A multicenter LArge retrospectIve daTabase on the personalization of stereotactic ABlative radiotherapy use in lung metastases from colon-rectal cancer: The LaIT-SABR study.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic disease, but local control of colorectal metastases remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate the progression to the polymetastatic disease (PMD). MATERIAL AND METHODS: The study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1033 lung metastases were reported. Clinical and biological parameters were evaluated as predictive for freedom from local progression-free survival (FLP). Secondary end-point was the time to the polymetastatic conversion (tPMC). RESULTS: Two-year FLP was 75.4%. Two-year FLP for lesions treated with a BED < 00 Gy, 100-124 Gy, and ≥125 Gy was 76.1%, 70.6%, and 94% (p = 0.000). Two-year FLP for lesion measuring ≤10 mm, 10-20 mm, and >20 mm was 79.7%, 77.1%, and 66.6% (p = 0.027). At the multivariate analysis a BED ≥125 Gy significantly reduced the risk of local progression (HR 0.24, 95%CI 0.11-0.51; p = 0.000). Median tPMC was 26.8 months. Lesions treated with BED ≥125 Gy reported a significantly longer tPMC as compared to lower BED. The median tPMC for patients treated to 1, 2-3 or 4-5 simultaneous oligometastases was 28.5, 25.4, and 9.8 months (p = 0.035). CONCLUSION: The present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Predictive factors were identified for treatment personalization.

Acute and intermediate toxicity of 3-week radiotherapy with simultaneous integrated boost using TomoDirect: prospective series of 287 early breast cancer patients

Aims To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality. Methods Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria. Results The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13–3.63) and 1.84 (1.26–2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good–excellent result for 86% of patients (AU)

Acute and intermediate toxicity of 3-week radiotherapy with simultaneous integrated boost using TomoDirect: prospective series of 287 early breast cancer patients.

AIMS: To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality. METHODS: Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria. RESULTS: The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13-3.63) and 1.84 (1.26-2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good-excellent result for 86% of patients. CONCLUSIONS: Hypofractionated WB IMRT with a SIB to the TB, delivered with TomoDirect modality, is safe and well-tolerated. Most patients reported no toxicity after 6 months and good-excellent cosmesis. Predictive factors of clinically relevant toxicity might be considered during treatment planning in order to further reduce side effects.

Radiation-induced acute dysphagia : Prospective observational study on 42 head and neck cancer patients.

PURPOSE: Acute toxicity in head and neck (H&N) cancer patients treated with definitive radiotherapy (RT) has a crucial role in compliance to treatments. The aim of this study was to correlate doses to swallowing-associated structures and acute dysphagia. METHODS: We prospectively analyzed 42 H&N cancer patients treated with RT. Dysphagia (grade ≥ 3) and indication for percutaneous endoscopic gastrostomy (PEG) insertion were classified as acute toxicity. Ten swallowing-related structures were considered for the dosimetric analysis. The correlation between clinical information and the dose absorbed by the contoured structures was analyzed. Multivariate logistic regression method using resampling methods (bootstrapping) was applied to select model order and parameters for normal tissue complication probability (NTCP) modelling. RESULTS: A strong multiple correlation between dosimetric parameters was found. A two-variable model was suggested as the optimal order by bootstrap method. The optimal model (Rs = 0.452, p < 0.001) includes V45 of the cervical esophagus (odds ratio [OR] = 1.016) and Dmean of the cricopharyngeal muscle (OR = 1.057). The model area under the curve was 0.82 (95% confidence interval 0.69-0.95). CONCLUSION: Our results suggested that the absorbed dose to the cricopharyngeal muscle and cervical esophagus might play a relevant role in the development of acute RT-related dysphagia.

VERO® radiotherapy for low burden cancer: 789 patients with 957 lesions.

PURPOSE: The aim of this retrospective study is to evaluate patient profile, feasibility, and acute toxicity of RadioTherapy (RT) delivered by VERO® in the first 20 months of clinical activity. METHODS: Inclusion criteria: 1) adult patients; 2) limited volume cancer (M0 or oligometastatic); 3) small extracranial lesions; 4) treatment between April 2012 and December 2013 and 5) written informed consent. Two techniques were employed: intensity modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT). Toxicity was evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) criteria. RESULTS: Between April 2012 and December 2013, 789 consecutive patients (957 lesions) were treated. In 84% of them one lesion was treated and in 16% more than one lesion were treated synchronously/metachronously; first radiotherapy course in 85%, re-irradiation in 13%, and boost in 2% of cases. The treated region included pelvis 46%, thorax 38%, upper abdomen 15%, and neck 1%. Radiotherapy schedules included <5 and >5 fractions in 75% and 25% respectively. All patients completed the planned treatment and an acceptable acute toxicity was observed. CONCLUSIONS: RT delivered by VERO® was administrated predominantly to thoracic and pelvic lesions (lung and urologic tumours) using hypofractionation. It is a feasible approach for limited burden cancer offering short and well accepted treatment with favourable acute toxicity profile. Further investigation including dose escalation and other available VERO® functionalities such as real-time dynamic tumour tracking is warranted in order to fully evaluate this innovative radiotherapy system.

Salvage image-guided intensity modulated or stereotactic body reirradiation of local recurrence of prostate cancer.

OBJECTIVE: To retrospectively evaluate external beam reirradiation (re-EBRT) delivered to the prostate/prostatic bed for local recurrence, after radical or adjuvant/salvage radiotherapy (RT). METHODS: 32 patients received re-EBRT between February 2008 and October 2013. All patients had clinical/radiological local relapse in the prostate or prostatic bed and no distant metastasis. re-EBRT was delivered with selective RT technologies [stereotactic RT including CyberKnife(TM) (Accuray, Sunnyvale, CA); image-guidance and intensity-modulated RT etc.]. Toxicity was evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Biochemical control was assessed according to the Phoenix definition (NADIR + 2 ng ml(-1)). RESULTS: Acute urinary toxicity: G0, 24 patients; G1, 6 patients; G2, 2 patients. Acute rectal toxicity: G0, 28 patients; G1, 2 patients; and G2, 1 patient. Late urinary toxicity (evaluated in 30 cases): G0, 23 patients; G1, 6 patients; G2, 1 patient. Late renal toxicity: G0, 25 patients; G1, 5 patients. A mean follow-up of 21.3 months after re-EBRT showed that 13 patients were free of cancer, 3 were alive with biochemical relapse and 12 patients were alive with clinically evident disease. Four patients had died: two of disease progression and two of other causes. CONCLUSION: re-EBRT using modern technology is a feasible approach for local prostate cancer recurrence offering 2-year tumour control in about half of the patients. Toxicity of re-EBRT is low. Future studies are needed to identify the patients who would benefit most from this treatment. ADVANCES IN KNOWLEDGE: Our series, based on experience in one hospital alone, shows that re-EBRT for local relapse of prostate cancer is feasible and offers a 2-year cure in about half of the patients.

Two controlled evaluations of multicomponent psychological treatment of irritable bowel syndrome.

We report two controlled comparisons of a previously validated multicomponent (relaxation, thermal biofeedback, and cognitive therapy) treatment for irritable bowel syndrome (IBS) to an ostensible attention-placebo control (pseudo-meditation and EEG alpha suppression biofeedback) and to a symptom-monitoring control. In Study 1 (n = 10 per condition) there were nonsignificant trends for the multicomponent treatment to be superior to the attention-placebo condition. In Study 2 (n = 30 per condition), we found no advantage for the multicomponent treatment over the attention-placebo condition. Subjects in both treatment conditions showed significant reductions in GI symptoms, as measured by daily symptom diaries, and significant reductions in trait anxiety and depression. The GI symptom reductions held up over a 6 month follow-up. Possible explanations for the results are explored.

The USA-USSR collaborative cross-cultural comparison of autogenic training and thermal biofeedback in the treatment of mild hypertension.

We have conducted a cross-cultural (USA and USSR) comparison of thermal biofeedback (TBF) and autogenic training (AT) to a self-relaxation control condition in 59 unmedicated males with mild hypertension. Identical assessment and treatment protocols were carried out in both settings (Albany, New York, and Moscow). Treatments were delivered in small groups on an outpatient basis twice per week for 10 weeks. Results showed comparable, significant (p less than .05), short-term decreases (M = 8.5 mm Hg) in diastolic blood pressure (DBP) for both treatments at both sites. However, the Soviet patients, starting with significantly (p less than .01) higher systolic blood pressures (SBPs), showed significant decreases (M = 12.8 mm Hg) in SBP, whereas the American patients did not change appreciably (M = 4.6 mm Hg). During follow-up, the treated Soviet patients showed significantly (p less than .05) better maintenance of treatment effects, from 3 months to 1 year, than did the American patients. At 1 year, 75% of the treated Soviet patients had DBPs less than 90 mm Hg, whereas only 24% of the American patients had comparable DBPs.

A controlled comparison of thermal biofeedback and relaxation training in the treatment of essential hypertension: III. Psychological changes accompanying treatment.

Eighty-seven medicated essential hypertensives received either thermal biofeedback (TBF) or progressive muscle relaxation (PMR) training as a substitute for their second-stage antihypertensive medication. The psychological changes accompanying the treatments were obtained at pretreatment, at post-treatment and at the 3- and 6-month follow-up. Few psychological changes were noted, owing in part to the absence of psychopathological elevations at pretreatment. Short-term psychological changes were greater in patients who were withdrawn from their second-stage antihypertensive medication and then treated compared with those treated and then withdrawn from their medication. This finding may reflect the presence of antihypertensive medication side effects involving psychological factors. In general, TBF patients were more Type B at long-term follow-up compared with PMR patients, who tended toward greater Type A characteristics.

Evaluation of a minimal-therapist-contact thermal biofeedback treatment program for essential hypertension.

We compared a clinic-based regimen of 16 individual sessions (2 per week) of thermal biofeedback with a largely home-based regimen of 5 sessions (spread over 8 weeks) for the treatment of essential hypertension in patients who required at least two drugs to maintain control of blood pressure (BP). On the basis of the clinical end point of being successfully withdrawn from the second stage medication while BP remained under control, the clinic-based regimen (5 of 9) was superior (chi less than (1) = 4.0, p less than .05) to the home-based regimen (1 of 9). Internal analyses point to more frequently obtaining a hand temperature of at least 95 degrees F by the office-based patients as possibly the reason for the difference.

Psychological changes associated with self-regulatory treatments of irritable bowel syndrome.

The psychological "side effects" of self-regulatory treatment (a combination of relaxation, thermal biofeedback, and cognitive therapy) for irritable bowel syndrome (IBS) were compared among 20 "successfully" treated patients, 12 "unsuccessfully" treated patients, and 9 patients who merely monitored symptoms for 12 weeks. Pretreatment and posttreatment scores on the Beck Depression Inventory, State-Trait Anxiety Inventory, and Psychosomatic Symptom Checklist were examined. "Successfully" treated patients had significant (p less than .01) reductions on all measures and significantly greater reductions on depression and state anxiety than the symptom monitoring group. Interestingly, the failures also showed a significant (p = .027) reduction in trait anxiety and no significant increases on other measures.

Psychological comparisons of irritable bowel syndrome to chronic tension and migraine headache and nonpatient controls.

Comparisons were made among patients with IBS (n = 55), tension headache (n = 69), or migraine headache (n = 68) and nonpatient controls (n = 64) on the MMPI and several other psychological tests, including BDI, STAI, Life Events, and Psychosomatic Symptom Checklist. With two nonsignificant exceptions (MMPI scale F and Life Events) the groups were consistently ordered, in terms of increasing psychological distress: Normals less than Migraine Headache less than Tension Headache less than IBS. The IBS patients were more like the tension headache patients than any other group. Subgroups of IBS patients, on the basis of presence or absence of diarrhea or constipation in addition to abdominal pain, were generally not significantly different on the psychological tests.