Recent developments in the field of radiotherapy for the management of lung cancer.

Lung cancer has a poor prognosis, and further improvements in outcomes are needed. Radiotherapy plays an important role in the treatment of unresectable lung cancer, and there have been recent developments in the field of radiotherapy for the management of lung cancer. However, to date, there have been few reviews on the improvement in treatment outcomes associated with high precision radiotherapy for lung cancer. Thus, this review aimed to summarize the recent developments in radiotherapy techniques and indicate the future directions in the use of radiotherapy for lung cancer. Stereotactic body radiotherapy (SBRT) for unresectable stage I lung cancer has been reported to improve local control rates without severe adverse events, such as radiation pneumonitis. For locally advanced lung cancer, a combination of chemoradiotherapy and adjuvant immune checkpoint inhibitors dramatically improves treatment outcomes, and intensity-modulated radiotherapy (IMRT) enables safer radiation therapy with less frequent pneumonitis. Particle beam therapy, such as carbon-ion radiotherapy and proton beam therapy, has been administered as advanced medical care for patients with lung cancer. Since 2024, it has been covered under insurance for early stage lung cancer with tumors ≤ 5 cm in size in Japan. In addition to chemotherapy, local ablative radiotherapy improves treatment outcomes in patients with oligometastatic stage IV lung cancer. A particular problem with radiotherapy for lung cancer is that the target location changes with respiratory motion, and various physical methods have been used to control respiratory motion. Recently, coronavirus disease has had a major impact on lung cancer treatment, and cancer treatment during situations, such as the coronavirus pandemic, must be performed carefully. To improve treatment outcomes for lung cancer, it is necessary to fully utilize evolving radiotherapy modalities, and the role of radiotherapy in lung cancer treatment is expected to increase.

Recurrence Pattern, Treatment Modalities, and Prognostic Factors After Definitive Chemoradiotherapy for Recurrent Esophageal Cancer.

BACKGROUND: Recurrent esophageal cancer (EC) has a poor prognosis. However, the recurrence patterns and therapeutic outcomes after definitive chemoradiotherapy (CRT) are not fully understood. We analyzed survival and prognostic factors associated with post-definitive CRT recurrent EC. METHODS: We retrospectively reviewed 71 consecutive patients with post-definitive CRT EC recurrence between 2008 and 2021 at our institution. Recurrence was locoregional, distant, and combined in 42 (59%), 18 (25%), and 11 (16%) patients, respectively. The median time from definitive CRT to recurrence was 8.3 months. Treatment modalities included local therapy, systemic therapy, and palliative care. Overall survival (OS) after recurrence was analyzed using the Kaplan-Meier and Cox proportional hazards models. RESULTS: The median follow-up time from recurrence was 7.1 months, and the median survival time (MST) was 12.5 months. In the univariate analysis, longer time to recurrence, earlier stage at initial treatment, surgical tolerance at initial diagnosis, treatment modalities, and oligo-recurrence were associated with a better prognosis. The MST of the local therapy, systemic therapy, and palliative care groups were not reached, 11.8 months and 4.1 months, respectively (P < 0.001). In the multivariate analysis, treatment modalities and oligo-recurrence emerged as independent prognostic factors (P < 0.001 and P = 0.009). CONCLUSIONS: Aggressive local therapy should be considered to improve the prognosis for patients with oligo-recurrence and/or indication of local therapy to treat recurrent EC.

The association between initiation weekday of radiotherapy and local control in stage 1 glottic carcinoma: a retrospective analysis.

Radiotherapy is one of the definitive treatments for head and neck squamous cell carcinoma, especially early-stage glottic squamous cell carcinoma. Although there are several studies on the initiation weekday of cancer treatment, there are very few studies in the radiotherapy field. Thus, the present study investigated whether the initiation weekday of radiotherapy affects the local control rate for stage 1 glottic squamous cell carcinoma. A total of 105 patients with stage 1 glottic squamous cell carcinoma underwent definitive radiotherapy alone between 2007 and 2021. The group in which radiotherapy was started between Monday and Wednesday was compared with the group in which radiotherapy was started on Thursday or Friday. Sixty-seven patients started radiotherapy between Monday and Wednesday and 38 on Thursday or Friday. The 5-year local control rate was 98% (95% confidence interval: 94-100%) in the Monday-Wednesday group and 83% (95% confidence interval: 71-96%) in the Thursday-Friday group, with a significant difference (P = 0.005). On multivariate analysis including age, overall administration time (days), fractionation, irradiation field size and initiation weekday of radiotherapy, no factors other than initiation weekday affecting local control were identified. Radiotherapy toxicity did not differ between the two groups. For stage 1 glottic squamous cell carcinoma, starting radiotherapy on Thursday or Friday is associated with a lower local control rate; therefore, radiotherapy should be started by Wednesday.

The efficacy of radiation therapy using the Quad Shot regimen in cutaneous metastasis from parotid gland cancer: A case report.

Cutaneous metastasis from malignant tumors can cause symptoms such as exudates, bleeding, and pain, which remarkably reduce patient's quality of life. Herein, we report a case in which radiation therapy using the Quad Shot regimen was effective in the treatment of cutaneous metastasis from parotid gland cancer.

Successful Preoperative QUAD SHOT for Bulky Parotid Carcinoma: Potential Preoperative Ultra-Hypofractionated Radiotherapy for Conversion Surgery.

QUAD SHOT is an ultra-hypofractionated radiotherapy (RT) technique that prescribes 14.0-14.8 Gy over 2 days. Although this technique has already gained some status as an effective palliative treatment for inoperable head and neck cancer (HNC), its application in other situations has not been given much consideration. Herein, we report a case of a 62-year-old woman who received preoperative QUAD SHOT therapy for poorly differentiated parotid carcinoma. In this case, after two courses of QUAD SHOT plus a standard chemotherapy regimen with pembrolizumab, the patient's inoperable, bulky tumor shrank dramatically and became operable. Best of all, while adequate therapeutic effects were achieved, the patient's time commitment and physical exertion were limited. RT during this period consisted of only eight fractions over 4 days. According to previous reports, the response rate for QUAD SHOT is sufficiently high, and the rate of serious adverse events is quite low. This case asks the question of whether the indications for QUAD SHOT irradiation can be expanded as one of the preoperative interventions undertaken by HNC surgeons to achieve conversion surgery.

Clinical Outcomes of Radiotherapy for Stage 1 Glottic Carcinoma: Comparing Accelerated Hyperfractionation and Once-daily Fractionation.

BACKGROUND/AIM: Accelerated hyperfractionation (AHF) is used in head and neck cancer to improve the local control (LC) rate, but reports of outcomes for early-stage GC are limited. The outcomes of radiotherapy (RT) for stage 1 glottic carcinoma (GC) were retrospectively analyzed, comparing AHF and once-daily fractionation (ODF) using 2.0-2.4 Gy. PATIENTS AND METHODS: A total of 102 patients with stage 1 GC underwent RT alone between 2007 and 2021, with 43 in the AHF group and 59 in the ODF group. A p-value less than 0.05 was considered to indicate a significant difference. RESULTS: The 5-year LC rate was 98% in the AHF group and 91% in the ODF group (p=0.19). During RT, significantly more patients in the AHF group required opioids due to mucositis than in the ODF group (74% vs. 25%, p<0.001), and the rate of aspiration pneumonia tended to be higher in the AHF group than in the ODF group (7% vs. 0%, p=0.072). CONCLUSION: There was no difference in the LC rate between AHF and ODF for stage 1 GC. Moreover, the AHF group required opioids at a higher rate and tended to have a higher risk of developing aspiration pneumonia.

Abscopal Effect after Stereotactic Body Radiotherapy with Nivolumab for Lung Metastasis of Head and Neck Cancer: A Case Report.

Introduction: The abscopal effect (AE) is a phenomenon, in which radiotherapy exerts an antitumour effect on distant lesions outside the primary irradiated area. Although immune checkpoint inhibitors have been widely studied for their potential to enhance the AE and improve patient outcomes, findings in cases of head and neck cancers remain limited. Case Presentation: We report the case of a 72-year-old man who experienced lung oligoprogression during nivolumab treatment for metastatic hypopharyngeal cancer. Stereotactic body radiotherapy (SBRT) was administered to one of the lung lesions, after which both irradiated and nonirradiated lesions regressed. Upon an 18-month follow-up period after SBRT, the patient showed no disease progression or toxicity, and continued receiving nivolumab therapy. Conclusion: The intent behind presenting this case report was to contribute to the accumulation of evidence regarding the AE in cases of head and neck cancer.

Ectopic adrenocortical adenoma in the renal hilum mimicking a renal cell carcinoma.

Ectopic adrenocortical tissue can arise along the path of embryonic migration, such as the celiac axis, broad ligament, adnexa of the testis, and spermatic cord. Occasionally, ectopic adrenocortical tissues undergo marked hyperplasia and develop into ectopic adrenocortical adenomas. This report describes the case of a 60-year-old man who was incidentally found to have a lipid-containing mass with early enhancement and delayed washout in the right renal hilum. A renal cell carcinoma was suspected, and robot-assisted partial nephrectomy was performed, but the final diagnosis was an ectopic adrenocortical adenoma. We should include ectopic adrenocortical adenoma in the differential diagnosis when we find a lipid-containing tumor adjacent to the kidney.

A Case of Ruptured Decidualized Ovarian Endometrioma: Usefulness of Serial MRI for Determining Adequate Management.

Decidualization can originate in ovarian endometrioma by elevated serum progesterone levels during pregnancy, which mimics malignancy on ultrasonography. Moreover, decidualized ovarian endometrioma may rupture and cause acute abdominal pain during pregnancy. Magnetic resonance imaging (MRI) is reportedly useful in differentiating decidualized ovarian endometriomas from malignancies. However, to our knowledge, serial MRI of decidualized ovarian endometrioma before and after rupture has not been reported. Herein, we report the case of a 39-year-old woman with a ruptured decidualized ovarian endometrioma in which serial MRI was useful for adequate management. She had a history of right ovarian endometrioma. Transvaginal ultrasonography at 20 weeks of gestation showed the known right ovarian endometrioma with mural nodules that were not evident before pregnancy. MRI for further evaluation showed ovarian endometrioma with mural nodules with signals similar to those of the placenta. Based on the MRI findings, we diagnosed a decidualized ovarian endometrioma. At 27 weeks of gestation, she complained of sudden abdominal pain, for which MRI was performed. MRI showed disappearance of the ovarian endometrioma and bloody ascites, based on which we diagnosed a ruptured ovarian endometrioma. The abdominal pain subsided immediately, and a conservative observational treatment approach was taken. At 37 weeks of gestation, right ovarian cystectomy was performed simultaneously with an elective cesarean section, which revealed a ruptured decidualized ovarian endometrioma. Our findings demonstrate that the accurate diagnosis of a ruptured decidualized ovarian endometrioma on serial MRI can contribute to its management.

Radiation Myelopathy Caused by Palliative Radiotherapy and Intrathecal Methotrexate.

Radiation myelopathy is a rare, late-stage adverse event that develops following irradiation at or above 50 Gy. Here, we report a case of irreversible paraplegia caused by palliative radiation (20 Gy in 5 fractions) to the spinal cord combined with intrathecal methotrexate (IT-MTX). A 69-year-old man presented with back pain, prompting a diagnosis of acute myeloid leukemia. At the first visit, he complained of muscle weakness and hypoesthesia in both legs; spinal magnetic resonance imaging (MRI) revealed an epidural mass compressing the spinal cord at the fifth to seventh level of the thoracic vertebrae. This was considered to be an extramedullary lesion of leukemia, and he received remission induction therapy including IT-MTX; palliative radiation (20 Gy in 5 fractions) of the epidural mass was initiated the following day. Then, during the course of consolidation therapy, a second IT-MTX was performed after 1 month and a third after 3 months. While the consolidation therapy was complete, yielding remission, he developed sudden paraplegia, as well as bladder and bowel dysfunction (BBD), 10 months later. Spinal MRI showed extensive intramedullary high signal intensity on T2-weighted image, including the irradiation field. It was thought myelopathy was due to irradiation of the spinal cord combined with IT-MTX. He immediately received steroid pulse therapy; however, the paraplegia and BBD did not improve. It is extremely rare for irreversible radiation myelopathy to occur with IT-MTX and palliative radiation to the spinal cord. We believe that even with low-dose palliative radiation, caution is required for combined use with IT-MTX.

Dosimetric Evaluation of the Uterus in Patients Receiving Total Body Irradiation with Ovarian Shielding.

Infertility is a well-known late complication in patients receiving hematopoietic stem cell transplantation (HSCT). We previously reported that total body irradiation (TBI) with ovarian shielding reduces the radiation dose to the ovaries to 2.4 Gy - one-fifth of the dose compared to conventional TBI - and preserves fertility without increasing the risk of relapse. Exposure to the uterus and ovaries can reportedly affect pregnancy and childbirth. However, the dose constraint of the uterus that causes infertility remains unknown. Herein, we report the pregnancy and birth outcomes of 2 patients who gave birth following TBI with ovarian shielding and evaluated the dose to the uterus using a dose-volume histogram. Case 1 involved a 30-year-old woman with acute myeloid leukemia who underwent HSCT at 21 years of age with a uterus mean dose (D mean) of 7.0 Gy. She had a natural pregnancy and elective cesarean section at 38 weeks of gestation due to hypertensive disorders of pregnancy. She gave birth to a normal-birthweight infant. Case 2 involved a 32-year-old woman with T-cell acute lymphoblastic leukemia who underwent HSCT at 30 years of age with a uterus D mean of 7.6 Gy. Her baby was delivered at full term with normal birthweight. These results indicate that a uterus D mean between 7.0 and 7.6 Gy does not have a significant impact on pregnancy and delivery with the ovarian function being preserved for patients who received TBI with ovarian shielding after puberty.

Nintedanib-Induced Delayed Mucosal Healing after Adjuvant Radiation in a Case of Oropharyngeal Carcinoma.

Since the launch of imatinib in 2001, tyrosine kinase inhibitors are being used in chemotherapy for a wide range of malignant tumors. Drugs that inactivate multiple molecular mechanisms are called multikinase inhibitors (MKIs). Nintedanib is a type of MKI that inhibits downstream cascades in three systems: vascular endothelial growth factor receptor, fibroblast growth factor receptor, and platelet-derived growth factor receptor inhibitions. It was initially developed as an anticancer drug for non-small-cell lung carcinoma; however, it was also found to inhibit the proliferation of fibroblasts associated with chronic inflammation in the lungs. Therefore, it is being more widely used to treat idiopathic pulmonary fibrosis, a benign disease, than as an antineoplastic agent. Several studies have reported adverse events associated with the concurrent use of MKIs with surgery or radiotherapy. Specifically, there has been a report cautioning against delayed wound healing associated with the use of nintedanib in patients undergoing surgery. However, there is no specific mention of its concurrent use during irradiation. We describe a case of a 72-year-old man with severely delayed recovery from radiation mucositis when nintedanib was being administered for benign disease.

Palliative Radiotherapy Provided Good Pain Relief for Painful Adrenal Metastasis.

Adrenal metastases often occur in patients with metastasized lung cancer, but symptoms rarely develop. A 45-year-old man presented with right abdominal pain requiring strong opioids due to large right adrenal metastasis of lung adenocarcinoma. The tumor was 7.3 × 5.6 × 8.4 cm in size. He was treated with palliative radiotherapy (RT) up to 39 Gy in 13 fractions for this lesion without severe adverse effects. After RT, he had good pain relief, and opioids were no longer needed. Palliative RT for a large adrenal tumor can provide a good analgesic effect without relevant toxicity.

Cullin-4B E3 ubiquitin ligase mediates Apaf-1 ubiquitination to regulate caspase-9 activity.

Apoptotic protease-activating factor 1 (Apaf-1) is a component of apoptosome, which regulates caspase-9 activity. In addition to apoptosis, Apaf-1 plays critical roles in the intra-S-phase checkpoint; therefore, impaired expression of Apaf-1 has been demonstrated in chemotherapy-resistant malignant melanoma and nuclear translocation of Apaf-1 has represented a favorable prognosis of patients with non-small cell lung cancer. In contrast, increased levels of Apaf-1 protein are observed in the brain in Huntington's disease. The regulation of Apaf-1 protein is not yet fully understood. In this study, we show that etoposide triggers the interaction of Apaf-1 with Cullin-4B, resulting in enhanced Apaf-1 ubiquitination. Ubiquitinated Apaf-1, which was degraded in healthy cells, binds p62 and forms aggregates in the cytosol. This complex of ubiquitinated Apaf-1 and p62 induces caspase-9 activation following MG132 treatment of HEK293T cells that stably express bcl-xl. These results show that ubiquitinated Apaf-1 may activate caspase-9 under conditions of proteasome impairment.

Penetration of high-intensity Er:YAG laser light emitted by IR hollow optical fibers with sealing caps in water.

The penetration depth in water was measured for Er:YAG laser light in a high density relevant to clinical applications. Various types of focusing elements were used to guide the light efficiently. We found that the transmission distance depended strongly on the beam shape in the water. When we used a plano-convex type of focusing cap, the penetration depth was larger than that when a dome- or ball-type cap were used.