A case of massive hemoptysis caused by lung cancer saved by V-V ECMO and hemostasis achieved by radiotherapy.

Massive hemoptysis is one of the fatal complications of lung cancer. There is no established standard treatment method for it, and it often causes sudden suffocation, and some cases may be difficult to save. A 63-year-old man was admitted to the hospital with dyspnea, and developed massive hemoptysis from lung cancer shortly after admission. The tumor had obstructed the right main bronchus and had invaded the right pulmonary artery. Surgery and interventional radiology were judged impossible. The patient was successfully saved by the introduction of Veno-Venous Extra Corporeal Membrane Oxygenation (V-V ECMO), and hemostasis was obtained by radiotherapy. Two months after completion of radiotherapy, he was weaned off the ventilator and discharged on his own. He died of increased peritoneal dissemination and other complications 1 year and 1 month later, but no recurrence of hemoptysis was noted until his death. We experienced a case of massive hemoptysis in which V-V ECMO and radiation therapy succeeded in saving life and stopping bleeding. The use of V-V ECMO by emergency care teams and multimodality therapy, including radiotherapy, were effective for massive hemoptysis from lung cancer.

Multimodal treatment with chemoradiotherapy, regional hyperthermia and interstitial brachytherapy for a huge locally advanced cervical cancer: A case report.

A female patient in her 50 s was found to have a 10-cm tumor resulting from locally advanced cervical cancer (LACC). Three-year relapse-free survival was achieved following a multimodal treatment strategy integrating chemoradiotherapy (CRT), regional hyperthermia (RHT), and interstitial brachytherapy (ISBT). Given the large size of the tumor, enhancement of the geometrical dose distribution was anticipated using ISBT. However, delivery of a sufficient dose to the high-risk clinical target volume was predicted to be challenging. Thus, RHT was incorporated to potentially augment the overall treatment effect. This unique combination of CRT, RHT and ISBT may be promising for management of large LACC and warrants further investigation.

Risk Factors for Radiation Necrosis and Local Recurrence after Proton Beam Therapy for Skull Base Chordoma or Chondrosarcoma.

[Proposal] Here, we retrospectively evaluate risk factors for radiation necrosis and local recurrence after PBT for skull base chordoma or chondrosarcoma. [Patients and Methods] We analyzed 101 patients who received PBT for skull base chordomas and chondrosarcomas from January 1989 to February 2021. Multivariable logistic regression models were applied for local recurrence, temporal lobe radiation necrosis rates, and temporal lobe radiation necrosis. [Results] In multivariate analysis, chordoma and large tumor size were independent significant factors for local recurrence. The 1-, 2-, 3-, 4- and 5-year local recurrence rates were 3.9%, 16.9%, 20.3%, 28.5% and 44.0% for chordoma and 0%, 0%, 0%, 0% and 7.1% for chondrosarcoma, respectively. The local recurrence rates of small tumors (<30 mm) were 4.3%, 14.7%, 17.7%, 17.7% and 25.9%, and those for large tumors were 3.6%, 15.1%, 19.2%, 32.7% and 59.6%, respectively. In multivariate analysis, BED Gy10 and total dose were risk factors for radiation necrosis. [Conclusions] For skull base chordoma and chondrosarcoma, the risk factors of local recurrence were chordoma and large tumor size, and those of radiation necrosis were BED Gy10 and total dose, respectively. DVH analysis is needed to investigate the risk factors for brain necrosis in more detail.

Retrospective Analysis of the Areas Responsible for Light Flash and Odor During Proton Beam Therapy and Photon Therapy.

Background Abnormal sensations were frequently experienced by patients who received irradiation of the brain or head and neck region. We have previously suggested correlations with irradiation of the nasal cavity and retina. Purpose We performed a retrospective dose-volume histogram analysis focused on the brain and head and neck tumor to examine the relationship between these abnormal sensations and the details of irradiation. Methods Multivariate logistic regression models were applied for the presence or absence of light flash and odor. Gender, age, radiotherapy method (proton beam therapy vs. photon radiotherapy), dose of retina, optic nerve, chiasmatic gland, pituitary, nasal cavity, oral cavity, frontal lobe, parietal lobe, occipital lobe, temporal lobe, amygdala, and hippocampus were set as candidates of explanatory variables. Results Light flash and odor during radiotherapy have been suggested to be associated with younger age and retina and nasal cavity irradiation. Multivariate analyses including dose-volume histograms indicated that light flash was related to age, chiasmatic gland irradiation, and pituitary dose, and odor was related to age and nasal cavity irradiation. Conclusion Our results indicate that light flash during radiotherapy is caused by irradiation of the visual pathway and that odor is caused by irradiation of the nasal cavity or olfactory bulb.

Analysis of person-hours required for proton beam therapy for pediatric tumors.

Proton beam therapy (PBT) is effective for pediatric tumors, but patients may require sedation and other preparations, which extend the treatment time. Pediatric patients were classified into sedation and non-sedation cases. Adult patients were classified into three groups based on irradiation from two directions without or with respiratory synchronization and patch irradiation. Treatment person-hours were calculated as follows: (time from entering to leaving the treatment room) × (number of required personnel). A detailed analysis showed that the person-hours required for the treatment of pediatric patients are about 1.4-3.5 times greater than those required for adult patients. With the inclusion of additional time for the preparation of pediatric patients, PBT for pediatric cases is two to four times more labor-intensive than for typical adult cases.

Long-term Outcomes After Moderate Hypofractionated Proton Therapy for Centrally Located Non-small Cell Lung Cancer.

BACKGROUND/AIM: To investigate the outcomes of patients with centrally located non-small-cell lung cancer (NSCLC) treated with proton beam therapy (PBT) using moderate hypofractionation. PATIENTS AND METHODS: Between 2006 and 2019, 34 patients with centrally located T1-T4N0M0 NSCLC who received moderate hypofractionated PBT were retrospectively reviewed. RESULTS: The median follow-up was 50.8 months (range=5.8-100.4 months). The 3-year overall survival, progression-free survival (PFS), and local control rates were 70.4%, 55.5% and 80.5%, respectively. Grade 2 or 3 lung adverse events (AEs) after PBT were observed in five (14.7%) patients; however, grade 3 radiation pneumonitis was observed in one (2.9%) patient. Notably, no grade 4 or higher AEs were observed. Regarding the correlation between the lung dose and proximal bronchial tree maximum dose and grade 2 or higher lung AEs, a weak correlation was observed between the mean lung dose and AEs (p=0.035). Although the clinical target volume (CTV) was a risk factor for poor PFS, no significant correlation was found between the CTV and lung AEs after PBT. CONCLUSION: Moderate hypofractionated PBT may be a useful radiotherapy method for centrally located cT1-T4N0M0 NSCLC.

Clinical Impact of Proton Beam Therapy for Postoperative Lymph Node Oligorecurrence of Esophageal Cancer.

BACKGROUND/AIM: Radiotherapy is a salvage therapy type for postoperative recurrence of esophageal cancer. Compared to conventional photon-based radiotherapy, proton beam therapy can reduce the irradiated dose to the surrounding organs, facilitating the management of patients who are unfit for radiotherapy. In this study, the outcomes and toxicity of proton beam therapy for postoperative lymph node oligorecurrence of esophageal cancer were investigated. PATIENTS AND METHODS: We retrospectively evaluated the clinical outcomes and toxicity of 13 sites in 11 patients treated with proton beam therapy for postoperative lymph node oligorecurrence of esophageal cancer. In total, eight men and three women with a median age of 68 years (range=46-83 years) were included. RESULTS: The median follow-up period was 20.2 months. During the follow-up period, four patients died of esophageal cancer. Eight of the 11 patients developed recurrence; of these, seven patients had recurrence outside the irradiated field, and one had recurrence inside and outside the irradiated field. The 2-year overall survival, progression-free survival, and local control rates were 48.0%, 27.3%, and 84.6%, respectively. The median survival time was 22.4 months. There were no severe acute or late adverse events. CONCLUSION: Proton beam therapy could be a safe and effective treatment method for postoperative lymph node oligorecurrence of esophageal cancer. It may be beneficial even in cases where conventional photon-based radiotherapy is difficult to administer in combination with increased doses or with chemotherapy.

Factors Involved in Preoperative Edema in High-Grade Gliomas.

Background Expansion of preoperative edema (PE) is an independent poor prognostic factor in high-grade gliomas. Evaluation of PE provides important information that can be readily obtained from magnetic resonance imaging (MRI), but there are few reports on factors associated with PE. The goal of this study was to identify factors contributing to PE in Grade 3 (G3) and Grade 4 (G4) gliomas. Methodology PE was measured in 141 pathologically proven G3 and G4 gliomas, and factors with a potential relationship with PE were examined in univariate and multivariate analyses. The following eight explanatory variables were used: age, sex, Karnofsky performance status (KPS), location of the glioma, tumor diameter, pathological grade, isocitrate dehydrogenase (IDH)-1-R132H status, and Ki-67 index. Overall survival (OS) and progression-free survival (PFS) were calculated in groups divided by PE (<1 vs. ≥1 cm) and by factors with a significant correlation with PE in multivariate analysis. Results In univariate analysis, age (p = 0.013), KPS (p = 0.012), pathology grade (p = 0.004), and IDH1-R132H status (p = 0.0003) were significantly correlated with PE. In multivariate analysis, only IDH1-R132H status showed a significant correlation (p = 0.036), with a regression coefficient of -0.42. The median follow-up period in survivors was 38.9 months (range: 1.2-131.7 months). The one-, two-, and three-year OS rates for PE <1 vs. ≥1 cm were 77% vs. 68%, 67% vs. 44%, and 63% vs. 24% (p = 0.0001), respectively, and those for IDH1-R132H mutated vs. wild-type cases were 85% vs. 67%, 85% vs. 40%, and 81% vs. 21% (p < 0.0001), respectively. The one-, two-, and three-year PFS rates for PE <1 vs. ≥1 cm were 77% vs. 49%, 64% vs. 24%, and 50% vs. 18% (p = 0.0002), respectively, and those for IDH1-R132H mutated vs. wild-type cases were 85% vs. 48%, 77% vs. 23%, and 73% vs. 14% (p < 0.0001), respectively. Conclusions IDH1-R132H status was found to be a significant contributor to PE. Cases with PE <1 cm and those with the IDH1-R132H mutation clearly had a better prognosis.

Light flash and odor during proton beam therapy for pediatric patients: a prospective observational study.

Light flash and odor during radiation therapy are well-known phenomena, but the details are poorly understood, particularly in pediatric patients. Therefore, we conducted a prospective observational study of these events in pediatric patients (age ≤20 years old) who received radiotherapy at our center from January 2019 to November 2021. Light flash and odor were evaluated using a patient-reported checklist including the presence, strength, and duration of the phenomenon, and color of light or type of odor. 53 patients who received proton therapy (n=47) and photon radiotherapy (n=6) were enrolled in this study. The median age of the patients was 10, ranged from 5 to 20. The patients who was able to see the light flash was 4, and all of them received retina irradiation. This was equivalent to 57% of the patients who received radiotherapy to retina (n=7). The light was bright and colored mainly blue and purple, which seemed to be consistent with Cherenkov light. Odor was sensed by 9 (17%) patients, and seven patients of the 9 received nasal cavity irradiation. This was equivalent to 41% of the patients who received nasal cavity irradiation (n=17). Other 2 patients received proton therapy to brain tumor. The odors were mainly described as plastic, burnt and disinfectant, which may be caused by ozone generated during irradiation. These data suggest that pediatric patients with retinal and nasal cavity irradiation frequently sense light flashes or odor. So adequate care is necessary so that these patients are not worried about this phenomenon.

Abnormal sensation during total body irradiation: a prospective observational study.

Light flash and odor during radiotherapy are well-known phenomena. Two prospective observational studies have indicated that 55% of patients observed a light flash during irradiation of the retina and 27% of patients sensed an odor during radiotherapy for the nasal cavity. A prospective observational study was performed in all patients at our hospital who received total body irradiation (TBI) between January 2019 to October 2021. Light flash and odor during TBI were examined using the same method as that used in previous studies. A total of 32 patients received TBI during the study period. The patients had a median age of 41 (18-60) years, and included 20 males and 12 females. A survey checklist showed that 14 patients (44%) sensed light and 14 patients (44%) sensed odor during TBI,. The color of the light during irradiation was yellow in six cases, white in four cases, and blue in four cases. The intensity of the light was 2-5 (median 3, 1 is very weak, 5 is very strong) and the time over which the light flash was felt was 4-60 s (median 10 s). Two patients each sensed smells of plastic, ozone and bleach, and others sensed one smell each. The intensity of the odor was 1-4 (median 3, 1 is very weak, 5 is very strong) and the time over which the odor was sensed was 1-25 s (median 3 s). We conclude that light flashes and odors are each sensed by 44% of patients during TBI. Various types of light flashes and odors were reported in this study.

Proton Beam Therapy in Elderly Patients With cT1-3N0M0 Non-small Cell Lung Cancer.

BACKGROUND/AIM: To investigate the outcomes of elderly patients with cT1-3N0M0 non-small cell lung cancer (NSCLC) undergoing proton beam therapy (PBT). PATIENTS AND METHODS: Between 2009 and 2019, 110 patients receiving hypofractionated PBT for cT1-3N0M0 NSCLC were retrospectively reviewed. RESULTS: The median follow-up was 36.5 months (range=4.9-131.0 months). In the elderly group (80 years or older), the 3-year overall survival and progression-free survival rates were 79.8% and 73.9%, respectively, and the corresponding rates in the younger group were 80.5% and 61.2%, respectively. Grade 3 radiation pneumonitis (RP) was observed in 4.4% patients in the young group, whereas no grade 3 RP was observed in the elderly group. Age was not a risk factor for symptomatic RP. There were no significant differences in the survival and adverse events between the elderly and younger groups. CONCLUSION: PBT may be a reasonable approach for treating lung cancer in elderly patients with T1-3N0M0 NSCLC.

Olfactory Sensations During Proton and Photon Radiotherapy: A Multicenter Prospective Observational Study.

PURPOSE: Patients often report a sense of smell during radiation therapy (RT), but the details of these events are not well understood. The purpose of the study was to evaluate events of smell during photon RT and proton beam therapy (PBT). METHODS AND MATERIALS: The subjects were all adult patients (≥20 years old) treated with photon RT or PBT at two centers from January 2019 to August 2020, with the exclusion of those with communication difficulties or olfactory abnormality. The presence of smell, odor type, intensity (five levels), and time period was examined prospectively using a weekly checklist. RESULTS: A total of 649 courses were examined in 620 patients who received photon RT (n=415) or PBT (n=205). A smell during the procedure was sensed by 51 patients (8.2%). In multivariate logistic regression analysis, nasal cavity dose (p=0.002), age (p<0.001), and photon RT (p=0.018) were identified as significant factors associated with a sense of smell. Smell occurred in only 23/515 patients (4.5%) in whom the nasal cavity was not irradiated, but in 4/19 (21.1%) and 24/86 (27.9%) with nasal cavity maximum isodose lines of 10%-50% and 60%-100%, respectively. Patients who received photon RT sensed a smell (43/415; 10.4%) more frequently than those treated with PBT (8/205; 3.9%). Of the 51 patients who sensed a smell, 32 (63%) reported a burnt smell, eight (16%) a chemical smell, two (4%) a sour smell, and nine another smell (copier machine, sweet, garbage, etc.). CONCLUSIONS: The sense of a smell appears to be common during RT and this sensation is significantly associated with the nasal cavity dose, younger age, and photon RT.

Light flashes during proton and photon radiotherapy: A multicenter prospective observational study.

BACKGROUND: Patients who receive radiation therapy sometimes complain of a light flash during irradiation. The details of the characteristics of this light have not been described. PURPOSE: To evaluate light flashes during photon and proton radiotherapy. METHODS AND MATERIALS: A prospective observational study was performed in all adult patients (≥20 years old) who received photon and proton therapy at two centers between January 2019 and August 2020, except for patients who could not communicate and those with visual abnormality. Evaluations were obtained for the presence or absence of light flashes, light darkness (7 levels), light intensity (5 levels), frequency, light movement, light flashing, and time seeing the light, using a weekly checklist. RESULTS: A total of 650 courses were examined for 621 patients, of whom 416 received photon radiotherapy and 205 received proton beam therapy. The checklist indicated that 88 patients (16.1%) sensed light during photon or proton radiotherapy. In multivariate logistic regression analysis, the factors that were significantly associated with a light flash were a higher retina dose and younger age (p < 0.001). Light flashes were seen by only 35/524 patients (6.7%) for whom the retina was not irradiated, but by 13/33 (39.4%) and 41/64 (64.1%) with maximum isodose lines for the retina of 10-50% and 60-100%, respectively. The numbers of patients who sensed blue, purple, yellow, red, white and other colors were 52, 15, 15, 9, 16 and 8, respectively (multiple selections possible). Light movement was observed by 52 patients (59%). The location of the light was defined as near, far, and middle by 70, 13, and 5 patients, respectively. The median time the light was seen was 10 s. CONCLUSIONS: Many patients sense light flashes during radiotherapy. The retina dose and a younger age were significantly associated with the frequency of light flashes.

The impact of lymphopenia during chemoradiotherapy using photons or protons on the clinical outcomes of esophageal cancer patients.

We assessed the development of lymphopenia during concurrent chemoradiotherapy (CRT) using X-ray versus proton beams and the impact on survival in patients with esophageal cancer. Among patients with esophageal cancer who were administered concurrent CRT with a curative intent at our institute from 2014 to 2018, 69 (15 receiving X-ray radiotherapy (XRT) and 54 receiving proton beam therapy [PBT]) who underwent weekly blood testing during treatment were enrolled. The absolute lymphocyte counts (ALC) at 1, 5 and 6 weeks were significantly higher in the patients who received PBT than in those who received XRT (p = 0.002, p = 0.006 and p = 0.009, respectively), and a similar trend in the neutrophil-to-lymphocyte ratio (NLR) was observed (p = 0.003 at 5 weeks). The 2-year overall survival (OS) and progression-free survival (PFS) rates tended to be higher in the patients who maintained an ALC ≥200 compared with those who did not (p = 0.083 and p = 0.053, respectively), and similar trends were observed in the NLR (p = 0.061 and p = 0.038, respectively). Dose-volume analysis revealed significant correlations between volumes of the thoracic bones irradiated by 5-50 Gy and minimum ALCs and maximum NLR. These findings suggested that PBT prevented the development of lymphopenia during CRT by reducing the irradiated volume of the thoracic bone, and the maintained lymphocyte count is possibly one of the early predictors for survival in patients with esophageal cancer.

Risk factor of pneumonitis on dose-volume relationship for chemoradiotherapy with durvalumab: Multi-institutional research in Japan.

OBJECTIVES: To estimate appropriate dose-volume parameters for avoidance of pneumonitis in use of chemoradiotherapy and durvalumab for treatment of lung cancer. MATERIALS AND METHODS: Patients with non-small cell lung cancer treated with concurrent chemoradiotherapy followed by durvalumab at 9 centers were enrolled in the study. Three-dimensional radiotherapy, intensity modulated radiotherapy, and proton beam therapy were used. The frequency and severity of pneumonitis and the dose-volume relationship for normal lung were evaluated. Univariable and multivariable analyses were conducted to identify risk factors. A covariate adjusted hazard ratio was then estimated for the percentages of normal lung volume irradiated at ≥ X Gy (Vx) (X = 5-40) and lung volume non-irradiated at ≥ X Gy (X = 5-40), with the covariates selected in the variable selection. Cumulative incidence functions and covariate adjusted hazard ratios were also estimated for dichotomized variables, with estimated cut-off points. RESULTS: A total of 91 patients were enrolled in the study. The median time from the start of radiotherapy to development of pneumonitis was 4.1 months. Pneumonitis was observed in 80 patients (88%), including grade 2 or severe pneumonitis in 31 (34%) and ≥ grade 3 pneumonitis in 11 (12%). Pneumonitis was inside the irradiation field in 73 of the 80 patients (91%). The selected factors for ≥ grade 2 pneumonitis were V20, and primary site (upper lobe) in multivariable analysis. The cut off value of V20 was 18.99%, and there was a significant difference between V20 of < 18.77 and ≥ 18.77. CONCLUSION: Though there are some limitation of this study, the basic concept of concurrent chemoradiotherapy with an emphasis on V20 remains unchanged in use of durvalumab. However, we recommend reduction of V20 to as small a value as possible in use of this therapy.

Transitions of Liver and Biliary Enzymes during Proton Beam Therapy for Hepatocellular Carcinoma.

Proton beam therapy (PBT) is a curative treatment for hepatocellular carcinoma (HCC), because it can preserve liver function due to dose targeting via the Bragg peak. However, the degree of direct liver damage by PBT is unclear. In this study, we retrospectively analyzed liver/biliary enzymes and total bilirubin (T-Bil) as markers of direct liver damage during and early after PBT in 300 patients. The levels of these enzymes and bilirubin were almost stable throughout the treatment period. In patients with normal pretreatment levels, aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), and T-Bil were abnormally elevated in only 2 (1.2%), 1 (0.4%), 0, 2 (1.2%), and 8 (3.5%) patients, respectively, and in 8 of these 13 patients (61.5%) the elevations were temporary. In patients with abnormal pretreatment levels, the levels tended to decrease during PBT. GGT and T-Bil were elevated by 1.62 and 1.57 times in patients who received 66 Gy (RBE) in 10 fractions and 74 Gy (RBE) in 37 fractions, respectively, but again these changes were temporary. These results suggest that direct damage to normal liver caused by PBT is minimal, even if a patient has abnormal pretreatment enzyme levels.