Dosimetric comparison of stereotactic MR-guided radiation therapy (SMART) and HDR brachytherapy boost in cervical cancer.

PURPOSE: The standard of care in locally advanced cervical cancer (LACC) is concomitant chemoradiotherapy followed by high-dose-rate brachytherapy (HDR-BT). Although previous studies compared HDR-BT with stereotactic body radiotherapy (SBRT), there is scarce data regarding the dosimetric outcomes of stereotactic MR-guided adaptive radiation therapy (SMART) boost in lieu of HDR-BT. METHODS AND MATERIALS: In this single-institutional in-silico comparative study, LACC patients who were definitively treated with external beam radiotherapy followed by HDR-BT were selected. Target volumes and organs at risk (OARs) were delineated in MRI and HDR-planning CT. An HDR-BT and a SMART boost plan were generated with a prescribed dose of 28 Gy in four fractions for all patients. The HDR-BT and SMART boost plans were compared in regard to target coverage as well OARs doses. RESULTS: Mean EQD2 D90 to HR-CTV and IR-CTV for HDR-BT plans were 89.7 and 70.5 Gy, respectively. For SMART, the mean EQD2 D90 to HR-PTV, HR-CTV, and IR-CTV were 82.9, 95.4, and 70.2 Gy, respectively. The mean D2cc EQD2 of bladder, rectum, and sigmoid colon for HDR-BT plans were 86.4, 70.7, and 65.7 Gy, respectively. The mean D2cc EQD2 of bladder, rectum, and sigmoid colon for SMART plans were 81.4, 70.8, and 73.6 Gy, respectively. All dose constraints in terms of target coverage and OARs constraints were met for both HDR-BT and SMART plans. CONCLUSIONS: This dosimetric study demonstrates that SMART can be applied in cases where HDR-BT is not available or ineligible with acceptable target coverage and OAR sparing. However, prospective clinical studies are needed to validate these results.

The effect of P53 expression and smoking/alcohol in P16(+) and P16(-) oropharyngeal carcinoma and risk classification: the Turkish Society of Radiation Oncology Head & Neck Study Group 01-002.

OBJECTIVE: The aim of this study is to categorize the risk groups of patients with oropharyngeal carcinoma (OPC) according to p16 and p53 status, smoking/alcohol consumption history, and other prognostic factors. STUDY DESIGN: The immunostaining of p16 and p53 of 290 patients was retrospectively evaluated. The history of smoking/alcohol consumption of each patient was noted. p16 and p53 staining patterns were reviewed. The results were compared with demographic findings and prognostic factors. Risk groups have been classified for the p16 status of patients. RESULTS: The median follow-up was 47 months (range 6-240). Five-year disease-free survival (DFS) rates for patients with p16 (+) and (-) were 76% and 36%, and overall survival rates were 83% vs 40%, respectively (HR = 0.34 [0.21-0.57], P < .0001), HR = 0.22 [0.12-0.40] P < .0001, respectively). p16(-), p53(+), heavy smoking/alcohol consumption, performance status; advanced T and N stages in patients with p16(-), and continuing smoking/alcohol consumption after treatment were found to be unfavorable risk factors. Five-year overall survival rates were 95%, 78%, and 36% for low, intermediate, and high-risk groups, respectively. CONCLUSIONS: The results of our study have shown that p16 negativity in patients with oropharyngeal cancer was found to be an important prognostic factor, especially for those with lower p53 expression and not smoking/consuming alcohol.

A multicenter retrospective analysis of patients with nasopharyngeal carcinoma treated in IMRT era from a nonendemic population: Turkish Society for Radiation Oncology Head and Neck Cancer Group Study (TROD 01-001).

BACKGROUND: We aimed to evaluate patients with nasopharyngeal carcinoma (NPC) in a nonendemic population. METHODS: In a national, retrospective, multicenteric study, 563 patients treated with intensity modulated radiotherapy at 22 centers between 2015 and 2020 were analyzed. RESULTS: Median age was 48 (9-83), age distribution was bimodal, 74.1% were male, and 78.7% were stage III-IVA. Keratinizing and undifferentiated carcinoma rates were 3.9% and 81.2%. Patients were treated with concomitant chemoradiotherapy (48.9%), or radiotherapy combined with induction chemotherapy (25%) or adjuvant chemotherapy (19.5%). After 34 (6-78) months follow-up, 8.2% locoregional and 8% distant relapse were observed. Three-year overall survival was 89.5% and was lower in patients with age ≥50, male sex, keratinizing histology, T4, N3 and advanced stage (III-IVA). CONCLUSIONS: Patients with NPC in Turkey have mixed clinical features of both east and west. Survival outcomes are comparable to other reported series; however, the rate of distant metastases seems to be lower.

Robotic male and laparoscopic female sphincter-preserving total mesorectal excision of mid-low rectal cancer share similar specimen quality, complication rates and long-term oncological outcomes.

The aim of this study was to compare perioperative and long-term oncological outcomes between laparoscopic sphincter-preserving total mesorectal excision in female patients (F-Lap-TME) and robotic sphincter-preserving total mesorectal excision in male patients (M-Rob-TME) with mid-low rectal cancer (RC). A retrospective analysis of a prospectively maintained database was performed. 170 cases (F-Lap-TME: 60 patients; M-Rob-TME: 110 patients) were performed by a single surgeon (January 2011-January 2020). Clinical characteristics did not differ significantly between the two groups. Operating time was longer in M-Rob-TME than in F-Lap-TME group (185.3 ± 28.4 vs 124.5 ± 35.8 min, p < 0.001). There was no conversion to open surgery in both groups. Quality of mesorectum was complete/near-complete in 58 (96.7%) and 107 (97.3%) patients of F-Lap-TME and M-Rob-TME (p = 0.508), respectively. Circumferential radial margin involvement was observed in 2 (3.3%) and 3 (2.9%) in F-Lap-TME and M-Rob-TME patients (p = 0.210), respectively. Median length of follow-up was 62 (24-108) months in the F-Lap-TME and 64 (24-108) months in the M-Rob-TME group. Five-year overall survival rates were 90.5% in the F-Lap-TME and 89.6% in the M-Rob-TME groups (p = 0.120). Disease-free survival rates in F-Lap-TME and M-Rob-TME groups were 87.5% and 86.5% (p = 0.145), respectively. Local recurrence rates were 5% (n = 3) and 5.5% (n = 6) (p = 0.210), in the F-Lap-TME and M-Rob-TME groups, respectively. The robotic technique can potentially overcome some technical challenges related to the pelvic anatomical difference between sex compared to laparoscopy. Laparoscopic and robotic approach, respectively in female and male patients provide similar surgical specimen quality, perioperative outcomes, and long-term oncological results.

Outcomes of carotid sparing intensity-modulated radiotherapy for early stage glottic cancer in 201 patients: Multicenter study of Turkish Radiation Oncology Society/TROD-01-007.

BACKGROUND: To assess and report clinical outcomes after carotid sparing intensity-modulated radiotherapy for early stage laryngeal cancer. METHODS: We retrospectively analyzed 201 patients with early stage glottic laryngeal cancer treated with carotid sparing intensity-modulated radiotherapy (IMRT)/volumetric modulated arc therapy (VMAT) techniques in six TROD centers. RESULTS: After a median follow-up of 31 months the actuarial 1- and 3-year local and locoregional control rates were 99.4% and 94.7%, 98.4% and 93%, respectively. T classification, anterior commissure involvement, IMRT technique, and type of fractionation were not found to be prognostic for local control. Overall, eight patients had lost their organ function due to recurrence or toxicity. Grade 3 and 4 acute laryngeal edema was seen in eight (4%) and one (0.5%) of patients, respectively. Grade 3 and 4 late laryngeal edema developed in two (1%) and one patient (0.5%), respectively. CONCLUSION: Oncologic outcomes of patients treated with carotid sparing IMRT were excellent; comparable with historical series, with acceptable side effects. Longer follow-up is needed to estimate long term effect on stroke.

Watch and Wait Strategy for Rectal Cancer: How Long Should We Wait for a Clinical Complete Response?

BACKGROUND: The objective of this study was to determine how long to wait in locally advanced rectal tumor (LARC) patients who receive total neoadjuvant therapy (TNT) and achieve a clinical complete response (cCR), and to identify the clinical parameters that affect the waiting period for the watch-and-wait strategy (W &W). MATERIALS AND METHODS: The data of patients who achieved cCR between February 2015 and June 2020 were examined retrospectively. The week in which patients with cCR at the end of TNT achieved clearance was determined by reanalyzing recorded endoscopy video images. In the assessment at the time of the initial diagnosis, tumor characteristics, such as digital rectal examination findings, MRI stage, location with respect to the puborectalis muscle, annularity, and tumor size, were recorded prospectively. RESULTS: A total of 54 patients were included in this study. According to the MRI-T stage, 14 cases were cT3a, 22 were cT3b, and 18 were cT3c-T4. Forty-four percent of the cases achieved cCR at 8-10 weeks, 19% at 12-16 weeks, 20% at 16-22 weeks, and 17% at 20-26 weeks. Patients with tumors that were early MRI-T stage (cT3a), negative clinical circumferential resection margin, mobile, small (≤4 cm), located above the puborectalis muscle and showed <180 degrees annularity achieved cCR significantly earlier than those with other tumors (p<0.05). CONCLUSION: In this study, cCR was achieved in less than half (44%) of the cases during the 8-10 week waiting period. In the W&W strategy, the initial assessment for cCR seems insufficient, and we may need to wait up to 26-30 weeks, especially in patients with advanced-stage tumors.

Risk of symptomatic radiation necrosis in patients treated with stereotactic radiosurgery for brain metastases.

INTRODUCTIO: Stereotactic radiosurgery (SRS) is a treatment option in the initial management of patients with brain metastases. While its efficacy has been demonstrated in several prior studies, treatment-related complications, particularly symptomatic radiation necrosis (RN), remains as an obstacle for wider implementation of this treatment modality. We thus examined risk factors associated with the development of symptomatic RN in patients treated with SRS for brain metastases. PATIENTS AND METHODS: We performed a retrospective review of our institutional database to identify patients with brain metastases treated with SRS. Diagnosis of symptomatic RN was determined by appearance on serial MRIs, MR spectroscopy, requirement of therapy, and the development of new neurological complaints without evidence of disease progression. RESULTS: We identified 323 brain metastases treated with SRS in 170 patients from 2009 to 2018. Thirteen patients (4%) experienced symptomatic RN after treatment of 23 (7%) lesions. After SRS, the median time to symptomatic RN was 8.3 months. Patients with symptomatic RN had a larger mean target volume (p<0.0001), and thus larger V100% (p<0.0001), V50% (p<0.0001), V12Gy (p<0.0001), and V10Gy (p=0.0002), compared to the rest of the cohort. Single-fraction treatment (p=0.0025) and diabetes (p=0.019) were also significantly associated with symptomatic RN. CONCLUSION: SRS is an effective treatment option for patients with brain metastases; however, a subset of patients may develop symptomatic RN. We found that patients with larger tumor size, larger plan V100%, V50%, V12Gy, or V10Gy, who received single-fraction SRS, or who had diabetes were all at higher risk of symptomatic RN.

Stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of liver metastases in oligometastatic patients: initial clinical experience.

PURPOSE: We aimed to present our initial clinical experience on the implementation of a stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of liver metastases in oligometastatic disease. MATERIALS AND METHODS: Twenty-one patients (24 lesions) with liver metastasis treated with SMART were included in this retrospective study. Step-and-shoot intensity-modulated radiotherapy technique was used with daily plan adaptation. During delivery, real-time imaging was used by acquiring planar magnetic resonance images in sagittal plane for monitoring and gating. Acute and late toxicities were recorded both during treatment and follow-up visits. RESULTS: The median follow-up time was 11.6 months (range, 2.2 to 24.6 months). The median delivered total dose was 50 Gy (range, 40 to 60 Gy); with a median fraction number of 5 (range, 3 to 8 fractions) and the median fraction dose was 10 Gy (range, 7.5 to 18 Gy). Ninety-three fractions (83.7%) among 111 fractions were re-optimized. No patients were lost to follow-up and all patients were alive except one at the time of analysis. All of the patients had either complete (80.9%) or partial (19.1%) response at irradiated sites. Estimated 1-year overall survival was 93.3%. Intrahepatic and extrahepatic progression-free survival was 89.7% and 73.5% at 1 year, respectively. There was no grade 3 or higher acute or late toxicities experienced during the treatment and follow-up course. CONCLUSION: SMART represents a new, noninvasive and effective alternative to current ablative radiotherapy methods for treatment of liver metastases in oligometastatic disease with the advantages of better visualization of soft tissue, real-time tumor tracking and potentially reduced toxicity to organs at risk.

Time Analysis of Online Adaptive Magnetic Resonance-Guided Radiation Therapy Workflow According to Anatomical Sites.

PURPOSE: To document time analysis of detailed workflow steps for the online adaptive magnetic resonance-guided radiation therapy treatments (MRgRT) with the ViewRay MRIdian system and to identify the barriers to and solutions for shorter treatment times. METHODS AND MATERIALS: A total of 154 patients were treated with the ViewRay MRIdian system between September 2018 and October 2019. The time process of MRgRT workflow steps of 962 fractions for 166 treatment sites was analyzed in terms of patient and online adaptive treatment (ART) characteristics. RESULTS: Overall, 774 of 962 fractions were treated with online ART, and 83.2% of adaptive fractions were completed in less than 60 minutes. Sixty-three percent, 50.3%, and 4.2% of fractions were completed in less than 50 minutes, 45 minutes, and 30 minutes, respectively. Eight-point-three percent and 3% of fractions were completed in more than 70 minutes and 80 minutes, respectively. The median time (tmed) for ART workflow steps were as follows: (1) setup tmed: 5.0 minutes, (2) low-resolution scanning tmed: 1 minute, (3) high-resolution scanning tmed: 3 minutes, (4) online contouring tmed: 9 minutes, (5) reoptimization with online quality assurance tmed: 5 minutes, (6) real targeting tmed: 3 minutes, (7) beam delivery with gating tmed: 17 minutes, and (8) net total treatment time tmed: 45 minutes. The shortest and longest tmean rates of net total treatment time were 41.59 minutes and 64.43 minutes for upper-lung-lobe-located thoracic tumors and ultracentrally located thoracic tumors, respectively. CONCLUSIONS: To our knowledge, this is the first broad treatment-time analysis for online ART in the literature. Although treatment times are long due to human- and technology-related limitations, benefits offered by MRgRT might be clinically important. In the future, implementation of artificial intelligence segmentation, an increase in dose rate, and faster multileaf collimator and gantry speeds may lead to achieving shorter MRgRT treatments.

Risk of symptomatic radiation necrosis in patients treated with stereotactic radiosurgery for brain metastases.

INTRODUCTIO: Stereotactic radiosurgery (SRS) is a treatment option in the initial management of patients with brain metastases. While its efficacy has been demonstrated in several prior studies, treatment-related complications, particularly symptomatic radiation necrosis (RN), remains as an obstacle for wider implementation of this treatment modality. We thus examined risk factors associated with the development of symptomatic RN in patients treated with SRS for brain metastases. PATIENTS AND METHODS: We performed a retrospective review of our institutional database to identify patients with brain metastases treated with SRS. Diagnosis of symptomatic RN was determined by appearance on serial MRIs, MR spectroscopy, requirement of therapy, and the development of new neurological complaints without evidence of disease progression. RESULTS: We identified 323 brain metastases treated with SRS in 170 patients from 2009 to 2018. Thirteen patients (4%) experienced symptomatic RN after treatment of 23 (7%) lesions. After SRS, the median time to symptomatic RN was 8.3 months. Patients with symptomatic RN had a larger mean target volume (p<0.0001), and thus larger V100% (p<0.0001), V50% (p<0.0001), V12Gy (p<0.0001), and V10Gy (p=0.0002), compared to the rest of the cohort. Single-fraction treatment (p=0.0025) and diabetes (p=0.019) were also significantly associated with symptomatic RN. CONCLUSION: SRS is an effective treatment option for patients with brain metastases; however, a subset of patients may develop symptomatic RN. We found that patients with larger tumor size, larger plan V100%, V50%, V12Gy, or V10Gy, who received single-fraction SRS, or who had diabetes were all at higher risk of symptomatic RN.

Management of symptomatic radiation necrosis after stereotactic radiosurgery and clinical factors for treatment response.

PURPOSE: Approximately 10% of patients who received brain stereotactic radiosurgery (SRS) develop symptomatic radiation necrosis (RN). We sought to determine the effectiveness of treatment options for symptomatic RN, based on patient-reported outcomes. MATERIALS AND METHODS: We conducted a retrospective review of 217 patients with 414 brain metastases treated with SRS from 2009 to 2018 at our institution. Symptomatic RN was determined by appearance on serial magnetic resonance images (MRIs), MR spectroscopy, requirement of therapy, and development of new neurological complaints without evidence of disease progression. Therapeutic interventions for symptomatic RN included corticosteroids, bevacizumab and/or surgical resection. Patient-reported therapeutic outcomes were graded as complete response (CR), partial response (PR), and no response. RESULTS: Twenty-six patients experienced symptomatic RN after treatment of 50 separate lesions. The mean prescription dose was 22 Gy (range, 15 to 30 Gy) in 1 to 5 fractions (median, 1 fraction). Of the 12 patients managed with corticosteroids, 6 patients (50%) reported CR and 4 patients (33%) PR. Of the 6 patients managed with bevacizumab, 3 patients (50%) reported CR and 1 patient (18%) PR. Of the 8 patients treated with surgical resection, all reported CR (100%). Other than surgical resection, age ≥54 years (median, 54 years; range, 35 to 81 years) was associated with CR (odds ratio = 8.40; 95% confidence interval, 1.27-15.39; p = 0.027). CONCLUSION: Corticosteroids and bevacizumab are commonly utilized treatment modalities with excellent response rate. Our results suggest that patient's age is associated with response rate and could help guide treatment decisions for unresectable symptomatic RN.

Long-term toxicity and survival outcomes after stereotactic ablative radiotherapy for patients with centrally located thoracic tumors.

Background Stereotactic ablative radiotherapy (SABR) is effective for thoracic cancer and metastases; however, adverse effects are greater for central tumors. We evaluated factors affecting outcomes and toxicities after SABR for patients with primary lung and oligometastatic tumors. Patients and methods We retrospectively identified consecutive patients with centrally located lung tumors that were treated at our hospital from 2009-2016. The effects of patient, disease, and treatment-related parameters on local control (LC), overall survival (OS), and toxicity-free survival (TFS) were evaluated with multivariate analyses. Results Among 65 consecutive patients identified with 70 centrally located tumors, 20 tumors (28%) were reirradiated. Median (range) total dose for all tumors was 55 (30-60) Gy in 5 (3-10) fractions. Radiographic complete response was obtained in 43 lesions (61%). None of the analyzed factors were correlated with complete response. After a median follow-up of 57 (95% CI, 48-65) months, 10 tumors (14%) relapsed and 37 patients (57%) died; the actuarial 2- and 5-year OS rates were 52% and 28%, respectively. Median OS was significantly lower in patients with grade 3 or higher toxicity vs. lower toxicity (5 vs. 39 months; P < 0.001). Among 17 severe toxicities, 5 were grade 5, and 3 of them were reirradiated to the same field. Grade 3 to 5 TFS was lower with vs. without reirradiation (2-year TFS, 63% vs. 96%; P = 0.02). Conclusions Our study showed that modern SABR is effective for central lung tumors, and toxicities are acceptable. SABR for reirradiated central lung lesions and possibly for lesions abutting the tracheobronchial tree may result in higher risk of serious toxicities.

Output factors of ionization chambers and solid state detectors for mobile intraoperative radiotherapy (IORT) accelerator electron beams.

PURPOSE: The electron energy characteristics of mobile intraoperative radiotherapy (IORT) accelerator LIAC® differ from commonly used linear accelerators, thus some of the frequently used detectors can give less accurate results. The aim of this study is to evaluate the output factors (OFs) of several ionization chambers (IC) and solid state detectors (SS) for electron beam energies generated by LIAC® and compare with the output factor of Monte Carlo model (MC) in order to determine the adequate detectors for LIAC® . METHODS: The OFs were measured for 6, 8, 10, and 12 MeV electron energies with PTW 23343 Markus, PTW 34045 Advanced Markus, PTW 34001 Roos, IBA PPC05, IBA PPC40, IBA NACP-02, PTW 31010 Semiflex, PTW 31021 Semiflex 3D, PTW 31014 Pinpoint, PTW 60017 Diode E, PTW 60018 Diode SRS, SNC Diode EDGE, and PTW 60019 micro Diamond detectors. Ion recombination factors (ksat ) of IC were measured for all applicator sizes and OFs were corrected according to ksat . The measured OFs were compared with Monte Carlo output factors (OFMC ). RESULTS: The measured OFs of IBA PPC05, PTW Advanced Markus, PTW Pinpoint, PTW microDiamond, and PTW Diode E detectors are in good agreement with OFMC . The maximum deviations of IBA PPC05 OFs to OFMC are -1.6%, +1.5%, +1.5%, and +2.0%; for PTW Advanced Markus +1.0%, +1.5%, +2.0%, and +2.0%; for PTW Pinpoint +2.0%, +1.6%, +4.0%, and +2.0%; for PTW microDiamond -1.6%, +2%, +1.1%, and +1.0%; and for PTW Diode E -+1.7%, +1.7%, +1.3%, and +2.5% for 6, 8, 10, and 12 MeV, respectively. PTW Roos, PTW Markus, IBA PPC40, PTW Semiflex, PTW Semiflex 3D, SNC Diode Edge measured OFs with a maximum deviation of +5.6%, +4.5%, +5.6%, +8.1%, +4.8%, and +9.6% with respect to OFMC , while PTW Diode SRS and IBA NACP-02 were the least accurate (with highest deviations -37.1% and -18.0%, respectively). CONCLUSION: The OFs results of solid state detectors PTW microDiamond and PTW Diode E as well as the ICs with small electrode spacing distance such as IBA PPC05, PTW Advanced Markus and PTW Pinpoint are in excellent agreement with OFMC . The measurements of the other detectors evaluated in this study are less accurate, thus they should be used with caution. Particularly, PTW Diode SRS and IBA NACP-02 are not suitable and their use should be avoided in relative dosimetry measurements under high dose per pulsed (DPP) electron beams.