Monte Carlo simulation study of an in vivo four-dimensional tracking system with a diverging collimator for monitoring radiation source (Ir-192) location during brachytherapy: proof of concept and feasibility.

Introduction: The aim of this study was to demonstrate the potential of an in vivo four-dimensional (4D) tracking system to accurately localize the radiation source, Iridium-192 (Ir-192) in high-dose rate brachytherapy. Methods: To achieve time-dependent 3D positioning of the Ir-192 source, we devised a 4D tracking system employing multiple compact detectors. During the system's design phase, we conducted comprehensive optimization and analytical evaluations of the diverging collimator employed for detection purposes. Subsequently, we executed 3D reconstruction and positioning procedures based on the 2D images obtained by six detectors, each equipped with an optimized diverging collimator. All simulations for designing and evaluating the 4D tracking system were performed using the open-source GATE (v9.1) Monte Carlo platform based on the GEANT4 (v10.7) toolkit. In addition, to evaluate the accuracy of the proposed 4D tracking system, we conducted simulations and 3D positioning using a solid phantom and patient data. Finally, the error between the reconstructed position coordinates determined by the tracking system and the original coordinates of the Ir-192 radiation source was analyzed. Results: The parameters for the optimized diverging collimator were a septal thickness of 0.3 mm and a collimator height of 30 mm. A tracking system comprising 6 compact detectors was designed and implemented utilizing this collimator. Analysis of the accuracy of the proposed Ir-192 source tracking system found that the average of the absolute values of the error between the 3D reconstructed and original positions for the simulation with the solid phantom were 0.440 mm for the x coordinate, 0.423 mm for the y coordinate, and 0.764 mm for the z coordinate, and the average Euclidean distance was 1.146 mm. Finally, in a simulation based on data from a patient who underwent brachytherapy, the average Euclidean distance between the original and reconstructed source position was 0.586 mm. Discussion: These results indicated that the newly designed in vivo 4D tracking system for monitoring the Ir-192 source during brachytherapy could determine the 3D position of the radiation source in real time during treatment. We conclude that the proposed positioning system has the potential to make brachytherapy more accurate and reliable.

Five-Fraction High-Conformal Ultrahypofractionated Radiotherapy for Primary Tumors in Metastatic Breast Cancer.

PURPOSE: To report on the local control and toxicity of 5-fraction, high-conformal ultrafractionated radiation therapy (RT) for primary tumors in patients with metastatic breast cancer (MBC) who did not undergo planned surgical intervention. METHODS: We retrospectively reviewed 27 patients with MBC who underwent 5-fraction high-dose ultrafractionated intensity-modulated RT for their primary tumors between 2017 and 2022 at our institution. A median dose of 66.8 Gy (range, 51.8-83.6 Gy) was prescribed to the gross tumor, calculated in 2-Gy equivalents using an α/ß ratio of 3.5, along with a simultaneous integrated boost of 81.5%. The primary endpoint of this study was local control. RESULTS: The median tumor size and volume were 5.1 cm and 112.4 cm3, respectively. Treatment was generally well tolerated, with only 15% of the patients experiencing mild acute skin toxicity, which resolved spontaneously. The best infield response rate was 82%, with the objective response observed at a median time of 10.8 months post-RT (range, 1.4-29.2), until local progression or the last follow-up. At a median follow-up of 18.3 months, the 2-year local control rate was 77%. A higher number of prior lines of systemic therapy was significantly associated with poorer 2-year local control (one-two lines, 94% vs three or more lines, 34%; p = 0.004). Post-RT, 67% of the patients transitioned to the next line of systemic therapy, and the median duration of maintaining the same systemic therapy post-RT was 16.3 months (range, 1.9-40.3). CONCLUSION: In our small dataset, 5-fraction, high-conformal ultrahypofractionated breast RT offered promising 2-year local control with minimal toxicity. Further studies are warranted to investigate the optimal dose and role in this setting.

Long-term Outcomes of Protocol-Based Treatment for Newly Diagnosed Medulloblastoma.

PURPOSE: The Korean Society of Pediatric Neuro-Oncology (KSPNO) conducted treatment strategies for children with medulloblastoma (MB) by using alkylating agents for maintenance chemotherapy or tandem high-dose chemotherapy (HDC) with autologous stem cell rescue (ASCR) according to the risk stratification. The purpose of the study was to assess treatment outcomes and complications based on risk-adapted treatment and HDC. MATERIALS AND METHODS: Fifty-nine patients diagnosed with MB were enrolled in this study. Patients in the standard-risk (SR) group received radiotherapy (RT) after surgery and chemotherapy using the KSPNO M051 regimen. Patients in the high-risk (HR) group received two and four chemotherapy cycles according to the KSPNO S081 protocol before and after reduced RT for age following surgery and two cycles of tandem HDC with ASCR consolidation treatment. RESULTS: In the SR group, 24 patients showed 5-year event-free survival (EFS) and overall survival (OS) estimates of 86.7% (95% confidence interval [CI], 73.6 to 100) and 95.8% (95% CI, 88.2 to 100), respectively. In the HR group, more infectious complications and mortality occurred during the second HDC than during the first. In the HR group, the 5-year EFS and OS estimates were 65.5% (95% CI, 51.4 to 83.4) and 72.3% (95% CI, 58.4 to 89.6), respectively. CONCLUSION: High intensity of alkylating agents for SR resulted in similar outcomes but with a high incidence of hematologic toxicity. Tandem HDC with ASCR for HR induced favorable EFS and OS estimates compared to those reported previously. However, infectious complications and treatment-related mortalities suggest that a reduced chemotherapy dose is necessary, especially for the second HDC.

Assessment of Bone Marrow Involvement in Extranodal NK/T-Cell Lymphoma: Positron Emission Tomography versus Bone Marrow Biopsy, and the Significance of Minimal Involvement by EBV+ Cells (KROG 18-09).

PURPOSE: This study aims to investigate the diagnostic significance of positron emission tomography/computed tomography (PET/CT) in assessing bone marrow (BM) involvement through a comparison of PET/CT findings with BM biopsy in extranodal natural killer/T-cell lymphoma. MATERIALS AND METHODS: The medical records of 193 patients were retrospectively reviewed. Patients were categorized as having early-stage (PET-ES) or advanced-stage (PET-AS) disease based on PET/CT results. The BM involvement was classified into three groups according to BM biopsy: gross BM involvement, minimal BM involvement (defined as the presence of a limited number of Epstein-Barr virus-positive cells in BM), and no involvement. Calculations of the accuracy of PET/CT in detecting BM involvement and analysis of the clinical outcomes (progression-free survival [PFS] and overall survival [OS]) according to the BM biopsy status were performed. RESULTS: PET/CT exhibited a sensitivity of 64.7% and a specificity of 96.0% in detecting gross BM involvement. For detecting any (both gross and minimal) BM involvement, the sensitivity was 30.4%, while the specificity was 99.0%. Only one patient (0.7%) demonstrated gross BM involvement among the PET-ES group. Survival outcomes of the PET-ES group with minimal BM involvement (3-year PFS, 55.6%; OS, 77.0%) were closer to those of the PET-ES group with no BM involvement (3-year PFS, 62.2%; OS, 80.6%) than to those of the PET-AS group (3-year PFS, 20.1%; OS, 29.9%). CONCLUSION: PET/CT exhibits high specificity, but moderate and low sensitivity in detecting gross and minimal BM involvement, respectively. The clinical significance of minimal BM involvement for patients in the PET-ES group may be limited.

Large institutional experience of early outcomes and dosimetric findings with postoperative stereotactic partial breast irradiation in breast cancer.

PURPOSE: To analyze the dosimetric and toxicity outcomes of patients treated with postoperative stereotactic partial breast irradiation (S-PBI). METHODS: We identified 799 women who underwent S-PBI at our institution between January 2016 and December 2022. The most commonly used dose-fraction and technique were 30 Gy in 5 fractions (91.7 %) and a robotic stereotactic radiation system with real-time tracking (83.7 %). The primary endpoints were dosimetric parameters and radiation-related toxicities. For comparison, a control group undergoing ultra-hypofractionated whole breast irradiation (UF-WBI, n = 468) at the same institution was selected. RESULTS: A total of 815 breasts from 799 patients, with a median planning target volume (PTV) volume of 89.6 cm3, were treated with S-PBI. Treatment plans showed that the mean and maximum doses received by the PTV were 96.2 % and 104.8 % of the prescription dose, respectively. The volume of the ipsilateral breast that received 50 % of the prescription dose was 32.3 ± 8.9 %. The mean doses for the ipsilateral lung and heart were 2.5 ± 0.9 Gy and 0.65 ± 0.39 Gy, respectively. Acute toxicity occurred in 175 patients (21.5 %), predominantly of grade 1. Overall rate of late toxicity was 4 % with a median follow-up of 31.6 months. Compared to the UF-WBI group, the S-PBI group had comparably low acute toxicity (21.5 % vs. 25.2 %, p = 0.12) but significantly lower dosimetric parameters for all organs-at-risks (all p < 0.05). CONCLUSION: In this large cohort, S-PBI demonstrated favorable dosimetric and toxicity profiles. Considering the reduced radiation exposure to surrounding tissues, external beam PBI with advanced techniques should at least be considered over traditional WBI-based approaches for PBI candidates.

CyberKnife based fractionated stereotactic radiotherapy as an upfront treatment for cerebral arteriovenous malformation.

BACKGROUND: To explore the therapeutic outcomes of CyberKnife based fractionated stereotactic radiotherapy (CKFRT) for patients with cerebral arteriovenous malformations (AVM). METHODS: Between January 2008 and October 2020, 45 patients underwent CKFRT for cerebral AVMs as a first treatment. The delineation of AVM targets included AVM nidus. The mean target volume was 4.07 cm3, and 9 lesions (20%) were larger than 10.0 cm3. The mean marginal dose was 24 Gy (range, 20-35 Gy). CKFRT was delivered in median 3 fractions (range, 2 âˆ¼ 5 fractions). AVM obliteration following CKFRT was confirmed by magnetic resonance imaging or angiography. RESULTS: During a median follow-up of 47 (5-148) months, complete obliteration and partial obliteration of AVM after CKFRT were obtained in 23 (51%) and 13 (29%) patients, respectively. Median time to complete obliteration was 39 (15-63) months. The cumulative probability of complete obliteration rate at 3 years was 47%. Complete obliteration rate of AVM was associated with Radiosurgery-based AVM score, which was consisted of AVM volume, patients age, and AVM location. One (2%) patient had hemorrhage during the follow-up period. CONCLUSIONS: CKFRT is an effective primary treatment for patients with cerebral AVMs with a low hemorrhage risk.

CyberKnife-based stereotactic radiosurgery or fractionated stereotactic radiotherapy in older patients with brain metastases from non-small cell lung cancer.

PURPOSE: We analyzed clinical results of CyberKnife (CK)-based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) in older patients (age ≥65 years) affected by brain metastases (BM) from non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Forty-three older patients with 92 BM were treated with CK-based SRS/FSRT at our institution between 2009 and 2019. The end-point was overall survival (OS). Univariate and multivariate analyses were performed to identify the prognostic factors influencing OS. The in-field local control (IFLC) within the SRS/FSRT field was also assessed. RESULTS: During a median follow-up period of 18 months, the median OS was 32 months. NSCLC-specific graded prognostic assessment (GPA) (p = 0.027) was an independent significant factor affecting OS in the multivariate analysis. The median IFLC period was 31 months, and the total BM volume (p = 0.025) appeared to be a significant feature of IFLC. No adverse events >grade 2 were reported after SRS/FSRT. CONCLUSION: CK-based SRS/FSRT is a safe and efficient option for older patients with BM arising from NSCLC, showing good OS without severe side effects. GPA, which was consisted in age, performance status, extra-cerebral metastasis, and number of BM, seemed to be predictive factors for OS.

Dummy run quality assurance study in the Korean Radiation Oncology Group 19 - 09 multi-institutional prospective cohort study of breast cancer.

BACKGROUND: The Korean Radiation Oncology Group (KROG) 19 - 09 prospective cohort study aims to determine the effect of regional nodal irradiation on regional recurrence rates in ypN0 breast cancer patients. Dosimetric variations between radiotherapy (RT) plans of participating institutions may affect the clinical outcome of the study. We performed this study to assess inter-institutional dosimetric variations by dummy run. METHODS: Twelve participating institutions created RT plans for four clinical scenarios using computed tomography images of two dummy cases. Based on a reference structure set, we analyzed dose-volume histograms after collecting the RT plans. RESULTS: We found variations in dose distribution between institutions, especially in the regional nodal areas. Whole breast and regional nodal irradiation (WBI + RNI) plans had lower inter-institutional agreement and similarity for 95% isodose lines than WBI plans. Fleiss's kappa values, which were used to measure inter-institutional agreement for the 95% isodose lines, were 0.830 and 0.767 for the large and medium breast WBI plans, respectively, and 0.731 and 0.679 for the large and medium breast WBI + RNI plans, respectively. There were outliers in minimum dose delivered to 95% of the structure (D95%) of axillary level 1 among WBI plans and in D95% of the interpectoral region and axillary level 4 among WBI + RNI plans. CONCLUSION: We found inter-institutional and inter-case variations in radiation dose delivered to target volumes and organs at risk. As KROG 19 - 09 is a prospective cohort study, we accepted the dosimetric variation among the different institutions. Actual patient RT plan data should be collected to achieve reliable KROG 19 - 09 study results.

Trends in the incidence of thyroid cancer in Incheon Province, South Korea, from 2004 to 2013: A representative sample study from Incheon cancer registry.

AIM: This study aimed to assess the trends in the incidence of thyroid cancer in Incheon Province, South Korea, from 2004 to 2013 and to identify its association with thyroid cancer screening. METHODS: We evaluated randomly sampled data of 10% of thyroid cancer patients collected between 2004 and 2013 from the Incheon Cancer Registry, Incheon, South Korea. The expected annual incidence rates of thyroid cancer from 2004 to 2013 were calculated, and the trends in annual incidence change were assessed using a Poisson regression model. In addition, the annual proportion change in the thyroid cancer population according to the detection method and tumor size was also calculated by evaluating the linear-by-linear association. RESULTS: The average expected prevalence of thyroid cancer was 30 per 100,000 individuals from 2004 to 2013. The expected annual incidence of thyroid cancer per 100,000 individuals increased from 7 in 2004 to 49 in 2013, with an annual 1.25-fold difference (p < 0.001). Screening helped improve the detection of thyroid cancer annually, with the proportion increasing by screening detection (p < 0.001). Majority (54%) of the tumors were small (< 10 mm) and their detection rate increased from 2004 to 2013 (p < 0.001). CONCLUSIONS: The incidence of thyroid cancer has increased from 2004 to 2013 in Incheon Province, South Korea, with the increase being most significant for small tumors. These findings indicate that the increased incidence is primarily due to the widespread use of screening and not an actual increase in clinically significant thyroid cancer.

Metastasis-Directed Radiotherapy for Oligoprogressive or Oligopersistent Metastatic Colorectal Cancer.

INTRODUCTION: Some patients with cancer may present with progressive or persistent disease at a limited number of sites following a period of treatment response. We evaluated the safety and effectiveness of metastasis-directed radiotherapy (MRT) for oligoprogressive or oligopersistent disease in patients receiving systemic treatment for metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with mCRC who received 5-fluorouracil, leucovorin, and oxaliplatin; 5-fluorouracil, leucovorin, and irinotecan; and/or capecitabine chemotherapy between 2011 and 2020 at a single institution were identified. Then, those who underwent MRT for five or fewer lesion sites while receiving systemic treatment for other metastases were categorized. The primary endpoint was time to change to systemic therapy. Secondary endpoints included MRT-related toxicity, overall survival, and local control. RESULTS: Among 4157 patients included, 91 (2%) received MRT to limited lesion sites (55 oligoprogressive and 36 oligopersistent) during systemic treatment following a period of treatment response. The median time to change to next-line systemic therapy was 5 months in the overall cohort (measured from the current chemotherapy session) and 9.5 (range, 6.0-40.6) months in the MRT group (measured from the MRT session). No severe toxicity or systemic treatment interruption was observed following MRT. The 1-year local control and overall survival rates were 69% and 99%, respectively. CONCLUSION: In patients with oligoprogressive or oligopersistent mCRC, MRT may be performed safely in conjunction with systemic treatment to maximize the benefit of systemic therapy and to prolong the time to change to systemic therapy. Further prospective studies should confirm these findings.

Survey of radiation field and dose in human papillomavirus-positive oropharyngeal cancer: is de-escalation actually applied in clinical practice?

PURPOSE: Studies on de-escalation in radiation therapy (RT) for human papillomavirus-related (HPV(+)) oropharyngeal cancer (OPC) are currently ongoing. This study investigated the current practice regarding the radiation dose and field in the treatment of HPV(+) OPC. MATERIALS AND METHODS: The Korean Society for Head and Neck Oncology conducted a questionnaire on the primary treatment policy. Among them, for HPV(+) OPC scenarios, radiation oncologists were questioned regarding the field and dose of RT. RESULTS: Forty-two radiation oncologists responded to the survey. In definitive concurrent chemoradiotherapy (CCRT) treatment for stage T2N1M0 OPC, most respondents prescribed a dose of >60 Gy to the primary tonsil and involved ipsilateral lymph nodes. However, eight of the respondents prescribed a relatively low dose of ≤54 Gy. For stage T2N1M0 OPC, postoperative adjuvant RT was prescribed by eight and nine respondents with a lower dose of ≤50 Gy for the ipsilateral tonsil and involved neck, respectively. In definitive CCRT in complete remission after induction chemotherapy for initial stage T2N3M0 OPC, de-escalation of the tonsil and involved neck were performed by eight and seven respondents, respectively. Regarding whether de-escalation is applied in radiotherapy for HPV(+) OPC, 27 (64.3%) did not do it at present, and 15 (35.7%) were doing or considering it. CONCLUSION: The field and dose of prescribed treatment varied between institutions in Korea. Among them, dose de-escalation of RT in HPV(+) OPC was observed in approximately 20% of the respondents. Consensus guidelines will be set in the near future after the completion of ongoing prospective trials.

Implications of Radiotherapy Utilization in Korea from 2010 to 2019.

BACKGROUND: This study was to assess the rate of radiotherapy (RT) utilization according to the modality in South Korea to identify the implications of contemporary RT patterns. METHODS: We collected information from claims and reimbursement records of the National Health Insurance Service from 2010 to 2019. We classified the location of each institution as capital (Seoul, Incheon, and Gyeonggi-do) and non-capital areas. RESULTS: The rate of RT utilization in total cancer patients nationwide was 24.5% in 2010, which consistently has increased to 36.1% in 2019 (annual increase estimate [AIE], 4.5%). There was an abrupt increase in patients receiving intensity-modulated RT (IMRT), with an AIE of 33.5%, and a steady decline in patients receiving three-dimensional conformal RT (3DCRT), with an AIE of -7.1%. The commonest RT modality was IMRT (44.5%), followed by 3DCRT and stereotactic RT (SRT) (37.2% and 13.5%) in 2019. An increasing trend of advanced RT (such as IMRT and SRT) utilization was observed regardless of the region, although the AIE in the capital areas was slightly higher than that in non-capital areas. CONCLUSION: The utilization of overall RT application and especially of advanced modalities remarkably increased from 2010 to 2019. We also found gaps in their AIEs between capital and non-capital areas. We should ensure that advanced RT is accessible to all cancer patients across South Korea.

Recent Treatment Patterns of Oropharyngeal Cancer in Korea Based on the Expert Questionnaire Survey of the Korean Society for Head and Neck Oncology (KSHNO).

PURPOSE: The incidence of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) has increased, and staging and optimal therapeutic approaches are challenging. A questionnaire survey was conducted to investigate the controversial treatment policy of stage T2 OPC according to the N category and determine the opinions of multidisciplinary experts in Korea. MATERIALS AND METHODS: Five OPC scenarios were developed by the Subcommittee on Oropharyngeal Treatment Guidelines of the Korean Society for Head and Neck Oncology and distributed to experts of multidisciplinary treatment hospitals. RESULTS: Sixty-five experts from 45 institutions responded. For the HPV-positive T2N0M0 scenario, 67.7% of respondents selected surgery followed by definitive concurrent chemoradiotherapy (CCRT) or radiotherapy alone. For the T2N1M0 HPV-positive scenario, there was a notable difference in the selection of primary treatment by expert specialty; 53.9% of respondents selected surgery and 39.8% selected definitive CCRT as the primary treatment. For the T2N3M0 advanced HPV-positive scenario, 50.0% of respondents selected CCRT and 33.3% considered induction chemotherapy (IC) as the primary treatment. CCRT and IC were significantly more frequently selected for the HPV-related OPC cases (p=0.010). The interdepartmental variability showed that the head and neck surgeons and medical oncologists favored surgery, whereas the radiation oncologists preferably selected definitive CCRT (p < 0.001). CONCLUSION: In this study, surgery was preferred for lymph node-negative OPC, and as lymph node metastasis progressed, CCRT tended to be preferred, and IC was administered. Clinical practice patterns by stage and HPV status showed differences according to expert specialty. Multidisciplinary consensus guidelines will be essential in the future.

Optimal treatment strategies for small cell carcinoma of the uterine cervix: A retrospective multi-center study (KROG 19-03).

OBJECTIVE: This multi-institutional study aimed to identify the optimal treatment strategy for small cell carcinoma of the cervix. STUDY DESIGN: We retrospectively collected the medical records of 166 patients diagnosed with small cell carcinoma of the uterine cervix from January 2000 to December 2015 from 13 institutions of the Korean Radiation Oncology Group. After excluding 18 (10.8 %) patients who initially had distant metastasis, the treatment outcomes of 148 patients were analyzed. RESULTS: After a median 46.4 (1.4-231.9) months of follow-up, the 5-year progression-free survival (PFS) and overall survival (OS) rates of all patients were 45.9 % and 63.5 %, respectively. Distant metastasis was the dominant pattern of failure occurring in 67 patients (45.3 %). We stratified the patients according to the primary local treatment: primary surgery (n = 119), primary radiotherapy (RT) (n = 26), and no local treatment group (n = 3). Although the primary RT group had advanced disease (FIGO stage ≧ IIB) more frequently than the primary surgery group (80.8 % vs. 47.9 %), the PFS and OS did not differ between the groups in multivariate analysis. CONCLUSION: Definitive RT is a reasonable local treatment option for small cell cervical cancer, particularly for advanced cases. Given the high rates of distant relapse, an effective systemic therapy protocol is warranted for small cell cervical cancer patients.

Impact of radiation dose on complications among women with breast cancer who underwent breast reconstruction and post-mastectomy radiotherapy: A multi-institutional validation study.

PURPOSE: Emerging data suggest that higher radiation doses in post-mastectomy radiotherapy may be associated with an increased risk of reconstruction complications. This study aimed to validate previous findings regarding the impact of radiation dose on complications among women with breast cancer using a multi-center dataset. METHODS: Fifteen institutions participated, and women with breast cancer who received radiotherapy after either autologous or prosthetic breast reconstruction were included. The primary endpoint was major post-radiation therapy complications requiring re-operation for explantation, flap failure, or bleeding control. RESULTS: In total, 314 patients were included. Radiotherapy was performed using both conventional fractionation and hypofractionation in various schedules. The range of the radiation therapy dose in Equivalent Dose in 2 Gy fractions (EQD2; α/ß = 3.5) varied from 43.4 to 71.0 Gy (median dose: 48.6 Gy). Boost radiation therapy was administered to 49 patients. Major post-radiation therapy complications were observed in 24 (7.6%) patients. In multivariate analysis, an increasing EQD2 per Gy (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.26-1.98; p < 0.001), current smoking status (OR: 25.48, 95% CI: 1.56-415.65; p = 0.023), and prosthetic breast reconstruction (OR: 9.28, 95% CI: 1.84-46.70; p = 0.007) were independently associated with an increased risk of major complications. CONCLUSION: A dose-response relationship between radiation dose and the risk of complications was validated in this multi-center dataset. In this context, we hypothesize that the use of hypofractionated radiotherapy (40 Gy in 15 fractions) may improve breast reconstruction outcomes. Our multi-center prospective observational study (NCT03523078) is underway to further validate this hypothesis.

Intensity-Modulated Radiotherapy-Based Reirradiation for Head and Neck Cancer: A Multi-institutional Study by Korean Radiation Oncology Group (KROG 1707).

PURPOSE: The benefits of reirradiation for head and neck cancer (HNC) have not been determined. This study evaluated the efficacy of reirradiation using intensity-modulated radiotherapy (IMRT) for recurrent or second primary HNC (RSPHNC) and identified subgroups for whom reirradiation for RSPHNC is beneficial. MATERIALS AND METHODS: A total of 118 patients from seven Korean institutions with RSPHNC who underwent IMRT-based reirradiation between 2006 and 2015 were evaluated through retrospective review of medical records. We assessed overall survival (OS) and local control (LC) within the radiotherapy (RT) field following IMRT-based reirradiation. Additionally, the OS curve according to the recursive partitioning analysis (RPA) suggested by the Multi-Institution Reirradiation (MIRI) Collaborative was determined. RESULTS: At a median follow-up period of 18.5 months, OS at 2 years was 43.1%. In multivariate analysis, primary subsite, recurrent tumor size, interval between RT courses, and salvage surgery were associated with OS. With regard to the MIRI RPA model, the class I subgroup had a significantly higher OS than class II or III subgroups. LC at 2 years was 53.5%. Multivariate analyses revealed that both intervals between RT courses and salvage surgery were prognostic factors affecting LC. Grade 3 or more toxicity and grade 5 toxicity rates were 8.5% and 0.8%, respectively. CONCLUSION: IMRT-based reirradiation was an effective therapeutic option for patients with RSPHNC, especially those with resectable tumors and a long interval between RT courses. Further, our patients' population validated the MIRI RPA classification by showing the difference of OS according to MIRI RPA class.

Reirradiation with intensity-modulated radiation therapy for recurrent or secondary head and neck cancer: Meta-analysis and systematic review.

BACKGROUND: To summarize outcomes of reirradiation with intensity-modulated radiotherapy (IMRT) for recurrent or secondary head and neck cancer (HNC). METHODS: Primary endpoints were 2-year local control (LC) and overall survival (OS). Studies involving only recurrent nasopharyngeal patients with cancer were excluded. RESULTS: A total of 17 studies involving 1635 patients were included. Fourteen (82%) of those were retrospective, and 15 (88%) were from single institution. Reirradiation with IMRT produced pooled 2-year LC and OS rates of 52% (95% confidence interval [CI], 46%-57%) and 46% (95% CI, 41%-50%), respectively. In subgroup analyses, the rate of salvage surgery (<42% vs ≥42%) influenced the pooled 2-year LC rate (45.9% vs 58.5%, P = .011). The pooled rates of late grade ≥ 3 and grade 5 toxicities were 26% (95% CI, 20%-32%) and 3.1% (95% CI, 2%-5%), respectively. CONCLUSIONS: Reirradiation with IMRT was an effective modality compared to historical outcomes in the pre-IMRT era.

Reirradiation using stereotactic body radiotherapy in the management of recurrent or second primary head and neck cancer: A meta-analysis and systematic review.

OBJECTIVES: We conducted a meta-analysis and systematic review of stereotactic body radiotherapy (SBRT)-based reirradiation efficacy in patients with recurrent or second primary head and neck cancer (RSHNC). METHODS: We systematically reviewed PubMed/MEDLINE, Embase, and Cochrane Library. The primary endpoint was 2-year overall survival (OS); secondary endpoints were grade >3 complications and response rate. RESULTS: We included 10 studies involving 575 patients (only 12% of whom underwent salvage surgery post-recurrence) with RSHNC who underwent SBRT; median SBRT reirradiation doses ranged from 24 to 44 Gy (median, 30 Gy) delivered with 3-6 fractions (median, 5 fractions). Median target volume of SBRT reirradiation was measured from 19 to 103 cm3. The pooled event rate of 2-year OS following SBRT reirradiation for RSHNC was 30.0% (95% confidence interval [CI] 24.5-36.1). The pooled rates of late grade ≥3 and grade 5 toxicity were 9.6% (95% CI 5.0-17.6) and 4.6% (95% CI 2.4-8.6), respectively. Grade 5 toxicity was not observed in five studies (range: 0-10.7%). The pooled rates of clinical response and complete response were 61.7% (95% CI 51.1-71.3) and 31.3% (95% CI 23.3-40.5), respectively, and the 2-year local control rate was 47.3% (95% CI 3.1-62.1). CONCLUSIONS: SBRT with median 30 Gy in 5 fractions is a feasible therapy showing good responses for patients with RSHNC not suitable for salvage surgery. However, to improve OS, SBRT reirradiation strategy should be investigated in terms of dose escalation for sustained control and combined systemic therapy.

Clinical Outcomes of Immune Checkpoint Blocker Therapy for Malignant Melanoma in Korean Patients: Potential Clinical Implications for a Combination Strategy Involving Radiotherapy.

PURPOSE: We investigated the clinical efficacy of immune checkpoint blocker (ICB) therapy for metastatic or advanced melanoma in Korean patients. As well, we assessed whether the effects of ICBs can be enhanced by combination therapy with palliative radiotherapy (RT). MATERIALS AND METHODS: We retrospectively reviewed the records of 127 patients with metastatic melanoma who received ICB with or without palliative RT between 2014 and 2018. The melanoma subtypes were classified as follows: chronic sun-damaged (CSD), acral, mucosal, and uveal. The primary endpoint was the objective response rate (ORR). RESULTS: The overall ORR was 15%, with 11 complete and eight partial responses. ORRs for CSD, acral/mucosal, and uveal melanomas were 50%, 16.5%, and 0%, respectively (p=0.009). In addition to the subtype, stage at treatment, total tumor burden at treatment, and ICB type were significantly associated with ORR (all p < 0.05). Palliative RT was administered in 44% of patients during the treatment, and it did not affect ORR. Clinical responders to ICB therapy exhibited significantly higher 1-year progression-free and overall survival rates than nonresponders. CONCLUSION: ORR for ICB monotherapy in Korean patients with melanoma is relatively modest compared with that in Western patients because the non-CSD subtypes are predominant in the Korean population. Our findings regarding combination therapy with ICB provided a rationale for the initiation of our phase II study (NCT04017897).

Comparisons between radiofrequency ablation and stereotactic body radiotherapy for liver malignancies: Meta-analyses and a systematic review.

INTRODUCTION: Radiofrequency ablation (RFA) is a standard ablative modality for small liver malignancies. Stereotactic body radiotherapy (SBRT) has emerged although yet suffers a lack of high-level evidence. We performed meta-analyses and a systematic review to integrate the literature and help in clinical decision-making. METHODS: Systemic searches were performed of the PubMed, Medline, and EMBASE databases to identify controlled studies comparing RFA and SBRT. RESULTS: Eleven studies involving 2238 patients were included. Among them, eight studies were for treating early hepatocellular carcinomas (HCCs) and three for liver metastases. Including HCCs and liver metastases studies, the pooled two-year local control (LC) rate was higher in the SBRT arm (83.8%, 95% confidence interval [CI]: 77.6-88.4) than that in the RFA arm (71.8%, 95% CI: 61.5-80.2) (p = 0.024). Among studies on liver metastases, the pooled two-year LC rate was higher in the SBRT arm (83.6% vs. 60.0%, p < 0.001). No significant difference was found between arms in HCC studies (SBRT vs. RFA: 84.5 vs. 79.5% p = 0.431). Pooled analysis of overall survival (OS) in HCC studies showed an odds ratio of 1.43 (95% CI: 1.05-1.95, p = 0.023), favoring RFA. Among the two liver metastases studies with comparative survival data, no significant difference was observed. CONCLUSION: LC was equivalent between RFA and SBRT for HCC and better for SBRT for the treatment of liver metastases. RFA was associated with better OS for HCC, but discrepancy between LC and OS requires further investigation, as they are local modalities having comparable efficacy.