, p = 0.04) or ≥ 3 (48% vs. 17%, p = 0.01) at the 1-year proctoscopy. CONCLUSIONS: Early proctoscopy (1 year) predicts late rectal bleeding and therefore can be used as a surrogate endpoint for late rectal toxicity in studies aimed at reducing this frequent complication.

Quality of life and toxicity of stereotactic radiotherapy in pancreatic tumors: a case series.

AIM: To analyze the results of extracranial stereotactic radiotherapy (ESRT) experience in pancreatic cancer patients. METHODS: Four noncoplanar fixed beams were used in all patients. RESULTS: Analysis of 16 patients was carried out. Overall response rate was 56.2%. Fifteen patients experienced local and/or distant progression of disease (median follow-up: 24 months). Two-year local progression-free, distant progression-free, and overall survivals were 85.7%, 58.7%, and 50.0%, respectively. Toxicity was less than grade 2 in all, although 1 patient had severe duodenal bleeding. Quality of life scores were unchanged. CONCLUSIONS: ESRT was associated with low complication rate, and not worsening the patients' quality of life.

Neoadjuvant accelerated concomitant boost radiotherapy and multidrug chemotherapy in locally advanced rectal cancer: a dose-escalation study.

OBJECTIVES: To determine the maximal and safely dose of preoperative radiotherapy and concurrently intensified chemotherapy regimen (raltitrexed plus oxaliplatin) in locally advanced rectal cancer patients. METHODS: Patients with cT3-T4 and/or cN≥1 or locally recurrent rectal cancer were sequentially assigned to 4 treatment schedules of chemoradiation: standard radiotherapy (50.4 Gy/5.5 wk) plus raltitrexed (cohort A), accelerated radiotherapy (55 Gy/5 wk) plus raltitrexed (cohort B), standard radiotherapy plus raltitrexed and oxaliplatin (cohort C), accelerated radiotherapy plus raltitrexed and oxaliplatin (cohort D). Patients were treated in cohorts of 6 to 12 per group. The maximal tolerated dose was exceeded if more than one-third of patients in a given cohort experienced dose-limiting toxicity (DLT). DLT was defined as any grade ≥3 toxicity according to the Radiation Therapy Oncology Group criteria. RESULTS: Forty-six consecutive patients were enrolled. In cohort A, 6 patients received the planned treatment with no DLT. In cohort B, 1 of 8 patients experienced a DLT. In cohort C, a DLT occurred in 2 of 6 patients and therefore, a cohort expansion was required. Three of 16 patients treated at this dose level experienced a DLT. In addition, cohort D was expanded and DLT was found in 4 of 16 patients. Therefore, the maximal tolerated dose was not exceeded at any treatment level. CONCLUSIONS: An intensified regimen of chemoradiotherapy delivering raltitrexed and oxaliplatin concurrently with concomitant boost radiotherapy (55 Gy/5 wk) can be safely administered in patients with locally advanced rectal cancer. On the basis of these results, this intensified regimen could be tested in a phase II study.

Intensity-modulated radiotherapy with simultaneous integrated boost to dominant intraprostatic lesion: preliminary report on toxicity.

OBJECTIVES: To evaluate the feasibility of intensity-modulated radiotherapy with simultaneous integrated boost to the dominant intraprostatic lesion for definitive treatment of prostate cancer. MATERIALS AND METHODS: Patients were deemed eligible for the study if they had histologically proven stage cT2-T3 N0M0 prostate adenocarcinoma. In addition <20% risk of lymph nodal involvement according to Roach formula, was required for enrollment. Patients were treated with intensity-modulated radiotherapy with simultaneous integrated boost technique to the dominant intraprostatic lesion defined by magnetic resonance imaging. The prescribed dose to the prostate and seminal vesicles was 72 Gy (1.8 Gy per fraction). The dose delivered to the intraprostatic lesion received was 80 Gy (2 Gy per fraction). Acute gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated weekly during treatment, and at 1 and 3 months thereafter. Late GI and GU toxicity was evaluated by Kaplan Meier method. RESULTS: Forty patients were deemed evaluable. Acute and late GI and GU toxicity were evaluated in all patients. Two patients (5%) developed acute grade 3 GI toxicity and 1 patient (2.5%) developed acute grade 3 GU toxicity. No grade 4 acute GI or GU toxicity occurred. With a median follow-up of 19 months (interquartile range, 15 to 26 mo), the 2-year actuarial cumulative incidence of grade ≥2 rectal toxicity was 9.5%. The 2-year actuarial cumulative incidence of grade ≥2 urinary toxicity was 13.3%. CONCLUSIONS: Treatment related acute toxicity was low in our cohort. Prolonged observation with a larger series of patients is necessary to evaluate late toxicity and local control.

Concomitant boost radiotherapy and multidrug chemotherapy in the neoadjuvant treatment of locally advanced rectal cancer: results of a phase II study.

BACKGROUND: An intensified multidrug chemotherapy regimen (raltitrexed plus oxaliplatin, Tom-Ox) plus concomitant boost radiotherapy, in the neoadjuvant treatment of locally advanced rectal cancer patients, was shown feasible in our previous study. The aim of this study was to evaluate the efficacy in terms of pathologic complete response to pre-operative therapy. MATERIAL AND METHODS: A Phase II study was designed and clinical stage T3-T4 and/ or N ≥ 1 patients were treated with concomitant boost radiotherapy (55 Gy/5 weeks) plus concurrent chemotherapy (Tom-Ox). The primary endpoint was the assessment of efficacy in terms of clinical and pathologic response to pre-operative therapy. According to the Gehan's design study, 25 patients were enrolled. Toxicity was assessed according to the RTOG-EORTC and CTCAE v.3.0 criteria. RESULTS: Twenty-five consecutive patients were treated. Twenty-two of the 25 (88%) patients had a partial clinical response at the time of pre-operative magnetic resonance imaging (MRI). Only one patient showed progressive systemic disease at pre-surgical revaluation and was subjected only to biopsy to evaluate pathological response. Twenty-four patients (96%) underwent surgery. Overall, pathologic complete response was observed in eight patients (32%; CI 0.95:12-55%) and only microscopic tumor foci (pTmic) in two patients (pT0-mic: 40%; CI 0.95:18-63%). Nineteen patients (76%) showed tumor down-staging. Proctitis and/or diarrhea were the most frequent acute side effects experienced. Eighteen patients had grade 1-2 toxicity (77%); whereas two patients experienced grade 3 toxicity (8%). Two-year Local control and actuarial Disease Free Survival were 100% and 91%, respectively. CONCLUSION. An intensified regimen of concomitant boost radiotherapy plus concurrent raltitrexed and oxaliplatin, can be safely administered in patients with locally advanced rectal cancer. This regimen produces high rates of pathological complete response. Based on available data, this type of treatment could be offered to patients with more advanced tumors (T4 or local recurrence).

Forward planned intensity modulated radiotherapy (IMRT) for whole breast postoperative radiotherapy. Is it useful? When?

The purpose was to compare the dosimetric results observed in 201 breast cancer patients submitted to tangential forward intensity-modulated radiation therapy (IMRT) with those observed in 131 patients treated with a standard wedged 3D technique for postoperative treatment of whole breast, according to breast size and supraclavicular node irradiation. Following dosimetric parameters were used for the comparison: D(max), D(min), D(mean), V(95%) and V(107%) for the irradiated volume; D(max), D(mean), V(80%) and V(95%) for the ipsilateral lung; D(max), D(mean), V(80%) and V(95%) for the heart. Stratification was made according to breast size and supraclavicular (SCV) nodal irradiation. As respect to irradiated volume, a significant reduction of V(107%) (mean values: 7.0 ± 6.6 versus 2.4 ± 3.7, p < 0.001) and D(max) (mean % values: 111.2 ± 2.7 versus 107.7 ± 6.3, p < 0.001), and an increase of D(min) (mean % values: 65.0 ± 17.4 versus 74.9 ± 12.9, p < 0.001) were observed with forward IMRT. The homogeneity of dose distribution to target volume significantly improved with forward IMRT in all patient groups, irrespective of breast size or supraclavicular nodal irradiation. When patients treated with supraclavicular nodal irradiation were excluded from the analysis, forward IMRT slightly reduced V(80%) (mean values: 3.7 ± 2.6 versus 3.0 ± 2.4, p = 0.03) and V(95%) (mean values 1.9 ± 1.8 versus 1.2%± 1.5; p = 0.001) of the ipsilateral lung. The dose to the heart tended to be lower with IMRT but this difference was not statistically significant. Tangential forward IMRT in postoperative treatment of whole breast improved dosimetric parameters in terms of homogeneity of dose distribution to the target in a large sample of patients, independent of breast size or supraclavicular nodal irradiation. Lung irradiation was slightly reduced in patients not undergoing to supraclavicular irradiation.

Effect of whole pelvic radiotherapy for patients with locally advanced prostate cancer treated with radiotherapy and long-term androgen deprivation therapy.

PURPOSE: To evaluate the effect of whole pelvic radiotherapy (WPRT) in prostate cancer patients treated with RT and long-term (>1 year) androgen deprivation therapy (ADT). METHODS AND MATERIALS: Prostate cancer patients with high-risk features (Stage T3-T4 and/or Gleason score≥7 and/or prostate-specific antigen level≥20 ng/mL) who had undergone RT and long-term ADT were included in the present analysis. Patients with bowel inflammatory disease, colon diverticula, and colon diverticulitis were excluded from WPRT and treated with prostate-only radiotherapy (PORT). Patients were grouped according to nodal risk involvement as assessed by the Roach formula using different cutoff levels (15%, 20%, 25%, and 30%). Biochemical disease-free survival (bDFS) was analyzed in each group according to the RT type (WPRT or PORT). RESULTS: A total of 358 patients treated between 1994 and 2007 were included in the analysis (46.9% with WPRT and 53.1% with PORT). The median duration of ADT was 24 months (range, 12-38). With a median follow-up of 52 months (range, 20-150), the overall 4-year bDFS rate was 90.5%. The 4-year bDFS rate was similar between the patients who had undergone WPRT or PORT (90.4% vs. 90.5%; p=NS). However, in the group of patients with the greatest nodal risk (>30%), a significant bDFS improvement was recorded for the patients who had undergone WPRT (p=.03). No differences were seen in acute toxicity among the patients treated with WPRT or PORT. The late gastrointestinal toxicity was similar in patients treated with PORT or WPRT (p=NS). CONCLUSIONS: Our analysis has supported the use of WPRT in association with long-term ADT for patients with high-risk nodal involvement (>30%), although a definitive recommendation should be confirmed by a randomized trial.

3D conformal postoperative radiotherapy with concomitant boost in uterine cancer: results of a phase I-II study (ADA-RT-1).

OBJECTIVE: A phase I-II prospective clinical trial of adjuvant accelerated radiation therapy (ADA-RT-1 trial) was set up in order to investigate the feasibility and efficacy of a pelvic conformal radiotherapy technique with concomitant boost (CB technique) to the vaginal vault in high-risk uterine cancers. METHODS: Patients with uterine (endometrial cancer and sarcomas) and cervical neoplasm received external radiotherapy delivered in a short overall treatment time with a CB technique. The prescribed radiotherapy doses were 45/1.8 Gy/fraction to the pelvis and 55/2.2 Gy/fraction to the upper two-thirds of vagina plus resection lines in the parametria, respectively; treatment was administered in 25 fractions along 5 weeks. RESULTS: This study included 91 consecutive gynecological cancer patients (endometrial=72; cervical=10; sarcoma=9; median follow-up: 25 months, range: 5-72 months). Acute toxicity requiring treatment interruption (≥grade 3) was observed in 7 patients (7.7%). No case of vaginal recurrence was documented. Actuarial 3-year loco-regional control rate was 97.7%, whereas 3-year disease-free survival and overall survival rates were 88.5% and 94.0%, respectively. CONCLUSION: In summary, the CB technique provides a high probability of local control with acceptable toxicity and shortening of the overall treatment time; moreover, it may offer some advantages to resource constrained medical environments.

Feasibility study of moderately accelerated intensity-modulated radiotherapy plus concurrent weekly cisplatin after induction chemotherapy in locally advanced head-and neck cancer.

PURPOSE: To evaluate the feasibility and efficacy of moderately accelerated intensity-modulated radiation therapy (IMRT) along with weekly cisplatin, after induction chemotherapy, in patients with locally advanced unresectable head and neck cancer (HNC). METHODS AND MATERIALS: Patients with Stage III or IV locally advanced HNC, without progressive disease after three courses of induction chemotherapy, received concurrent chemo-IMRT (weekly cisplatin 30 mg/m(2) plus simultaneous integrated boost IMRT). A total of 67.5 Gy in 30 fractions were delivered to primary tumor and involved nodes, 60 Gy in 30 fractions to high-risk nodal areas, and 55.5 Gy in 30 fractions to low-risk nodal areas. RESULTS: In all, 36 patients (median age, 56 years) with International Union Against Cancer (UICC) Stage III (n = 5) and IV (n = 31) were included. Of the 36 patients, 17 had received CF (cisplatin and 5-fluorouracil (CF) and 19 had received docetaxel cisplatin and 5-fluorouracil (DCF). During concurrent chemoradiation, 11 of 36 patients (30.5%) experienced Grade III mucositis (CF, 47%; DCF, 15%; p < 0.04). Grade III pharyngeal-esophageal toxicity was observed in 5 of 19 patients (26.3%; CF, 0.0%; DCF, 26.3%; p = 0.02). Two patients died of complications (5.5%). After chemoradiation, the complete response rate was 63.8%. Two-year local control was 88.7%. Two-year progression free survival and overall survival were 74.5% and 60.9%, respectively. CONCLUSIONS: In our experience, a moderately accelerated chemo-IMRT was feasible after induction chemotherapy. However, a noteworthy early death rate of 5.5% was observed. Intensive supportive care strategies should be defined to better manage radiation-induced toxic effects. Longer follow-up is required to determine the incidence of late radiation toxicities and tumor control rates.