The role of postoperative radiotherapy in hepatocellular carcinoma

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Efficacy of radiotherapy for gastric bleeding associated with advanced gastric cancer

Background: Gastric bleeding negatively impacts the quality of life of patients with unresectable advanced gastric cancer and is frequently lethal. We investigated the efficacy of RT for palliation of gastric bleeding from gastric cancer and identified an optimal radiotherapy (RT) strategy. Methods: The study analyzed 57 patients submitted to palliative RT for gastric bleeding associated with gastric cancer between January 2009 and February 2019. Changes in hemoglobin (Hb) levels were analyzed based on measurements taken before and immediately, 1 month, and 2 months after RT. Re-bleeding after RT was identified as either Hb level dropping to < 7.0 g/dL or the administration of a blood transfusion after RT. Results: The median biologically effective dose (α/β = 10) was 37.5 Gy (range 23.6-58.5). The most common regimen was 25 Gy in five fractions. The mean Hb levels before, immediately after, 1 month, and 2 months after RT (6.6, 9.7, 10.3, and 9.7 g/dL, respectively) were significantly higher than that before RT (all p < 0.001). No significant differences in re-bleeding rates were observed according to total dose, fractional dose, and fraction number. Gastric tumor response evaluated by computed tomography within 2 months after RT showed partial responses were more frequent in patients achieving bleeding control (25.0% vs. 10.8%, p = 0.023) and overall survival was significantly improved for bleeding control within 3 months after RT (median, 15.4 vs. 10.0 weeks, p = 0.048). Conclusions: RT was an effective modality for gastric bleeding control in gastric cancer, which can be achieved with a short course scheme with five fractions.ope

Skull Base Metastasis from Hepatocellular Carcinoma: Clinical Presentation and Efficacy of Radiotherapy

Purpose: Skull base metastasis (SBM) from hepatocellular carcinoma (HCC) presents detrimental survival outcomes with cranial nerve symptoms; however, they have received little attention. This study aimed to investigate the clinical presentation and efficacy of radiation therapy (RT) in patients with SBM from HCC. Patients and methods: We identified patients with SBM from HCC in Yonsei Cancer Center from 2005 to 2019. Image evaluations and SBM-related symptoms were reviewed. Overall survival was calculated using the Kaplan-Meier method and compared through the Log rank test. The oligometastasis group included patients with less than five foci of tumors, while the extensive metastasis group presented five or more sites. Results: The incidence of SBM from HCC was 1.5% (58/3793 patients), commonly found in the middle cranial fossa. SBM associated symptoms presented in 51 patients, and the most common were head and neck area pain, and orbital symptoms, The palliation rate after RT was 65% (24/39 patients) for overall symptoms and 83.3% (20/24 patients) for cranial nerve symptoms. In whole cohort, overall survival was analyzed, and the median overall survival of patients with oligometastasis was better than extensive metastasis (23.7 months vs 1.8 months, p < 0.001). In subgroup who received RT (39 patients), the median overall survival was 23.7 and 2.7 months for patients with oligo and extensive metastasis, respectively (p < 0.001). Conclusion: This study confirmed clinical features of SBM from HCC. Overall survival was generally poor, but patients presenting oligometastasis seemed to have possibility of relative long-term survival. Although radiation was effective in SBM-induced symptom relief, dose-response relationship in local control rate and overall survival needs further studies with larger number of patients.ope

Skeletal Muscle Depletion Predicts the Prognosis of Patients With Hepatocellular Carcinoma Treated With Radiotherapy

Background: Sarcopenia is gaining attention as a poor prognostic factor for various types of malignancies. This study evaluated the prevalence and prognostic significance of sarcopenia and its association with survival in hepatocellular carcinoma (HCC) patients who underwent radiotherapy (RT) to the primary site. Materials and Methods: Between January 2009 and November 2016, 156 patients with HCC that underwent RT to the liver were retrospectively studied. Sarcopenia was defined as an L3 skeletal muscle index of <49 cm2/m2 for men and <41 cm2/m2 for women as proposed by Korean-specific cut-off value. Sarcopenia was identified pre- and post-RT (within 3 months from the end of RT). Results: Pre-RT sarcopenia occurred in 99 (63.5%) patients and was significantly associated with higher levels of protein induced by vitamin K absence or antagonist-II (PIVKA-II), lower percentage of overweight/obesity (body-mass index), higher percentage of previous systemic chemotherapy, and lower total RT dose. At a median follow-up of 9.3 months, median overall survival (OS) was significantly lower in patients with pre-RT sarcopenia than in those without (7.1 vs. 15.3 months, p < 0.001). In multivariate analysis [reporting hazard ratio (HR): 95% confidence interval (CI)], albumin-bilirubin score (2.35: 1.33-4.17; p = 0.003), total dose (0.44: 0.27-0.71; p = 0.001), and pre-RT sarcopenia (2.38: 1.53-3.70; p < 0.001) were independent OS prognostic factors. Among patients without pre-RT sarcopenia, 20 newly developed sarcopenia after RT and showed significantly lower OS compared to those without sarcopenia after RT (n = 35) (median 14.1 vs. 17.5 months, p = 0.018). Multivariate logistic regression analysis [reporting odds ratio (OR)] demonstrated older age (310.190; p = 0.007), Child-Pugh classification B or C (15.239; p = 0.047), higher alpha-fetoprotein (128.486; p = 0.008), higher PIVKA-II (118.536; p = 0.027), and larger planning target volume (51.310; p = 0.026) as significant factors for newly developed post-RT sarcopenia. Conclusion: Newly developed sarcopenia after RT, as well as pre-RT sarcopenia, were associated with poor survival for HCC patients who underwent RT to the liver. This result suggests the possibility that early intervention such as nutritional support and exercise therapies before and during RT could prevent muscle wasting and may be effective in improving the prognosis of HCC patients.ope

Machine learning‑based radiomics models for prediction of locoregional recurrence in patients with breast cancer

Locoregional recurrence (LRR) is the predominant pattern of relapse after definitive breast cancer treatment. The present study aimed to develop machine learning (ML)‑based radiomics models to predict LRR in patients with breast cancer by using preoperative magnetic resonance imaging (MRI) data. Data from patients with localized breast cancer that underwent preoperative MRI between January 2013 and December 2017 were collected. Propensity score matching (PSM) was performed to adjust for clinical factors between patients with and without LRR. Radiomics features were obtained from T2‑weighted with and without fat‑suppressed MRI and contrast‑enhanced T1‑weighted with fat‑suppressed MRI. In the present study five ML models were designed, three base models (support vector machine, random forest, and logistic regression) and two ensemble models (voting model and stacking model) composed of the three base models, and the performance of each base model was compared with the stacking model. After PSM, 28 patients with LRR and 86 patients without LRR were included. Of these 114 patients, 80 patients were randomly selected to train the models, and the remaining 34 patients were used to evaluate the performance of the trained models. In total, 5,064 features were obtained from each patient, and 47‑51 features were selected by applying variance threshold and least absolute shrinkage and selection operator. The stacking model demonstrated superior performance in area under the receiver operating characteristic curve (AUC), with an AUC of 0.78 compared to a range of 0.61 to 0.70 for the other models. An external validation study to investigate the efficacy of the stacking model of the present study was initiated and is still ongoing (Korean Radiation Oncology Group 2206).ope

Vertebral compression fracture after stereotactic ablative radiotherapy in patients with oligometastatic bone lesions from hepatocellular carcinoma

Background and purpose: Stereotactic ablative radiotherapy (SABR) is popularly used to treat bone metastasis. Despite its efficacy, adverse events, including vertebral compression fracture (VCF), are frequently observed. Here, we investigated VCF risk after SABR for oligometastatic vertebral bone metastasis from hepatocellular carcinoma. Materials and methods: A total of 84 patients with 144 metastatic bone lesions treated at three institutions between 2009 and 2019 were retrospectively reviewed. The primary endpoint was VCF development, either new or progression of a pre-existing VCF. VCFs were assessed using the spinal instability neoplastic score (SINS). Results: Among 144 spinal segments, 26 (18%) had pre-existing VCF and 90 (63%) had soft tissue extension. The median biologically effective dose (BED) was 76.8 Gy. VCF developed in 14 (12%) of 118 VCF-naïve patients and progressed in 20 of the 26 with pre-existing VCF. The median time to VCF development was 6 months (range, 1-12 months). The cumulative incidence of VCF at 12 months with SINS class I, II and III was 0%, 26% and 83%, respectively (p < 0.001). Significant factors for VCF development were pre-existing VCF, soft tissue extension, high BED, and SINS class in univariate analysis, and pre-existing VCF in multivariate analysis. Of the six components of SINS, pain, type of bone lesion, spine alignment, vertebral body collapse, and posterolateral involvement were identified as predictors of VCF development. Conclusion: SABR for oligometastatic vertebral bone lesions from HCC resulted in a substantial rate of new VCF development and pre-existing VCF progression. Pre-existing VCF was significant risk factor for VCF development, which require special attention in patient care. Patients with SINS class III should be considered surgical treatment rather than upfront SABR.ope

Intracranial failure after hippocampal-avoidance prophylactic cranial irradiation in limited-stage small-cell lung cancer patients

We evaluated intracranial failure after hippocampus-avoidance-prophylactic cranial irradiation (HA-PCI) for limited-stage small-cell lung cancer (SCLC). Data of 106 patients who received PCI with 25 Gy were retrospectively reviewed. The patients were divided into two groups based on whether they underwent HA-PCI: the HA-PCI group (n = 48) and the conventional PCI (C-PCI) group (n = 58). Twenty-one patients experienced intracranial failure: 11 and 10 patients in the C-PCI and HA-PCI groups, respectively. Using the log-rank test, the intracranial failure rate was not significantly different between the groups (p = 0.215). No clinical factor was significantly associated with intracranial failure in multivariate Cox regression analysis, but HA-PCI tended to be associated with increased incidence of intracranial failure (HR 2.87, 95% CI 0.86-9.58, p = 0.087). Among patients who received HA-PCI, two developed peri-hippocampal recurrence. A higher thoracic radiotherapy dose (≥ 60 Gy) was significantly associated with DFS (HR 0.52, p = 0.048) and OS (HR 0.35, p = 0.003). However, HA-PCI was associated with neither DFS nor OS. Although HA-PCI may be associated with an increased risk of intracranial failure, HA-PCI did not impair disease control or survival. Future prospective randomized trials are needed to reach a definite conclusion.ope

Clinical features and treatment outcomes of resected large cell neuroendocrine carcinoma of the lung

Purpose: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a high-grade lung neuroendocrine tumor with a poor prognosis, similar to small cell lung cancer (SCLC). However, it remains unclear whether to treat LCNEC as non-small-cell lung cancer (NSCLC) or as SCLC. We reviewed our experiences to suggest appropriate treatment strategy for resected pulmonary LCNEC. Materials and methods: Forty-four patients were treated for pathologically diagnosed pulmonary LCNEC during 2005‒2018. We considered curative surgery first in early-stage or some locally advanced tumors, unless medically inoperable. Adjuvant treatments were decided considering patient's clinical and pathological features. After excluding two stage I tumors with radiotherapy alone and three stage III tumors with upfront chemotherapy, we analyzed 39 patients with stage I‒III pulmonary LCNEC, who underwent curative resection first. Results: Adjuvant chemotherapy (NSCLC-based 91%, SCLC-based 9%) was performed in 62%, and adjuvant radiotherapy was done in three patients for pN2 or positive margin. None received prophylactic cranial irradiation (PCI). With a median follow-up of 30 months, the 2- and 5-year overall survival (OS) rates were 68% and 51%, and the 2- and 5-year recurrence-free survival (RFS) rates were 49% and 43%, respectively. Aged ≥67 years and SCLC-mixed pathology were significant poor prognostic factors for OS or RFS (p < 0.05). Among 17 recurrences, regional failures were most common (n = 6), and there were five brain metastases. Conclusions: Surgery and adjuvant treatment (without PCI) could achieve favorable outcomes in pulmonary LCNEC, which was more similar to NSCLC, although some factors worsened the prognosis. The importance of intensified adjuvant therapies with multidisciplinary approach remains high.ope

Treatment outcomes and radiotherapy deintensification strategies in human papillomavirus-associated tonsil cancer

Background: Human papillomavirus (HPV)-positive tonsil cancer has a better prognosis than HPV-negative tonsil cancer. Deintensification strategies to reduce or avoid radiotherapy (RT) for patients with HPV-associated tonsil cancer have been suggested. This study investigated the treatment outcomes of patients with HPV-associated tonsil cancer and suggested RT deintensification strategies. Methods: A cohort of 374 patients with HPV-associated tonsil cancer treated with primary surgery or RT between 2008 and 2020 was retrospectively evaluated. Survival and locoregional control rates after primary surgery or RT were analyzed, and propensity score matching was performed to adjust for clinical factors. Pearson's chi-square or Fisher's exact test was used to compare categorical variables, and Student's t-test was used to compare continuous variables. The Kaplan-Meier method and log-rank test were used to assess overall survival, progression-free survival, and locoregional failure (LRF). Results: No significant differences in survival or LRF were observed between the primary surgery and RT groups. Subgroup analysis was conducted for patients who underwent primary surgery. Advanced pathological N stage, negative contralateral nodes at diagnosis, abutting or positive surgical margins, and no adjuvant RT were independent risk factors for LRF. Advanced pathological T stage was an independent risk factor for LRF in patients who underwent primary surgery without subsequent adjuvant RT. None of the patients with pathological complete remission (CR) after induction chemotherapy died or experienced LRF. Conclusions: Our study revealed that the outcomes of primary surgery and primary RT in HPV-positive tonsil cancer were similar after adjusting for clinical factors. Primary RT might be considered instead of surgery in patients with advanced pathological T stage. In the case of pathological CR after induction chemotherapy, deintensification for adjuvant RT should be considered.ope

Medical student education through flipped learning and virtual rotations in radiation oncology during the COVID-19 pandemic: a cross sectional research

Background: The COVID-19 pandemic has stripped many medical students worldwide of their right to quality education. In response, we developed hybrid courses involving aspects of both online and in-person teaching for radiation oncology medical student clerkship. Methods: We entitled students to customize their own rotation schedule using Google Forms and developed a flipped learning online class, which consisted of at least one video clip on basic knowledge of radiation oncology per day (yonsei-radonc.com). Students were instructed to watch online videos before the next day's discussion session. Required components of the medical education program (e.g., target drawing, site visits to treatment facilities) were also prepared and conducted in accordance with the appropriate level of social distancing measures. Finally, we conducted questionnaire surveys after the completion of the week-long course and clerkship. Results: From March to June 2020, 110 fourth-year medical students undertook a clinical module in our 1-week radiation oncology program course. Each day, students completed the flipped learning prior to meeting with the educator and then participated in the online discussion session and conference. All activities were well performed as scheduled. Students' motivation was high, as was their overall satisfaction with the course. The students were satisfied with the online contents, flipped learning strategy, and instructors. Conclusions: We successfully integrated open and virtual educational platforms to improve access to and satisfaction with student clerkship. In the future "new normal," minimized face-to-face learning interactions, such as flipped learning, should be actively utilized for medical and other students' education.ope