Giuseppe Girelli - Academia.edu (original) (raw)
Papers by Giuseppe Girelli
Radiotherapy and Oncology, 2011
Anticancer research, 2015
To report on clinical outcomes of prostate cancer patients treated with hypofrationated radiother... more To report on clinical outcomes of prostate cancer patients treated with hypofrationated radiotherapy employing a simultaneous integrated boost strategy. A consecutive series of 104 patients affected with prostate cancer was treated with intensity-modulated radiotherapy using a hypofractionated schedule and a simultaneous integrated boost consisting of 70 Gy (2.5 Gy daily) to the prostate gland, 63 Gy to the seminal vescicles (2.25 Gy daily) and 53.2 Gy to the pelvic nodes (1.9 Gy daily) when needed, delivered in 28 fractions. All patients underwent image-guided radiotherapy procedure consisting of daily cone-beam computed tomography. After a median observation time of 26 (range=15-48) months, the 3-year biochemical failure-free survival was 96.5% [95% confidence interval (CI)=89%-98%], 3-year cancer-specific survival was 98.5% (95% CI=91%-99%) and 3-year overall survival was 96.5% (95% CI=89%-98%). The gastrointestinal and genitourinary toxicity profiles were mild with fewer than 2%...
Tumori
Metastatic involvement of the penis is rare. About 80% of secondary lesions originate from pelvic... more Metastatic involvement of the penis is rare. About 80% of secondary lesions originate from pelvic primary tumors, mainly bladder and prostate. We present a case of prostatic mucinous adenocarcinoma with penile metastasis symptomatic for pain, which was treated with external-beam radiation (35 Gy/14 fractions; 2.5 Gy daily) combined with androgen deprivation, resulting in complete pain relief and objective response after treatment.
Tumori
The TomoTherapy Hi-Art II system is able to deliver dynamic intensity-modulated radiation therapy... more The TomoTherapy Hi-Art II system is able to deliver dynamic intensity-modulated radiation therapy within a helical geometry providing robust conformality and modulation, abrupt dose falloff, and reliable accuracy. A new upgrade named TomoDirect was introduced recently, allowing delivery of radiation at discrete angles with a fixed gantry. We present our preliminary clinical experience with TomoDirect. Three specific clinical contexts were chosen for the implementation of TomoDirect, namely palliation of bone metastasis pain (BP), whole brain radiation therapy for intracranial secondary lesions (WBRT), and adjuvant whole breast radiation therapy after conservative surgery for early stage breast cancer (AWBRT). After appropriate positioning, planning CT, contouring, and plan generation, all patients were treated with the TomoDirect upgrade of the TomoTherapy Hi-Art II system with different doses and fractionation according to clinical decision-making. Between May and December 2010, 41...
Background and purpose: To fit an NTCP model including clinical risk factors to late rectal toxic... more Background and purpose: To fit an NTCP model including clinical risk factors to late rectal toxicities after radiotherapy for prostate cancer. Methods and materials: Data of 669 patients were considered. The probability of late toxicity within 36 months (bleeding and incontinence) was fitted with the original and a modified Logit-EUD model, including clinical factors by fitting a subset specific TD 50 s: the ratio of TD 50 s with and without including the clinical variable was the dose-modifying factor (D mod ). Results: Abdominal surgery (surg) was a risk factor for G2-G3 bleeding, reflecting in a TD 50 = 82.7 Gy and 88.4 Gy for patients with and without surg (D mod = 0.94; 0.90 for G3 bleeding); acute toxicity was also an important risk factor for G2-G3 bleeding (D mod = 0.93). Concerning incontinence, surg and previous diseases of the colon were the clinical co-factors. D mod (surg) and D mod (colon) were 0.50 and 0.42, respectively for chronic incontinence and 0.73 and 0.64, respectively for mean incontinence score P1. Bestfit n values were 0.03-0.05 and 1 for bleeding and incontinence, respectively. The inclusion of clinical factors always improved the predictive value of the models. Conclusions: The inclusion of predisposing clinical factors improves NTCP estimation; the assessment of other clinical and genetic factors will be useful to reduce parameter uncertainties.
Breast Care, 2014
ogy, and systemic treatments have led to an increase in local control, with higher rates than tho... more ogy, and systemic treatments have led to an increase in local control, with higher rates than those observed in early randomized trials . It has been demonstrated that good local control translates into improved overall survival (OS) . The rationale for delivering an adjunctive radiation dose boosting the lumpectomy cavity is derived from several considerations: First, the radiobiological observation of a dose-response relationship for breast cancer; second, the pathological evidence of a higher microscopic tumor burden in proximity to the site of lumpectomy; and third, the clinical observation of the local pattern of failure close to the primary tumor location . Randomized phase III trials exploring the role of boosting the tumor bed demonstrated a relative reduction in local failure in the range of 20-50%, depending on risk factors of the patient cluster analyzed . However, in spite of this substantial clinical benefit, in several countries there has been a tendency to omit adjuvant WBRT after BCS, especially in women over 70-80 years, but also in younger patients, maybe due to the extended overall treatment time using a conventionally fractionated schedule and sequential boost approach . Hypofractionation (HF) (delivery of a larger dose per fraction in shorter overall time) and concurrent boost (delivery of a synchronous adjunctive dose to the tumor bed) represent a useful option to optimize treatment both for patients and healthcare providers .
Radiotherapy and Oncology, 2004
Background and purpose: Recent investigations demonstrated a significant correlation between rect... more Background and purpose: Recent investigations demonstrated a significant correlation between rectal dose-volume patterns and late rectal toxicity. The reduction of the DVH to a value expressing the probability of complication would be suitable. To fit different normal tissue complication probability (NTCP) models to clinical outcome on late rectal bleeding after external beam radiotherapy (RT) for prostate cancer.
Cancer Investigation, 2014
Purpose: To evaluate the feasibility and response to palliative radiotherapy delivered with stati... more Purpose: To evaluate the feasibility and response to palliative radiotherapy delivered with static ports of tomotherapy-TomoDirect (TD) in patients affected with painful bone metastases from solid tumors. Methods: A prospective cohort of 130 patients (185 osseous lesions) was treated between 2010 and 2013 with TD. Three fractionation schedules were employed according to clinical decision-making (3 Gy × 10; 4 Gy × 5; 8 Gy × 1). Pain response was investigated at 2 weeks and 2 months (for evaluable patients). The Numeric Rating Scale (NRS-11) was used to assess pain. Response rates to radiotherapy were calculated following the criteria of the International Bone Metastases Consensus Group (IBMCG), accounting for the use of concomitant analgesics (response: complete or partial; non-response: stable pain, pain progression or "other"). Analgesic consumption was recalculated into the daily oral morphine-equivalent dose (OMED). Results: Most of the patients had 1-2 bone metastases (91); those with multiple lesions mostly had a metachronous presentation (60%). Synchronous lesions were mainly approached with multiple plans (63%). Most treatments employed 3-4 fields (77%). Treatment times ranged from 255 to 939 s depending on fractionation, fields, and target lesions number. At 2 weeks, the median self-reported worst pain decreased significantly as median oral morphine-equivalent dose regardless of fractionation used. The response rate according to the IBMCG-based response categories ranged from 45 to 55%. Pain relief duration seems (response at 2 months) slightly inferior with the single fraction approach, with a higher re-treatment rate. At 2 weeks, the median self-reported worst pain and OMED significantly decreased regardless of fractionation (response rate: 49-55%). Pain relief decreased at 2 months, especially for single fraction (higher re-treatment rate).
Medical Oncology, 2013
Accelerated hypofractionation (HF) using larger dose per fraction, delivered in fewer fractions o... more Accelerated hypofractionation (HF) using larger dose per fraction, delivered in fewer fractions over a shorter overall treatment time, is presently a consistent possibility for adjuvant whole breast radiation (WBRT) after breast-conserving surgery for early breast cancer (EBC). Between 2005 and 2008, we submitted 375 consecutive patients to accelerated hypofractionated WBRT after breast-conserving surgery for EBC. The basic course of radiation consisted of 45 Gy in 20 fractions over 4 weeks to the whole breast (2.25 Gy daily) with an additional daily concomitant boost of 0.25 Gy up to 50 Gy to the surgical bed. Overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS) and local control (LC) were assessed. Late toxicity was scored according to the CTCAE v3.0; acute toxicity using the RTOG/EORTC toxicity scale. Cosmesis was assessed comparing treated and untreated breast. Quality of life (QoL) was determined using EORTC QLQ-C30/QLQ-BR23 questionnaires. With a median follow-up of 60 months (range 42-88), 5 years OS, CSS, DFS and LC were 97.6, 99.4, 96.6 and 100 %, respectively. Late skin and subcutaneous toxicity was generally mild, with few events [ grade 2 observed. Cosmetic results were excellent in 75.7 % of patients, good in 20 % and fair in 4.3 %. QoL, assessed both through QLQ-C30/QLQ-BR23, was generally favorable, within the functioning and symptoms domains. Our study is another proof of principle that HF WBRT with a concurrent boost dose to the surgical cavity represents a safe and effective postoperative treatment modality with excellent local control and survival, consistent cosmetic results and mild toxicity.
Radiotherapy and Oncology, 2011
Background and purpose: To fit an NTCP model including clinical risk factors to late rectal toxic... more Background and purpose: To fit an NTCP model including clinical risk factors to late rectal toxicities after radiotherapy for prostate cancer. Methods and materials: Data of 669 patients were considered. The probability of late toxicity within 36 months (bleeding and incontinence) was fitted with the original and a modified Logit-EUD model, including clinical factors by fitting a subset specific TD 50 s: the ratio of TD 50 s with and without including the clinical variable was the dose-modifying factor (D mod ). Results: Abdominal surgery (surg) was a risk factor for G2-G3 bleeding, reflecting in a TD 50 = 82.7 Gy and 88.4 Gy for patients with and without surg (D mod = 0.94; 0.90 for G3 bleeding); acute toxicity was also an important risk factor for G2-G3 bleeding (D mod = 0.93). Concerning incontinence, surg and previous diseases of the colon were the clinical co-factors. D mod (surg) and D mod (colon) were 0.50 and 0.42, respectively for chronic incontinence and 0.73 and 0.64, respectively for mean incontinence score P1. Bestfit n values were 0.03-0.05 and 1 for bleeding and incontinence, respectively. The inclusion of clinical factors always improved the predictive value of the models. Conclusions: The inclusion of predisposing clinical factors improves NTCP estimation; the assessment of other clinical and genetic factors will be useful to reduce parameter uncertainties.
Radiotherapy and Oncology, 2014
Purpose: To prospectively evaluate long-term late rectal bleeding (lrb) and faecal incontinence (... more Purpose: To prospectively evaluate long-term late rectal bleeding (lrb) and faecal incontinence (linc) after high-dose radiotherapy (RT) for prostate cancer in the AIROPROS 0102 population, and to assess clinical/ dosimetric risk factors. Materials and methods: Questionnaires of 515 patients with G0 baseline incontinence and bleeding scores (follow-up P6 years) were analysed. Correlations between lrb/linc and many clinical and dosimetric parameters were investigated by univariate and multivariate logistic analyses. The correlation between lrb/linc and symptoms during the first 3 years after RT was also investigated. Results: Of 515 patients lrb G1, G2 and G3 was found in 32 (6.1%), 2 (0.4%) and 3 (0.6%) patients while linc G1, G2 and G3 was detected in 50 (9.7%), 3 (0.6%) and 3 (0.6%), respectively. The prevalence of G2-G3 lrb events was significantly reduced compared to the first 3-years (1% vs 2.7%, p = 0.016) PG1 lrb was significantly associated with V75Gy (OR = 1.07). In multivariate analysis, PG1 linc was associated with V40Gy (OR = 1.015), use of antihypertensive medication (OR = 0.38), abdominal surgery before RT (OR = 4.7), haemorrhoids (OR = 2.6), and G2-G3 acute faecal incontinence (OR = 4.4), a nomogram to predict the risk of long-term PG1 linc was proposed.
Radiotherapy and Oncology, 2014
Background and purpose: DUE01 is an observational study aimed at developing predictive models of ... more Background and purpose: DUE01 is an observational study aimed at developing predictive models of genito-urinary toxicity of patients treated for prostate cancer with conventional (1.8-2 Gy/fr, CONV) or moderate hypo-fractionation (2.35-2.7 Gy/fr, HYPO). The current analysis focused on the relationship between bladder DVH/DSH and the risk of International Prostate Symptoms Score (IPSS) P 15/20 at the end of radiotherapy. Materials and methods: Planning and relevant clinical parameters were prospectively collected, including DVH/DSH, LQ-corrected (DVHc/DSHc) and weekly (DVHw/DSHw) histograms. Best parameters were selected by the differences between patients with/without IPSS P 15/20 at the end of radiotherapy. Logistic uni-and backward multi-variable (MVA) analyses were performed. Results: Data of 247 patients were available (CONV: 116, HYPO: 131). Absolute DVHw/DSHw and DVHc/ DSHc predicted the risk of IPSS P 15 at the end of radiotherapy (n = 77/247); an MVA model including baseline IPSS, anti-hypertensive, T stage, the absolute surface receiving P8.5 Gy/week and P12.5 Gy/ week was developed (AUC = 0.78, 95% CI: 0.72-0.83). Similar AUC values were found if replacing DSHw with DVHw/DVHc/DSHc parameters. The impact of dose-volume/surface parameters remained when excluding patients with baseline IPSS P 15 and in HYPO. IPSS P 20 at the end of radiotherapy (n = 27/ 247) was mainly correlated to baseline IPSS and T stage. Conclusions: Although the baseline IPSS was the main predictor, constraining v8.5w < 56 cc and v12.5w < 5 cc may significantly reduce acute GU toxicity.
International Journal of Radiation Oncology Biology Physics, 2008
International Journal of Radiation Oncology*Biology*Physics, 2003
International Journal of Radiation Oncology*Biology*Physics, 2008
International Journal of Radiation Oncology*Biology*Physics, 2009
The main purpose of this work was to try to elucidate why, despite excellent rectal dose-volume h... more The main purpose of this work was to try to elucidate why, despite excellent rectal dose-volume histograms (DVHs), some patients treated for prostate cancer exhibit late rectal bleeding (LRB) and others with poor DVHs do not. Thirty-five genes involved in DNA repair/radiation response were analyzed in patients accrued in the AIROPROS 0101 trial, which investigated the correlation between LRB and dosimetric parameters. Thirty patients undergoing conformal radiotherapy with prescription doses higher than 70 Gy (minimum follow-up, 48 months) were selected: 10 patients in the low-risk group (rectal DVH with the percent volume of rectum receiving more than 70 Gy [V70Gy] &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 20% and the percent volume of rectum receiving more than 50 Gy [V50Gy] &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 55%) with Grade 2 or Grade 3 (G2-G3) LRB, 10 patients in the high-risk group (V70Gy &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 25% and V50Gy &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 60%) with G2-G3 LRB, and 10 patients in the high-risk group with no toxicity. Quantitative reverse-transcriptase polymerase chain reaction was performed on RNA from lymphoblastoid cell lines obtained from Epstein-Barr virus-immortalized peripheral-blood mononucleated cells and on peripheral blood mononucleated cells. Interexpression levels were compared by using the Kruskal-Wallis test. Intergroup comparison showed many constitutive differences: nine genes were significantly down-regulated in the low-risk bleeder group vs. the high-risk bleeder and high-risk nonbleeder groups: AKR1B1 (p = 0.019), BAZ1B (p = 0.042), LSM7 (p = 0.0016), MRPL23 (p = 0.015), NUDT1 (p = 0.0031), PSMB4 (p = 0.079), PSMD1 (p = 0.062), SEC22L1 (p = 0.040), and UBB (p = 0.018). Four genes were significantly upregulated in the high-risk nonbleeder group than in the other groups: DDX17 (p = 0.048), DRAP1 (p = 0.0025), RAD23 (p = 0.015), and SRF (p = 0.024). For most of these genes, it was possible to establish a cut-off value that correctly classified most patients. The predictive value of sensitivity and resistance to LRB of the genes identified by the study is promising and should be tested in a larger data set.
International Journal of Radiation Oncology*Biology*Physics, 2007
test the ability of Amifostine, a cytoprotective agent, to reduce the acute toxicity of combined ... more test the ability of Amifostine, a cytoprotective agent, to reduce the acute toxicity of combined chemotherapy with extended field radiotherapy and brachytherapy. Materials/Methods: RTOG 0116 was designed as a two-part trial. Part one delivered extended field irradiation and brachytherapy combined with weekly cisplatin chemotherapy, part two adds Amifostine. Based on the estimate of toxicity in part one, 16 evaluable patients are required to detect a 40% reduction in grade 3&4 non-hematologic toxicity (excluding grade 3 leukopenia) from 77% to 46%. Eligibility included patients with squamous, adeno or adenosquamous carcinoma of the cervix with evidence for high common iliac or para-aortic metastasis. Patients were treated with extended field radiotherapy from the T11/T12 interspace through the pelvis for a total dose of 45 Gy in 25 fractions with intracavitary irradiation. IMRT was not allowed. The final point A dose was 85 Gy LDR equivalent. HDR was allowed. The positive para-aortic and iliac nodes were to be boosted to a total dose of 54 to 59.4 Gy at the investigator's discretion. Cisplatin at a dose of 40 mg/m 2 was delivered weekly during external beam and once with brachytherapy. Amifostine at 500 mg was to be delivered with every fraction of radiotherapy and brachytherapy in two divided subcutaneous injections. Results: The study opened on 8/1/01 and closed 2/26/07 after accruing 45 patients, 18 for the second part with amifostine. This analysis reports the primary endpoint for the patients entered on the second part of the trial. Of these 18 patients 2 were ineligible, one withdrew from trial and one patient does not have toxicity data available. Seven of the remaining 14 patients (50%) were noted to have para-aortic metastasis with the remaining having high common iliac metastasis. Follow-up ranged from 0.3-22.6 months with a median of 8.9 months.
International Journal of Radiation Oncology*Biology*Physics, 2009
Purpose/Objective(s): To evaluate and discuss the role of specific types of abdominal surgery (SU... more Purpose/Objective(s): To evaluate and discuss the role of specific types of abdominal surgery (SURG) before radiation therapy (RT) as a risk factor for late rectal bleeding (lrb) in prostate cancer patients (pts) accrued in AIROPROS 0102 trial. Materials/Methods: Results concerning lrb in 718 pts with a complete follow-up of 36 mos are here analysed. Previous multivariate logistic analysis (MVA) (Fiorino IJROBP 08 and Fellin RO submitted) showed that lrb was highly correlated with the % volume of rectum receiving more than 75 Gy (V75Gy) (continuous variable, OR = 1.06), SURG (OR = 2.24), acute G2-G3 lower gastro-intestinal toxicity (OR = 1.80) and androgen deprivation (protective role, OR = 0.63). This work focuses on the group of pts who underwent SURG before RT to clarify if a different dose-volume relationship is present and to evaluate the possible role and weight of different types of abdominal surgery (rectum-sigma resection, kidney resection, cholecystectomy or appendectomy) on lrb. Results: 52/718 (7.2%) pts were scored as bleeders: 28/718 (3.9%) G2 and 24/718 (3.3%) G3. n the subgroup of pts previously submitted to SURG (n = 69; 8 G2-G3 lrb), the % volume of rectum receiving more than 70 Gy (V70Gy) was found to be highly correlated with lrb (continuous variable, OR = 1.10,p = 0.012) while V70Gy was of minor importance in the population of pts who did not undergo SURG prior to RT (OR = 1.011, p = 0.09). ROC curves using V70Gy as classifying criterion suggest that V70Gy is a useful constraint for SURG pts (cut-off V70Gy=20%). When considering the kind of surgery, cholecystectomy was found to be highly correlated with lrb (univariate analysis): OR = 4.3 and p = 0.006 when G2-G3 lrb is considered and OR = 5.4 and p = 0.01 when focusing on G3 lrb. Considering MVA (including dosimetric and clinical factors), G2-G3 lrb was significantly correlated to appendectomy (OR = 2.5, p = 0.13), cholecystectomy (OR = 6.1, p = 0.002), androgen deprivation (protective factor, OR = 0.57, p = 0.09) and V75Gy (continuous variable, OR = 1.063, p = 0.004). G3 lrb was mainly correlated to appendectomy (OR = 5.2, p = 0.07) and cholecystectomy (OR = 4.2, p = 0.038).
International Journal of Radiation Oncology*Biology*Physics, 2005
receiving HDR ϩ IMRT. Preliminary results with HDR monotherapy compare favorably to EBRT, LDR Ϯ E... more receiving HDR ϩ IMRT. Preliminary results with HDR monotherapy compare favorably to EBRT, LDR Ϯ EBRT, and HDR ϩ IMRT, both with regard to PSA disease free survival, and complications. With regard to implant technique, HDR brachytherapy offers other advantages over LDR, such as no radiation exposure to hospital personnel, no seed migration, greater dose flexibility and precision of radiation dose delivery. Larger volumes can be treated with HDR. By omitting EBRT, rectal complications may be reduced.
Radiotherapy and Oncology, 2011
Anticancer research, 2015
To report on clinical outcomes of prostate cancer patients treated with hypofrationated radiother... more To report on clinical outcomes of prostate cancer patients treated with hypofrationated radiotherapy employing a simultaneous integrated boost strategy. A consecutive series of 104 patients affected with prostate cancer was treated with intensity-modulated radiotherapy using a hypofractionated schedule and a simultaneous integrated boost consisting of 70 Gy (2.5 Gy daily) to the prostate gland, 63 Gy to the seminal vescicles (2.25 Gy daily) and 53.2 Gy to the pelvic nodes (1.9 Gy daily) when needed, delivered in 28 fractions. All patients underwent image-guided radiotherapy procedure consisting of daily cone-beam computed tomography. After a median observation time of 26 (range=15-48) months, the 3-year biochemical failure-free survival was 96.5% [95% confidence interval (CI)=89%-98%], 3-year cancer-specific survival was 98.5% (95% CI=91%-99%) and 3-year overall survival was 96.5% (95% CI=89%-98%). The gastrointestinal and genitourinary toxicity profiles were mild with fewer than 2%...
Tumori
Metastatic involvement of the penis is rare. About 80% of secondary lesions originate from pelvic... more Metastatic involvement of the penis is rare. About 80% of secondary lesions originate from pelvic primary tumors, mainly bladder and prostate. We present a case of prostatic mucinous adenocarcinoma with penile metastasis symptomatic for pain, which was treated with external-beam radiation (35 Gy/14 fractions; 2.5 Gy daily) combined with androgen deprivation, resulting in complete pain relief and objective response after treatment.
Tumori
The TomoTherapy Hi-Art II system is able to deliver dynamic intensity-modulated radiation therapy... more The TomoTherapy Hi-Art II system is able to deliver dynamic intensity-modulated radiation therapy within a helical geometry providing robust conformality and modulation, abrupt dose falloff, and reliable accuracy. A new upgrade named TomoDirect was introduced recently, allowing delivery of radiation at discrete angles with a fixed gantry. We present our preliminary clinical experience with TomoDirect. Three specific clinical contexts were chosen for the implementation of TomoDirect, namely palliation of bone metastasis pain (BP), whole brain radiation therapy for intracranial secondary lesions (WBRT), and adjuvant whole breast radiation therapy after conservative surgery for early stage breast cancer (AWBRT). After appropriate positioning, planning CT, contouring, and plan generation, all patients were treated with the TomoDirect upgrade of the TomoTherapy Hi-Art II system with different doses and fractionation according to clinical decision-making. Between May and December 2010, 41...
Background and purpose: To fit an NTCP model including clinical risk factors to late rectal toxic... more Background and purpose: To fit an NTCP model including clinical risk factors to late rectal toxicities after radiotherapy for prostate cancer. Methods and materials: Data of 669 patients were considered. The probability of late toxicity within 36 months (bleeding and incontinence) was fitted with the original and a modified Logit-EUD model, including clinical factors by fitting a subset specific TD 50 s: the ratio of TD 50 s with and without including the clinical variable was the dose-modifying factor (D mod ). Results: Abdominal surgery (surg) was a risk factor for G2-G3 bleeding, reflecting in a TD 50 = 82.7 Gy and 88.4 Gy for patients with and without surg (D mod = 0.94; 0.90 for G3 bleeding); acute toxicity was also an important risk factor for G2-G3 bleeding (D mod = 0.93). Concerning incontinence, surg and previous diseases of the colon were the clinical co-factors. D mod (surg) and D mod (colon) were 0.50 and 0.42, respectively for chronic incontinence and 0.73 and 0.64, respectively for mean incontinence score P1. Bestfit n values were 0.03-0.05 and 1 for bleeding and incontinence, respectively. The inclusion of clinical factors always improved the predictive value of the models. Conclusions: The inclusion of predisposing clinical factors improves NTCP estimation; the assessment of other clinical and genetic factors will be useful to reduce parameter uncertainties.
Breast Care, 2014
ogy, and systemic treatments have led to an increase in local control, with higher rates than tho... more ogy, and systemic treatments have led to an increase in local control, with higher rates than those observed in early randomized trials . It has been demonstrated that good local control translates into improved overall survival (OS) . The rationale for delivering an adjunctive radiation dose boosting the lumpectomy cavity is derived from several considerations: First, the radiobiological observation of a dose-response relationship for breast cancer; second, the pathological evidence of a higher microscopic tumor burden in proximity to the site of lumpectomy; and third, the clinical observation of the local pattern of failure close to the primary tumor location . Randomized phase III trials exploring the role of boosting the tumor bed demonstrated a relative reduction in local failure in the range of 20-50%, depending on risk factors of the patient cluster analyzed . However, in spite of this substantial clinical benefit, in several countries there has been a tendency to omit adjuvant WBRT after BCS, especially in women over 70-80 years, but also in younger patients, maybe due to the extended overall treatment time using a conventionally fractionated schedule and sequential boost approach . Hypofractionation (HF) (delivery of a larger dose per fraction in shorter overall time) and concurrent boost (delivery of a synchronous adjunctive dose to the tumor bed) represent a useful option to optimize treatment both for patients and healthcare providers .
Radiotherapy and Oncology, 2004
Background and purpose: Recent investigations demonstrated a significant correlation between rect... more Background and purpose: Recent investigations demonstrated a significant correlation between rectal dose-volume patterns and late rectal toxicity. The reduction of the DVH to a value expressing the probability of complication would be suitable. To fit different normal tissue complication probability (NTCP) models to clinical outcome on late rectal bleeding after external beam radiotherapy (RT) for prostate cancer.
Cancer Investigation, 2014
Purpose: To evaluate the feasibility and response to palliative radiotherapy delivered with stati... more Purpose: To evaluate the feasibility and response to palliative radiotherapy delivered with static ports of tomotherapy-TomoDirect (TD) in patients affected with painful bone metastases from solid tumors. Methods: A prospective cohort of 130 patients (185 osseous lesions) was treated between 2010 and 2013 with TD. Three fractionation schedules were employed according to clinical decision-making (3 Gy × 10; 4 Gy × 5; 8 Gy × 1). Pain response was investigated at 2 weeks and 2 months (for evaluable patients). The Numeric Rating Scale (NRS-11) was used to assess pain. Response rates to radiotherapy were calculated following the criteria of the International Bone Metastases Consensus Group (IBMCG), accounting for the use of concomitant analgesics (response: complete or partial; non-response: stable pain, pain progression or "other"). Analgesic consumption was recalculated into the daily oral morphine-equivalent dose (OMED). Results: Most of the patients had 1-2 bone metastases (91); those with multiple lesions mostly had a metachronous presentation (60%). Synchronous lesions were mainly approached with multiple plans (63%). Most treatments employed 3-4 fields (77%). Treatment times ranged from 255 to 939 s depending on fractionation, fields, and target lesions number. At 2 weeks, the median self-reported worst pain decreased significantly as median oral morphine-equivalent dose regardless of fractionation used. The response rate according to the IBMCG-based response categories ranged from 45 to 55%. Pain relief duration seems (response at 2 months) slightly inferior with the single fraction approach, with a higher re-treatment rate. At 2 weeks, the median self-reported worst pain and OMED significantly decreased regardless of fractionation (response rate: 49-55%). Pain relief decreased at 2 months, especially for single fraction (higher re-treatment rate).
Medical Oncology, 2013
Accelerated hypofractionation (HF) using larger dose per fraction, delivered in fewer fractions o... more Accelerated hypofractionation (HF) using larger dose per fraction, delivered in fewer fractions over a shorter overall treatment time, is presently a consistent possibility for adjuvant whole breast radiation (WBRT) after breast-conserving surgery for early breast cancer (EBC). Between 2005 and 2008, we submitted 375 consecutive patients to accelerated hypofractionated WBRT after breast-conserving surgery for EBC. The basic course of radiation consisted of 45 Gy in 20 fractions over 4 weeks to the whole breast (2.25 Gy daily) with an additional daily concomitant boost of 0.25 Gy up to 50 Gy to the surgical bed. Overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS) and local control (LC) were assessed. Late toxicity was scored according to the CTCAE v3.0; acute toxicity using the RTOG/EORTC toxicity scale. Cosmesis was assessed comparing treated and untreated breast. Quality of life (QoL) was determined using EORTC QLQ-C30/QLQ-BR23 questionnaires. With a median follow-up of 60 months (range 42-88), 5 years OS, CSS, DFS and LC were 97.6, 99.4, 96.6 and 100 %, respectively. Late skin and subcutaneous toxicity was generally mild, with few events [ grade 2 observed. Cosmetic results were excellent in 75.7 % of patients, good in 20 % and fair in 4.3 %. QoL, assessed both through QLQ-C30/QLQ-BR23, was generally favorable, within the functioning and symptoms domains. Our study is another proof of principle that HF WBRT with a concurrent boost dose to the surgical cavity represents a safe and effective postoperative treatment modality with excellent local control and survival, consistent cosmetic results and mild toxicity.
Radiotherapy and Oncology, 2011
Background and purpose: To fit an NTCP model including clinical risk factors to late rectal toxic... more Background and purpose: To fit an NTCP model including clinical risk factors to late rectal toxicities after radiotherapy for prostate cancer. Methods and materials: Data of 669 patients were considered. The probability of late toxicity within 36 months (bleeding and incontinence) was fitted with the original and a modified Logit-EUD model, including clinical factors by fitting a subset specific TD 50 s: the ratio of TD 50 s with and without including the clinical variable was the dose-modifying factor (D mod ). Results: Abdominal surgery (surg) was a risk factor for G2-G3 bleeding, reflecting in a TD 50 = 82.7 Gy and 88.4 Gy for patients with and without surg (D mod = 0.94; 0.90 for G3 bleeding); acute toxicity was also an important risk factor for G2-G3 bleeding (D mod = 0.93). Concerning incontinence, surg and previous diseases of the colon were the clinical co-factors. D mod (surg) and D mod (colon) were 0.50 and 0.42, respectively for chronic incontinence and 0.73 and 0.64, respectively for mean incontinence score P1. Bestfit n values were 0.03-0.05 and 1 for bleeding and incontinence, respectively. The inclusion of clinical factors always improved the predictive value of the models. Conclusions: The inclusion of predisposing clinical factors improves NTCP estimation; the assessment of other clinical and genetic factors will be useful to reduce parameter uncertainties.
Radiotherapy and Oncology, 2014
Purpose: To prospectively evaluate long-term late rectal bleeding (lrb) and faecal incontinence (... more Purpose: To prospectively evaluate long-term late rectal bleeding (lrb) and faecal incontinence (linc) after high-dose radiotherapy (RT) for prostate cancer in the AIROPROS 0102 population, and to assess clinical/ dosimetric risk factors. Materials and methods: Questionnaires of 515 patients with G0 baseline incontinence and bleeding scores (follow-up P6 years) were analysed. Correlations between lrb/linc and many clinical and dosimetric parameters were investigated by univariate and multivariate logistic analyses. The correlation between lrb/linc and symptoms during the first 3 years after RT was also investigated. Results: Of 515 patients lrb G1, G2 and G3 was found in 32 (6.1%), 2 (0.4%) and 3 (0.6%) patients while linc G1, G2 and G3 was detected in 50 (9.7%), 3 (0.6%) and 3 (0.6%), respectively. The prevalence of G2-G3 lrb events was significantly reduced compared to the first 3-years (1% vs 2.7%, p = 0.016) PG1 lrb was significantly associated with V75Gy (OR = 1.07). In multivariate analysis, PG1 linc was associated with V40Gy (OR = 1.015), use of antihypertensive medication (OR = 0.38), abdominal surgery before RT (OR = 4.7), haemorrhoids (OR = 2.6), and G2-G3 acute faecal incontinence (OR = 4.4), a nomogram to predict the risk of long-term PG1 linc was proposed.
Radiotherapy and Oncology, 2014
Background and purpose: DUE01 is an observational study aimed at developing predictive models of ... more Background and purpose: DUE01 is an observational study aimed at developing predictive models of genito-urinary toxicity of patients treated for prostate cancer with conventional (1.8-2 Gy/fr, CONV) or moderate hypo-fractionation (2.35-2.7 Gy/fr, HYPO). The current analysis focused on the relationship between bladder DVH/DSH and the risk of International Prostate Symptoms Score (IPSS) P 15/20 at the end of radiotherapy. Materials and methods: Planning and relevant clinical parameters were prospectively collected, including DVH/DSH, LQ-corrected (DVHc/DSHc) and weekly (DVHw/DSHw) histograms. Best parameters were selected by the differences between patients with/without IPSS P 15/20 at the end of radiotherapy. Logistic uni-and backward multi-variable (MVA) analyses were performed. Results: Data of 247 patients were available (CONV: 116, HYPO: 131). Absolute DVHw/DSHw and DVHc/ DSHc predicted the risk of IPSS P 15 at the end of radiotherapy (n = 77/247); an MVA model including baseline IPSS, anti-hypertensive, T stage, the absolute surface receiving P8.5 Gy/week and P12.5 Gy/ week was developed (AUC = 0.78, 95% CI: 0.72-0.83). Similar AUC values were found if replacing DSHw with DVHw/DVHc/DSHc parameters. The impact of dose-volume/surface parameters remained when excluding patients with baseline IPSS P 15 and in HYPO. IPSS P 20 at the end of radiotherapy (n = 27/ 247) was mainly correlated to baseline IPSS and T stage. Conclusions: Although the baseline IPSS was the main predictor, constraining v8.5w < 56 cc and v12.5w < 5 cc may significantly reduce acute GU toxicity.
International Journal of Radiation Oncology Biology Physics, 2008
International Journal of Radiation Oncology*Biology*Physics, 2003
International Journal of Radiation Oncology*Biology*Physics, 2008
International Journal of Radiation Oncology*Biology*Physics, 2009
The main purpose of this work was to try to elucidate why, despite excellent rectal dose-volume h... more The main purpose of this work was to try to elucidate why, despite excellent rectal dose-volume histograms (DVHs), some patients treated for prostate cancer exhibit late rectal bleeding (LRB) and others with poor DVHs do not. Thirty-five genes involved in DNA repair/radiation response were analyzed in patients accrued in the AIROPROS 0101 trial, which investigated the correlation between LRB and dosimetric parameters. Thirty patients undergoing conformal radiotherapy with prescription doses higher than 70 Gy (minimum follow-up, 48 months) were selected: 10 patients in the low-risk group (rectal DVH with the percent volume of rectum receiving more than 70 Gy [V70Gy] &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 20% and the percent volume of rectum receiving more than 50 Gy [V50Gy] &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 55%) with Grade 2 or Grade 3 (G2-G3) LRB, 10 patients in the high-risk group (V70Gy &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 25% and V50Gy &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 60%) with G2-G3 LRB, and 10 patients in the high-risk group with no toxicity. Quantitative reverse-transcriptase polymerase chain reaction was performed on RNA from lymphoblastoid cell lines obtained from Epstein-Barr virus-immortalized peripheral-blood mononucleated cells and on peripheral blood mononucleated cells. Interexpression levels were compared by using the Kruskal-Wallis test. Intergroup comparison showed many constitutive differences: nine genes were significantly down-regulated in the low-risk bleeder group vs. the high-risk bleeder and high-risk nonbleeder groups: AKR1B1 (p = 0.019), BAZ1B (p = 0.042), LSM7 (p = 0.0016), MRPL23 (p = 0.015), NUDT1 (p = 0.0031), PSMB4 (p = 0.079), PSMD1 (p = 0.062), SEC22L1 (p = 0.040), and UBB (p = 0.018). Four genes were significantly upregulated in the high-risk nonbleeder group than in the other groups: DDX17 (p = 0.048), DRAP1 (p = 0.0025), RAD23 (p = 0.015), and SRF (p = 0.024). For most of these genes, it was possible to establish a cut-off value that correctly classified most patients. The predictive value of sensitivity and resistance to LRB of the genes identified by the study is promising and should be tested in a larger data set.
International Journal of Radiation Oncology*Biology*Physics, 2007
test the ability of Amifostine, a cytoprotective agent, to reduce the acute toxicity of combined ... more test the ability of Amifostine, a cytoprotective agent, to reduce the acute toxicity of combined chemotherapy with extended field radiotherapy and brachytherapy. Materials/Methods: RTOG 0116 was designed as a two-part trial. Part one delivered extended field irradiation and brachytherapy combined with weekly cisplatin chemotherapy, part two adds Amifostine. Based on the estimate of toxicity in part one, 16 evaluable patients are required to detect a 40% reduction in grade 3&4 non-hematologic toxicity (excluding grade 3 leukopenia) from 77% to 46%. Eligibility included patients with squamous, adeno or adenosquamous carcinoma of the cervix with evidence for high common iliac or para-aortic metastasis. Patients were treated with extended field radiotherapy from the T11/T12 interspace through the pelvis for a total dose of 45 Gy in 25 fractions with intracavitary irradiation. IMRT was not allowed. The final point A dose was 85 Gy LDR equivalent. HDR was allowed. The positive para-aortic and iliac nodes were to be boosted to a total dose of 54 to 59.4 Gy at the investigator's discretion. Cisplatin at a dose of 40 mg/m 2 was delivered weekly during external beam and once with brachytherapy. Amifostine at 500 mg was to be delivered with every fraction of radiotherapy and brachytherapy in two divided subcutaneous injections. Results: The study opened on 8/1/01 and closed 2/26/07 after accruing 45 patients, 18 for the second part with amifostine. This analysis reports the primary endpoint for the patients entered on the second part of the trial. Of these 18 patients 2 were ineligible, one withdrew from trial and one patient does not have toxicity data available. Seven of the remaining 14 patients (50%) were noted to have para-aortic metastasis with the remaining having high common iliac metastasis. Follow-up ranged from 0.3-22.6 months with a median of 8.9 months.
International Journal of Radiation Oncology*Biology*Physics, 2009
Purpose/Objective(s): To evaluate and discuss the role of specific types of abdominal surgery (SU... more Purpose/Objective(s): To evaluate and discuss the role of specific types of abdominal surgery (SURG) before radiation therapy (RT) as a risk factor for late rectal bleeding (lrb) in prostate cancer patients (pts) accrued in AIROPROS 0102 trial. Materials/Methods: Results concerning lrb in 718 pts with a complete follow-up of 36 mos are here analysed. Previous multivariate logistic analysis (MVA) (Fiorino IJROBP 08 and Fellin RO submitted) showed that lrb was highly correlated with the % volume of rectum receiving more than 75 Gy (V75Gy) (continuous variable, OR = 1.06), SURG (OR = 2.24), acute G2-G3 lower gastro-intestinal toxicity (OR = 1.80) and androgen deprivation (protective role, OR = 0.63). This work focuses on the group of pts who underwent SURG before RT to clarify if a different dose-volume relationship is present and to evaluate the possible role and weight of different types of abdominal surgery (rectum-sigma resection, kidney resection, cholecystectomy or appendectomy) on lrb. Results: 52/718 (7.2%) pts were scored as bleeders: 28/718 (3.9%) G2 and 24/718 (3.3%) G3. n the subgroup of pts previously submitted to SURG (n = 69; 8 G2-G3 lrb), the % volume of rectum receiving more than 70 Gy (V70Gy) was found to be highly correlated with lrb (continuous variable, OR = 1.10,p = 0.012) while V70Gy was of minor importance in the population of pts who did not undergo SURG prior to RT (OR = 1.011, p = 0.09). ROC curves using V70Gy as classifying criterion suggest that V70Gy is a useful constraint for SURG pts (cut-off V70Gy=20%). When considering the kind of surgery, cholecystectomy was found to be highly correlated with lrb (univariate analysis): OR = 4.3 and p = 0.006 when G2-G3 lrb is considered and OR = 5.4 and p = 0.01 when focusing on G3 lrb. Considering MVA (including dosimetric and clinical factors), G2-G3 lrb was significantly correlated to appendectomy (OR = 2.5, p = 0.13), cholecystectomy (OR = 6.1, p = 0.002), androgen deprivation (protective factor, OR = 0.57, p = 0.09) and V75Gy (continuous variable, OR = 1.063, p = 0.004). G3 lrb was mainly correlated to appendectomy (OR = 5.2, p = 0.07) and cholecystectomy (OR = 4.2, p = 0.038).
International Journal of Radiation Oncology*Biology*Physics, 2005
receiving HDR ϩ IMRT. Preliminary results with HDR monotherapy compare favorably to EBRT, LDR Ϯ E... more receiving HDR ϩ IMRT. Preliminary results with HDR monotherapy compare favorably to EBRT, LDR Ϯ EBRT, and HDR ϩ IMRT, both with regard to PSA disease free survival, and complications. With regard to implant technique, HDR brachytherapy offers other advantages over LDR, such as no radiation exposure to hospital personnel, no seed migration, greater dose flexibility and precision of radiation dose delivery. Larger volumes can be treated with HDR. By omitting EBRT, rectal complications may be reduced.