Local radiotherapy for chemotherapy-refractory Kaposi's sarcoma in an HIV-infected patient: A case report and literature review.

Human immunodeficiency virus-associated Kaposi's sarcoma (HIV-KS) is a well-documented vascular tumor with a pathogenesis involving human herpesvirus-8 (HHV-8) infection. While antiretroviral therapy (ART) and chemotherapy are effective for treating most KS cases, some become refractory. In this report, we present a case of a 58-year-old man with refractory HIV-KS treated with ART and chemotherapy. Chemotherapy was eventually discontinued due to an adverse reaction, and the patient presented with painful plantar lesions that impaired ambulation. With the exclusion of visceral metastases, localized radiotherapy was administered, which resulted in significant cosmetic and functional improvements. The patient regained ambulation and lived independently, receiving additional radiotherapy as needed. This case underscores the potential use of radiotherapy for the treatment of ART-resistant KS, particularly when the patient is unresponsive to conventional chemotherapy. It also highlights the need for future research in this area.

[Impact of Respiratory Waveform on Gate Signal Generation on Respiratory Gated Irradiation and Evaluation Method of Respiratory Waveform to Be Used].

PURPOSE: The respiratory gated irradiation using the real-time position management system (RPM) was used to clarify the generation of the gated signal when the respiration waveform changed, and also the evaluation method of the respiration waveform was also examined. METHODS: The respiratory waveform was changed using a moving phantom. Respiratory waveform was analyzed from the data recorded in RPM, and the out-of-phase gated rate was examined. Analysis was made by focusing on the coefficient of variation of the respiratory wavelength in the evaluation of respiratory waveform. RESULTS: Immediately after the change of respiratory wavelength from the short cycle to the long cycle, a gated signal was generated at a phase before the set gated phase, and a maximum advance of 1.259 ± 0.212 s occurred. Immediately after the change of respiratory wavelength from the long cycle to the short cycle, the gated signal was generated at the phase exceeding the set gated phase, and a delay of 0.997 ± 0.180 s occurred at the maximum. As the value of the coefficient of variation increased, the gated rate which was out of setting also increased. CONCLUSION: In respiratory gated irradiation using RPM, it became clear that the gated signal is generated out of the phase set by the respiratory waveform change. Coefficient of variation of the respiratory wavelength is considered to be an indicator for evaluating the respiratory waveform to be used in the respiratory gated irradiation.

[Effects of Low MU in Respiratory Gated IMRT on MLC Position Accuracy and Dose Distribution].

PURPOSE: The purpose of this research is to clarify the effects of low monitor unit (MU) on multileaf collimator (MLC) position accuracy and dose distribution in intensity modulated radiotherapy (IMRT) using respiratory gated. METHOD: In the phantom experiment, irradiation without respiratory gated and respiratory gated with low MU (3, 5, and 7 MU) were performed, and positional accuracy and dose distribution of MLC were analyzed. MLC positional accuracy was calculated from the log-files and the MLC position error, gap size error, MLC leaf speed were calculated and compared with the planned value. Gamma analysis of the dose distribution obtained from the irradiated films and the dose distribution of the treatment plans were carried out. RESULTS: Without respiratory gated and respiratory gated, the frequency of gap size error that did not exceed 0.2 mm were more than 93% under all conditions. MLC position error increased with increasing MLC leaf speed. The determination coefficient of respiratory gated irradiation was lower by about 20% compared with that without respiratory gated, and variation from the approximate straight line occurs. The output difference due to low MU irradiation during respiratory gated was within 1% of the planned value. Although, the pass rate of gamma analysis differed in tumor size, the dose distribution well conformity at 96% or more for both without respiratory gated and respiratory gated. However, in the comparison of the profile in the MLC movement direction, respiratory gated irradiation at 3 MU showed a difference of about 9% at the edge of the irradiated field and about 6% at the point where the dose rapidly changed. CONCLUSION: It was shown that MLC position accuracy due to stop and go of MLC leaf can be secured even with low MU irradiation of about 3 MU. However, attention should be paid to the dose of risk organs adjacent to the tumor margin.

Is scintigraphy necessary to detect migration of 125I seeds after brachytherapy for early prostate cancer?

BACKGROUND: We investigated whether scintigraphy was superior to radiography for detecting migrated seeds after brachytherapy for prostate cancer. METHODS: We studied 57 patients with early prostate cancer who were treated with free (125)I transperineal brachytherapy. Scintigraphy was used to detect seed migration on postoperative day (POD) 1, radiography was used on POD 2, and both tests were used on POD 30. RESULTS: The total number of implanted seeds in this study was 3,753 in 57 patients. Overall, there were 19 seed migrations in 12 patients. On POD 1, there were 4 seed migrations in 4 patients that were detected by scintigraphy. On POD 2, there were 10 seed migrations in 9 patients that were detected by radiography. On POD 30, 17 seed migrations were detected in 10 patients by radiography and 18 seeds migrations were detected by scintigraphy. However, 1 seed migration which was located outside of the detectable range of radiography was detected only by scintigraphy. CONCLUSIONS: Both scintigraphy and radiography have similar abilities to detect migrated seeds 1 month after (125)I brachytherapy for prostate cancer. While both tests have advantages and disadvantages, it is reasonable to only use radiography if scintigraphy is not available.

External Beam Radiotherapy in Advanced Pheochromocytoma and Paraganglioma: An Observation of a Rare Abscopal Effect.

Metastatic pheochromocytoma and paraganglioma are incurable, and effective treatment of systemic symptoms resulting from catecholamine excess and local symptoms from tumor growth are crucial to prolong survival and improve quality of life. We report the first case of metastatic pheochromocytoma wherein external beam radiotherapy (EBRT) demonstrated efficacy in both target and nontarget lesions, demonstrating the "abscopal effect." EBRT reduced tumor volume and catecholamine secretion and improved catecholamine excess-related complications, including glycemic control. EBRT is an effective treatment option for metastatic pheochromocytoma and paraganglioma because of its minimal invasiveness, safety, and potential for the rare abscopal effect.

Prostate-specific antigen doubling time predicts the efficacy of site-directed therapy for oligoprogressive castration-resistant prostate cancer.

Background: In recent years, site-directed therapies (SDTs) targeting progressive lesions in patients with oligometastatic prostate cancer have attracted attention. However, whether they effectively treat oligoprogressive castration-resistant prostate cancer (CRPC) remains unclear. Here, we investigated the efficacy of SDT in patients with oligoprogressive CRPC and identified prognostic factors. Methods: We reviewed 59 patients with oligoprogressive CRPC who underwent SDT targeting prostate or metastatic lesions between April 2014 and March 2022. We evaluated the associations between several pretreatment clinical variables and treatment procedures and a >50% prostate-specific antigen (PSA) response, progression-free survival (PFS), and time to next treatment (TTNT). Results: A PSA response of >50% was observed in 66% of patients. The median PFS and TTNT were 8.3 months and 9.9 months, respectively. Patients with PSA doubling time ≥6 months showed a higher >50% PSA response rate (87% vs. 45%; P < 0.001), longer PFS (median, 15.0 vs. 5.0 months; P < 0.001), and longer TTNT (median, 16.3 vs. 5.9 months; P < 0.001) than patients with PSA doubling time <6 months. In multivariate analyses, a PSA doubling time of ≥6 months independently predicted a >50% PSA response, favorable PFS, and TTNT (P = 0.037, 0.025, and 0.017, respectively). Conclusion: PSA doubling time of ≥6 months may be a key indicator of the favorable efficacy of SDT for oligoprogressive CRPC.

Change in cancer diagnosis during the COVID-19 pandemic: Trends estimated from FDG-PET/CT.

The aim of this study is to clarify changes in the circumstances of cancer diagnoses during the COVID-19 pandemic in Tokyo, Japan, estimated from [18F]-2-fluoro-2-deoxy-D-glucose (FDG) -positron emission tomography/ computed tomography (PET/CT) for cancer patients. Cancer diagnosis in pandemic status (PANS) was evaluated by retrospective review of the findings of FDG-PET/CT examinations performed between 11 March 2020 and 28 December 2021 for initial staging and restaging for malignancy. Evaluation of cancer diagnosis in pre-pandemic status (pPANS) was conducted similarly in FDG-PET/CT examinations performed between 4 January 2018 and 10 March 2020. Of these, patients with malignant lymphoma (ML), lung cancer, esophageal cancer, and colorectal cancer who had a pathologically proven diagnosis or clinical diagnosis following therapy of the disease were selected for analysis. Initial cancer staging was determined by the diagnostic report of FDG-PET/CT. Change in cancer stage and in the number of FDG-PET/CT examinations performed was evaluated between pPANS and PANS, and according to term of the pandemic and vaccination status. The COVID-19 epidemic influenced the number of cancer patients who underwent FDG-PET/CT. There was a marked decrease in the number of cancer patients receiving FDG-PET/CT in Terms 1-3 (March 2020 to February 2021), but it recovered in Terms 4-6 (March 2021 to December 2021). There was no significant difference between PANS and pPANS in terms of the initial stage of cancer, but Stage IV ML and Stage II esophageal cancer were more frequent in PANS. Initial staging of ML, lung cancer, and esophageal cancer revealed more advanced cancer stages in Terms 4-6 compared with Terms 1-3. The number of patients receiving FDG-PET/CT in Tokyo was influenced by the COVID-19 epidemic. Staging based on FDG-PET/CT shifted to more advanced cancer stage during the pandemic compared with pre-pandemic.

The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study.

Purpose: Intensity-modulated radiotherapy (IMRT) is currently used more commonly than 3-dimensional conformal radiation for definitive thoracic radiation. We examined the efficacy profiles of concurrent chemoradiotherapy (CCRT) with IMRT after durvalumab became clinically available. Methods: We reviewed the clinical records of patients with stage III non-small cell lung cancer (NSCLC) treated with CCRT and IMRT at seven centers in Japan and investigated relapse and survival from May 2018 to December 2019. The primary endpoint of this report was progression-free survival (PFS). Results: Among 107 patients enrolled in the study, 87 were sequentially administered durvalumab. From CCRT commencement, patients were followed up for a median period of 29.7 months. The median PFS at the end of the CCRT was 20.7 months. Among the 87 patients, 58 experienced disease relapses, of whom 36 (62.1 %) had distant metastases. Multivariate Cox regression analysis revealed that a favorable response to CCRT, a radiation dose ≥ 62 Gy, and stage IIIA NSCLC were associated with prolonged PFS (all P = 0.04). Multivariate logistic regression by landmark analysis revealed that mortality risk factors were durvalumab treatment duration ≤ 11.7 months, a lower maximum grade of immune-related adverse events, FEV1 < 2805 mL, and radiation dose < 62 Gy (P = 0.01, 0.01, 0.03, and 0.04, respectively). Conclusions: In patients with NSCLC receiving CCRT using IMRT, long PFS was associated with a better response to CCRT, stage IIIA NSCLC, and an increased radiation dose. The duration of durvalumab consolidation also played an essential role in the survival of patients receiving CCRT with IMRT. (250 words).

Chronic eosinophilic pneumonia with subpleural curvilinear shadow.

We report a rare case of chronic eosinophilic pneumonia with subpleural curvilinear shadow. CT scan showed a patchy consolidation in the bilateral upper lungs. In addition, subpleural curvilinear shadow was found in the bilateral upper lungs. A bronchoalveolar lavage obtained from the right middle lobe showed 25 % eosinophils. Although very rare, we should therefore keep in mind that patients, who have patchy consolidation with areas of subpleural curvilinear shadow in the bilateral upper lungs, may have chronic eosinophilic pneumonia.

Proton therapy for patients with esophageal cancer: History, characteristics, clinical outcome and future direction of proton beam therapy.

After the second war, Wilson who participated in development of the atomic bomb in Los Alamos studied peaceful use of atomic energy and proposed a property of proton beam that has potential to treat cancer. According to his proposal, the first patient was treated with proton beam therapy at the University of California Berkley in 1954. The first series of proton beam therapy for patients with esophageal cancer was reported from Japan in 1993. After that many proton facilities in Japan reported the clinical outcome of patients with esophageal cancer. Many dosimetric and clinical studies showed proton beam therapy for esophageal cancer was less toxic than photon beam therapy, however there is a paucity of randomized trials and evidence that proton beam therapy has clearly superior survival compared to photon therapy. Only one randomized trial has been conducted to study less toxicity for proton beam compared with intensity modulated radiotherapy (IMRT), which was stopped early because toxicities of IMRT were higher. A phase III study comparing overall survival between proton beam therapy and IMRT is now activated. A cost reduction for proton therapy is necessary to facilitate patient care and establishment of clinical evidence.

Surgical strategies for treatment of clinical T4 esophageal cancer in Japan.

Definitive chemoradiation (dCRT) is the mainstay treatment for cStage IVa esophageal squamous cell carcinoma (ESCC) with good performance status (PS), according to standard practice guidelines. Salvage surgery may incur operation complications and risk of mortality. According to the esophageal cancer practice guidelines outlined by the Japan Esophageal Society, when a tumor is residual and recurrent, chemotherapy and palliative symptomatic treatment is continued. However, salvage operation has been selected as a therapeutic option for recurrent or residual tumors after dCRT. There is weak evidence for not recommending surgery for cStage IVa ESCC exhibiting residual disease following dCRT. It has been reported that during salvage surgery the only prognostic factor that is thought to be performed is complete resection (R0), but at the same time, salvage esophagectomy increases the incidence of postoperative complications and mortality. The phase II chemoselection study by Yokota T et al. in Japan showed that multidisciplinary treatment initiated by induction therapy, in which docetaxel is added to cisplatin and 5-fluorouracil, resulted in a good prognosis in the short term. In this review, we discuss the surgical strategy and future of unresectable clinical T4 (cT4) ESCC.

Intensity-modulated radiation therapy with concurrent chemotherapy followed by durvalumab for stage III non-small cell lung cancer: A multi-center retrospective study.

BACKGROUND AND PURPOSE: Intensity-modulated radiation therapy (IMRT) is increasingly applied in concurrent chemoradiotherapy (CCRT) for locally-advanced non-small cell lung cancer (NSCLC), with improvement of target coverage and better sparing of normal tissue. IMRT tends to have a larger low-dose irradiation volume than 3D conformal radiotherapy, but the incidence of and risk factors for pneumonitis remain unclear, especially following the approval of durvalumab. MATERIALS AND METHODS: We retrospectively reviewed the records of NSCLC patients treated by CCRT using IMRT at seven Japanese institutions. Primary outcomes were incidence of symptomatic pneumonitis and progression-free survival (PFS). Multivariate logistic regression analysis was used to identify risk factors for ≥grade 2 pneumonitis. RESULTS: Median follow-up from the start of CCRT was 14.3 months (n = 107 patients; median age 70 years, 29% female). Median lung V5 and V20 was 49.2% and 19.5%, respectively. Durvalumab was administered to 87 patients (81%). Pneumonitis developed in 95 (89%) patients of which 53% had grade 1, 28% grade 2, 6.5% grade 3, and 0.9% grade 4. Durvalumab had been discontinued in 16 patients (18.4%) due to pneumonitis. By multivariate analysis, age ≥70 years, male sex, and V5 ≥58.9% were identified as significantly associated with ≥grade 2 pneumonitis (p = 0.0065, 0.036 and 0.0013 respectively). The median PFS from the start of CCRT was not reached (95% CI, 14.2 months to not reached) in patients receiving durvalumab. CONCLUSION: CCRT using IMRT followed by durvalumab was generally effective and tolerable; V5 <60% would be recommended to avoid symptomatic pneumonitis.

Clinical results of proton-beam therapy for locoregionally advanced esophageal cancer.

PURPOSE: To evaluate the efficacy and safety of proton-beam therapy for locoregionally advanced esophageal cancer. PATIENTS AND METHODS: The subjects were 51 patients with esophageal cancer who were treated between 1985 and 2005 using proton beams with or without X-rays. All but one had squamous cell carcinoma. Of the 51 patients, 33 received combinations of X-rays (median 46 Gy) and protons (median 36 GyE) as a boost. The median total dose of combined X-rays and proton radiation for these 33 patients was 80 GyE (range 70-90 GyE). The other 18 patients received proton-beam therapy alone (median 79 GyE, range 62-98 GyE). RESULTS: Treatment interruption due to radiation-induced esophagitis or hematologic toxicity was not required for any patient. The overall 5-year actuarial survival rate for the 51 patients was 21.1% and the median survival time was 20.5 months (95% confidence interval 10.9-30.2). Of the 51 patients, 40 (78%) showed a complete response within 4 months after completing treatment and seven (14%) showed a partial response, giving a response rate of 92% (47/51). The 5-year local control rate for all 51 patients was 38.0% and the median local control time was 25.5 months (95% confidence interval 14.6-36.3). CONCLUSION: The results suggest that proton-beam therapy is an effective treatment for patients with locally advanced esophageal cancer. Further studies are required to determine the optimal total dose, fractionation schedules, and best combination of proton therapy with chemotherapy.

Technical considerations for noncoplanar proton-beam therapy of patients with tumors proximal to the optic nerve.

PURPOSE: To investigate technical feasibilities of noncoplanar proton-beam therapy (PBT) on dose reduction to critical organs. MATERIAL AND METHODS: The degree of mechanical precision, rotational limitations of the gantry and the treatment couch were evaluated, and dose-volume histograms were compared for noncoplanar and coplanar PBT. Following these studies, three patients with tumors proximal to the optic nerve underwent noncoplanar PBT. RESULTS: Noncoplanar PBT offered advantage in dose reduction to the optic nerve when compared to coplanar therapy. This advantage was more significant if the tumor reduced in size during treatment. None experienced radiation injury to the optic nerve during a short follow-up time of 7-12 months. CONCLUSION: Noncoplanar PBT appears to reduce doses to organs at risk.

Risk of radiation pneumonitis in patients with emphysema after stereotactic body radiotherapy for non-small cell lung cancer assessed by quantitative CT.

Quantitative CT assessment of patients with pulmonary emphysema is used to measure pulmonary function. The present study evaluated whether the quantitative CT value can accurately estimate the risk of radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) in patients with and without emphysema. A total of 80 patients with stage I NSCLC receiving SBRT at a dose of 50 or 60 Gy in five fractions at our hospital between November 2003 and October 2015 were included in the analysis. A total of 33 (41%) patients were diagnosed with emphysema on CT examination. Dosimetric parameters, quantitative CT percentage value of low attenuation area (LAA%) in the whole lung, and average whole lung CT density values were used to examine the risk of RP. Among the 80 patients, 26 (33%) and 3 (4%) experienced Grade 1 and Grade 2 RP, respectively, during the median observation period of 18.8 (1.8-106.8) months. The RP rate for patients with a LAA% (<-910 HU) of ≤25% was significantly higher than that of subjects with LAA% (<-910 HU) >25% (P=0.037). The RP rate in subjects with an average HU value of >-790 HU was significantly higher compared with that of patients with ≤-790 HU (P=0.036). Age (hazard ratio [HR]=2.46; P=0.03) and average HU (HR=3.39; P=0.02) were significantly associated with RP, whereas mean lung dose was not identified to be significant in multivariate analysis. The quantitative CT value was associated with RP after SBRT.

Comparisons of dose-volume histograms for proton-beam versus 3-D conformal x-ray therapy in patients with stage I non-small cell lung cancer.

PURPOSE: Dose-volume histograms (DVHs) were reviewed to determine if there is an advantage of the two modalities when treating patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: 24 stage I NSCLC patients who underwent proton-beam therapy (PBT) from June 2003 to May 2007 were included in this study. Based on the same clinical target volumes (CTVs), treatment planning was made to cover CTV within 90% isodose lines. Each patient was evaluated by two sets of DVHs, one for PBT and the other for three-dimensional conformal X-ray therapy (3D-CRT). RESULTS: For all patients, the 95% isodose line covered 86.4% of the CTV for PBT, and 43.2% for 3D-CRT. PBT was associated with significantly lower mean doses to the ipsilateral lung, total lung, heart, esophagus, and spinal cord than 3D-CRT. PBT offered reduced radiation doses to the lung when evaluated in terms of percentage lung volumes receiving > or = 5 Gy (V(5)), > or = 10 Gy (V(10)), and > or = 20 Gy (V(20)) when compared to 3D-CRT. CONCLUSION: PBT is advantageous over 3D-CRT in reducing doses to the lung, heart, esophagus, and spinal cord in treating stage I NSCLC.

Proton-beam therapy for hepatocellular carcinoma associated with portal vein tumor thrombosis.

BACKGROUND AND PURPOSE: The prognosis of patients with advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is extremely poor, as effective treatment options are limited. The authors performed a retrospective review to evaluate the efficacy of proton-beam therapy (PBT) for patients presenting with PVTT in the setting of HCC. PATIENTS AND METHODS: Between February 1991 and September 2005, 35 patients with HCC and tumor thrombi in the main trunk or major branches of the portal vein presented for consideration of PBT. Their tumor sizes ranged from 25 mm to 130 mm (median, 60 mm). A median total dose of 72.6 GyE in 22 fractions was delivered over 31 days to a target volume that encompassed both the primary hepatic lesion and the PVTT. RESULTS: 32 patients were progression-free during a median follow-up period of 21 months (range, 2-88 months) and three patients experienced disease progression. Local progression-free survival rates were 46% at 2 years and 20% at 5 years, and the median local progression-free survival was 21 months. Acute toxicity > or = grade 3 was observed in three patients, and no patient experienced late toxicity > or = grade 3. None of the patients had to discontinue treatment as a result of toxicity. CONCLUSION: PBT improved local control and significantly prolonged survival in HCC patients with PVTT.

Malignant myoepithelioma in the maxillary sinus: case report and review of the literature.

Malignant myoepithelioma of the head and neck usually arises in the salivary glands. We experienced a rare case with malignant myoepithelioma in the maxillary sinus. A 47-year-old woman with malignant myoepithelioma in the maxillary sinus underwent partial maxillectomy. However, local recurrence occurred 28 months after surgery and she was subsequently treated with radiation therapy with proton beams. The recurrent tumor showed complete response and the patient was alive with no evidence of disease 30 months after irradiation. No therapy-related severe toxicities were observed. A rare case with malignant myoepithelioma in the maxillary sinus was successfully treated with radiation therapy.

Thoracic radiotherapy for mediastinal nodal recurrence.

Radiotherapy has been used to treat loco-regional recurrences located at various intra-thoracic sites, but long-term survival of these patients has been rarely observed. We report herein a lung adenocarcinoma patient with locoregional recurrence, who was successfully treated with high-dose radiotherapy. The patient could survive with no evidence of recurrence 5 years after thoracic irradiation. It is probably safe to administrate high-dose radiotherapy for some loco-regional recurrent patients with favorable prognostic factors such as good PS, no body weight loss. Further studies will be required to define a favorable subset of patients most likely to benefit from an aggressive approach.

Phase II study of compensator-based non-coplanar intensity-modulated radiotherapy for Stage I non-small-cell lung cancer.

We conducted a Phase II study to evaluate the usefulness of compensator-based non-coplanar intensity-modulated radiotherapy (ncIMRT) for patients with surgically inaccessible Stage I non-small-cell lung cancer (NSCLC). Patients with pathologically proven or clinically diagnosed surgically inaccessible Stage I NSCLC were enrolled in this study from May 2011 to April 2014. These patients underwent ncIMRT of 75 Gy in 30 fractions regardless of the tumor location. The primary end point was 3-year overall survival, and the secondary end points were local control rate and treatment-related toxicities. A total of 48 patients (50 tumors) were enrolled in this study. Of the 50 tumors, the Stage T1 to T2 ratio was 31 to 19, and the ratio of tumors located in the central to peripheral areas was 11 to 39. During the median follow-up time of 35.9 months, the 3-year actuarial local progression-free and overall survival rates were 82.6% and 87.1%, respectively. No patients experienced toxicities of Grade 3 or greater. Standard-fractionated ncIMRT was effective and safe for patients with surgically inaccessible stage I NSCLC, regardless of the tumor location.