Prognostic significance of neutrophil-to-lymphocyte ratio in HPV status era for oropharyngeal cancer.

AIM: To evaluate the role of baseline neutrophil-to-lymphocyte ratio (NLR) as prognostic marker in squamous cell carcinoma of the oropharynx (OPC) treated with definitive chemoradiotherapy (CRT) in the era of HPV status. PATIENTS AND METHODS: A retrospective analysis of 125 patients (pts) affected with locally advanced OPC was performed. Inclusion criteria were age >18 years, stage III or IV (TNM 7th ed.) and definitive CRT. Haematological marker for their independent role as prognostic biomarkers for progression-free survival (PFS) and overall survival (OS). Logistic models were used to assess the association with downstage in TNM 8th ed. RESULTS: Seventy-seven (61.6%) pts had HPV/p16 + related OPC. Therapeutic choice consisted in sequential and concurrent CRT. Median follow-up was 50 months. A value of NLR ≥3 was associated with poorer OS. Two-year OS was 91% and 81% in pts with NLR <3 and ≥3, respectively. CONCLUSION: A baseline NLR ≥ 3 at treatment initiation represented a negative prognostic marker for OPC treated with definitive CRT. These results are in line with literature data, and prognostic value of NLR has been confirmed restaging our cohort with new TNM staging (8th ed.). Therefore, NLR could be considered a valuable biomarker for risk stratification in pts with OPC.

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

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

HALFMOON TomoTherapy (Helical ALtered Fractionation for iMplant partial OmissiON): implant-sparing post-mastectomy radiotherapy reshaping the clinical target volume in the reconstructed breast.

PURPOSE: To report the dosimetric feasibility of the radiation technique HALFMOON (Helical ALtered Fractionation for iMplant partial OmissiON) for post-mastectomy radiation therapy (PMRT) in intermediate-high-risk breast cancer patients with implant-based immediate breast reconstruction, where the clinical target volume (CTV) does not include the whole implant (implant-sparing approach). METHODS: In the HALFMOON technique, the CTV consisted of skin, subcutaneous tissues, and pectoralis major muscle, excluding the implant, chest wall muscles, and rib plane. The HALFMOON plans were compared with conventionally contoured CTV plans, in which the whole implant, chest wall muscles, and ribs plane were included in the CTV, in a ratio 1:3. All patients underwent hypofractionated treatment of 40.05 Gy/15 fractions, using helical Tomotherapy®. RESULTS: Eighteen patients undergoing HALFMOON technique were compared to 54 subjects treated with conventionally contoured CTV plans. No difference was found in the planning target volume coverage between the two groups. Conversely, a statistically relevant dose reduction in HALFMOON patients was observed for ipsilateral lung (D15%, p < 0.0001; D20%, p < 0.0001; D35%, p = 0.003), contralateral lung (D20%, p = 0.048), contralateral breast (D15%, p = 0.031; D20%, p = 0.047), and stomach (Dmean, p = 0.011). Regarding the implant, V90% and D50% decreased by 46% and 8%, respectively, in the HALFMOON plans (p < 0.0001). CONCLUSION: The HALFMOON approach is technically feasible and resulted in high-dose conformity of the target with a significant reduction of radiation dose delivered to implant and other organs. A clinical study is needed to assess the impact on reconstruction cosmetic outcome and local control.

High precision radiotherapy including intensity-modulated radiation therapy and pulsed-dose-rate brachytherapy for cervical cancer: a retrospective monoinstitutional study.

PURPOSE: To analyse the survival outcomes and toxicity profile of patients treated with pulsed-dose-rate (PDR) brachytherapy (BT) after intensity-modulated radiation therapy (IMRT) for uterine cervical cancer in a single institution. MATERIAL AND METHODS: Between March 2011 and December 2014, 50 patients with histologically proven stages IB1-IVB cervical cancer were treated with IMRT followed by PDR-BT boost. Radiation treatment consisted of IMRT to pelvic with or without paraaortic lymph nodes to a total dose of 45-50.4 Gy. Weekly concomitant chemotherapy was administered to 45 patients. PDR-BT boost was delivered with a median dose of 30 Gy to the high-risk clinical target volume (HR-CTV) after a median time of 14 days since IMRT. Acute and late toxicity were evaluated by Radiation Therapy Oncology Group (RTOG) - European Organization for Research and Treatment of Cancer (EORTC) scoring criteria and Subjective Objective Management Analytic-Late Effects of Normal Tissues (SOMA-LENT) criteria. RESULTS: Two patients had tumour persistence at 6 months after the end of BT. After a median follow-up of 33 months, 6 distant metastases with or without regional relapse were observed. The 1- and 5-year progression-free survival was 83% (95% CI: 69-91%) and 76% (95% CI: 61-86%), whereas the 3- and 5-year overall survival was 91% (95% CI: 78-97%) and 76% (95% CI: 56-88%), respectively. Urinary and rectal toxicity higher than grade 2 was observed in 6.3% and 17% of patients, respectively. Five patients (10.6%) had grade 4 gastrointestinal toxicity requiring colostomy. CONCLUSIONS: Our study confirms that the combination of IMRT and PDR-BT can be considered an effective treatment for cervical cancer, ensuring high local control, despite the high percentage of locally advanced disease.

Evaluation of target coverage and margins adequacy during CyberKnife Lung Optimized Treatment.

PURPOSE: Evaluation of target coverage and verification of safety margins, in motion management strategies implemented by Lung Optimized Treatment (LOT) module in CyberKnife system. METHODS: Three fiducial-less motion management strategies provided by LOT can be selected according to tumor visibility in the X ray images acquired during treatment. In 2-view modality the tumor is visible in both X ray images and full motion tracking is performed. In 1-view modality the tumor is visible in a single X ray image, therefore, motion tracking is combined with an internal target volume (ITV)-based margin expansion. In 0-view modality the lesion is not visible, consequently the treatment relies entirely on an ITV-based approach. Data from 30 patients treated in 2-view modality were selected providing information on the three-dimensional tumor motion in correspondence to each X ray image. Treatments in 1-view and 0-view modalities were simulated by processing log files and planning volumes. Planning target volume (PTV) margins were defined according to the tracking modality: end-exhale clinical target volume (CTV) + 3 mm in 2-view and ITV + 5 mm in 0-view. In the 1-view scenario, the ITV encompasses only tumor motion along the non-visible direction. Then, non-uniform ITV to PTV margins were applied: 3 mm and 5 mm in the visible and non-visible direction, respectively. We defined the coverage of each voxel of the CTV as the percentage of X ray images where such voxel was included in the PTV. In 2-view modality coverage was calculated as the intersection between the CTV centred on the imaged target position and the PTV centred on the predicted target position, as recorded in log files. In 1-view modality, coverage was calculated as the intersection between the CTV centred on the imaged target position and the PTV centred on the projected predictor data. In 0-view modality coverage was calculated as the intersection between the CTV centred on the imaged target position and the non-moving PTV. Similar to dose-volume histogram, CTV coverage-volume histograms (defined as CVH) were derived for each patient and treatment modality. The geometric coverages of the 90% and 95% of CTV volume (C90, C95, respectively) were evaluated. Patient-specific optimal margins (ensuring C95 ≥ 95%) were computed retrospectively. RESULTS: The median ± interquartile-rage of C90 and C95 for upper lobe lesions was 99.1 ± 0.6% and 99.0 ± 3.1%, whereas they were 98.9 ± 4.2% and 97.8 ± 7.5% for lower and middle lobe tumors. In 2-view, 1-view and 0-view modality, adopted margins ensured C95 ≥ 95% in 70%, 85% and 63% of cases and C95 ≥ 90% in 90%, 88% and 83% of cases, respectively. In 2-view, 1-view and 0-view a reduction in margins still ensured C95 ≥ 95% in 33%, 78% and 59% of cases, respectively. CONCLUSIONS: CTV coverage analysis provided an a-posteriori evaluation of the treatment geometric accuracy and allowed a quantitative verification of the adequacy of the PTV margins applied in CyberKnife LOT treatments offering guidance in the selection of CTV margins.

Salvage Stereotactic Body Radiotherapy for Isolated Lymph Node Recurrent Prostate Cancer: Single Institution Series of 94 Consecutive Patients and 124 Lymph Nodes.

BACKGROUND: The purpose of the study was to evaluate the prostate serum antigen (PSA) response, local control, progression-free survival (PFS), and toxicity of stereotactic body radiotherapy (SBRT) for lymph node (LN) oligorecurrent prostate cancer. PATIENTS AND METHODS: Between May 2012 and October 2015, 124 lesions were treated in 94 patients with a median dose of 24 Gy in 3 fractions. Seventy patients were treated for a single lesion and 25 for > 1 lesion. In 34 patients androgen deprivation (AD) was combined with SBRT. We evaluated biochemical response according to PSA level every 3 months after SBRT: a 3-month PSA decrease from pre-SBRT PSA of more than 10% identified responder patients. In case of PSA level increase, imaging was performed to evaluate clinical progression. Toxicity was assessed every 6 to 9 months after SBRT. RESULTS: Median follow-up was 18.5 months. In 13 patients (14%) Grade 1 to 2 toxicity was reported without any Grade 3 to 4 toxicity. Biochemical response, stabilization, and progression were observed in 64 (68%), 10 (11%), and 20 (21%) of 94 evaluable patients. Clinical progression was observed in 31 patients (33%) after a median time of 8.1 months. In-field progression occurred in 12 lesions (9.7%). Two-year local control and PFS rates were 84% and 30%, respectively. Age older than 75 years correlated with better biochemical response rate. Age older than 75 years, concomitant AD administered up to 12 months, and pelvic LN involvement correlated with longer PFS. CONCLUSION: SBRT is safe and offers good in-field control. At 2 years after SBRT, 1 of 3 patients is progression-free. Further investigation is warranted to identify patients who benefit most from SBRT and to define the optimal combination with AD.