Radiosurgery and fractionated stereotactic body radiotherapy for patients with lung oligometastases

Background: Patients with oligometastatic disease can potentially be cured by using an ablative therapy for all active lesions. Stereotactic body radiotherapy (SBRT) is a non-invasive treatment option that lately proved to be as effective and safe as surgery in treating lung metastases (LM). However, it is not clear which patients benefit most and what are the most suitable fractionation regimens. The aim of this study was to analyze treatment outcomes after single fraction radiosurgery (SFRS) and fractionated SBRT (fSBRT) in patients with lung oligometastases and identify prognostic clinical features for better survival outcomes. Methods: Fifty-two patients with 94 LM treated with SFRS or fSBRT between 2010 and 2016 were analyzed. The characteristics of primary tumor, LM, treatment, toxicity profiles and outcomes were assessed. Kaplan-Meier and Cox regression analyses were used for estimation of local control (LC), overall survival (OS) and progression-free survival. Results: Ninety-four LM in 52 patients were treated using SFRS/fSBRT with a median of 2 lesions per patient (range: 1-5). The median planning target volume (PTV)-encompassing dose for SFRS was 24 Gy (range: 17-26) compared to 45 Gy (range: 20-60) in 2-12 fractions with fSBRT. The median follow-up time was 21 months (range: 3-68). LC rates at 1 and 2 years for SFSR vs. fSBRT were 89 and 83% vs. 75 and 59%, respectively (p = 0.026). LM treated with SFSR were significantly smaller (p = 0.001). The 1 and 2-year OS rates for all patients were 84 and 71%, respectively. In univariate analysis treatment with SFRS, an interval of ≥12 months between diagnosis of LM and treatment, non-colorectal cancer histology and BED 70% and time to first metastasis ≥12 months. There was no grade 3 acute or late toxicity. Conclusions: Longer time to first metastasis, good KPS and N0 predicted better OS. Good LC and low toxicity rates were achieved after short SBRT schedules

A non-randomised, single-centre comparison of induction chemotherapy followed by radiochemotherapy versus concomitant chemotherapy with hyperfractionated radiotherapy in inoperable head and neck carcinomas

BACKGROUND: The application of induction chemotherapy failed to provide a consistent benefit for local control in primary treatment of advanced head and neck (H&N) cancers. The aim of this study was to compare the results of concomitant application of radiochemotherapy for treating locally advanced head-and-neck carcinoma in comparison with the former standard of sequential radiochemotherapy. METHODS: Between 1987 and 1995 we treated 122 patients with unresectable (stage IV head and neck) cancer by two different protocols. The sequential protocol (SEQ; 1987–1992) started with two courses of neoadjuvant chemotherapy (cisplatin [CDDP] + 120-h continuous infusions (c.i.) of folinic acid [FA] and 5-fluorouracil [5-FU]), followed by a course of radiochemotherapy using conventional fractionation up to 70 Gy. The concomitant protocol (CON; since 1993) combined two courses of FA/5-FU c.i. plus mitomycin (MMC) concomitantly with a course of radiotherapy up to 30 Gy in conventional fractionation, followed by a hyperfractionated course up to 72 Gy. Results from the two groups were compared. RESULTS: Patient and tumor characteristics were balanced (SEQ = 70, CON = 52 pts.). Mean radiation dose achieved (65.3 Gy vs. 71.6 Gy, p = 0.00), response rates (67 vs. 90 % for primary, p = 0.02), and local control (LC; 17.6% vs. 41%, p = 0.03), were significantly lower in the SEQ group, revealing a trend towards lower disease-specific (DSS; 19.8% vs. 31.4%, p = 0.08) and overall (14.7% vs. 23.7%, p = 0.11) survival rates after 5 years. Mucositis grades III and IV prevailed in the CON group (54% versus 44%). Late toxicity was similar in both groups. CONCLUSION: Concurrent chemotherapy seemed more effective in treating head and neck tumors than induction chemotherapy followed by chemoradiation, resulting in better local control and a trend towards improved survival

Intensity-Modulated Radiotherapy in Patients with Cervical Cancer. An intra-individual Comparison of Prone and Supine Positioning

<p>Abstract</p> <p>Background</p> <p>Chemoradiation for cervical cancer patients is associated with considerable gastrointestinal toxicity. Intensity-modulated radiotherapy (IMRT) has demonstrated superiority in terms of target coverage and normal tissue sparing in comparison to conventional 3D planning in gynaecological malignancies. Whether IMRT in prone (PP) or supine position (SP) might be beneficial for cervical cancer patients remains partially unanswered.</p> <p>Methods</p> <p>10 patients on FIGO stage IB-III cervical cancer, 6 patients for definitive and 4 patients for adjuvant external beam pelvic RT, were planned in PP and SP using a 7-field IMRT technique. IMRT plans for PP and SP (mean dose, D_mean50.4 Gy) were optimized in terms of PTV coverage (1^stpriority) and small bowel sparing (2^ndpriority). A comparison of DVH parameters for PTV, small bowel, bladder, and rectum was performed.</p> <p>Results</p> <p>The comparison showed a similar PTV coverage of 95% of the prescribed dose and for target conformity in IMRT plans (PP, SP). PTV, rectum and bladder volumes were comparable for PP and SP. Significantly larger volumes of small bowel were found in PP (436 cc, + 35%, p = 0.01). PP decreased the volume of small bowel at 20-50.4 Gy (p < 0.05) and increased the rectum volumes covered by doses from 10-40 Gy (p < 0.01), the V50.4 was < 5% in both treatment positions. Bladder sparing was significant better at 50.4 Gy (p = 0.03) for PP.</p> <p>Conclusion</p> <p>In this dosimetric study, we demonstrated that pelvic IMRT in prone position for patients with cervical cancer seems to be beneficial in reducing small bowel volume at doses ≥20 Gy while providing similar target coverage and target conformity. The use of frequent image guidance with KV (kilovolt) or MV (megavolt) computertomography can reduce set-up deviations, and treatment in prone position can be done with a higher set-up accuracy. Clinical outcome studies are needed to affirm lower toxicity.</p

Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group

Background and purposeThe Meta-Analysis of Chemotherapy in squamous cell Head and Neck Cancer (MACH-NC) demonstrated that concomitant chemotherapy (CT) improved overall survival (OS) in patients without distant metastasis. We report the updated results.Materials and methodsPublished or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT&nbsp;+&nbsp;CT or adding another timing of CT to LRT&nbsp;+&nbsp;CT (main question), or comparing induction CT&nbsp;+&nbsp;radiotherapy to radiotherapy&nbsp;+&nbsp;concomitant (or alternating) CT (secondary question) were eligible. Individual patient data were collected and combined using a fixed-effect model. OS was the main endpoint.ResultsFor the main question, 101 trials (18951 patients, median follow-up of 6.5&nbsp;years) were analyzed. For both questions, there were 16 new (2767 patients) and 11 updated trials. Around 90% of the patients had stage III or IV disease. Interaction between treatment effect on OS and the timing of CT was significant (p&nbsp;&lt;&nbsp;0.0001), the benefit being limited to concomitant CT (HR: 0.83, 95%CI [0.79; 0.86]; 5(10)-year absolute benefit of 6.5% (3.6%)). Efficacy decreased as patients age increased (p_trend&nbsp;=&nbsp;0.03). OS was not increased by the addition of induction (HR&nbsp;=&nbsp;0.96 [0.90; 1.01]) or adjuvant CT (1.02 [0.92; 1.13]). Efficacy of induction CT decreased with poorer performance status (p_trend&nbsp;=&nbsp;0.03). For the secondary question, eight trials (1214 patients) confirmed the superiority of concomitant CT on OS (HR&nbsp;=&nbsp;0.84 [0.74; 0.95], p&nbsp;=&nbsp;0.005).ConclusionThe update of MACH-NC confirms the benefit and superiority of the addition of concomitant CT for non-metastatic head and neck cancer