Radiation­induced pleomorphic liposarcoma after hypofractionated radiotherapy following breast­conserving surgery: A case report and literature review.

Breast cancer is one of the leading causes of cancer globally. Radiotherapy following breast-conserving surgery is the standard treatment of breast cancer. Recently, hypofractionated irradiation comprising 42.56 Gy in 16 fractions was selected as a viable radiation therapeutic option. Radiation-induced sarcoma is the most prevalent secondary malignancy in patients undergoing radiotherapy after breast cancer surgery. Angiosarcomas are the predominant type of radiation-induced sarcomas, whereas liposarcomas have rarely been reported. The present report details an uncommon instance of radiation-induced pleomorphic liposarcoma that occurred 8 years after breast-conserving surgery and hypofractionated radiotherapy. The patient visited the hospital due to hardening of the tissue beneath the skin of the right breast. Ultrasonography revealed a hypoechoic mass in the lower part of the right breast containing internal blood flow. An excisional biopsy revealed that the tumor contained infiltrating spindle-shaped cells without a capsule containing pleomorphic cells. Lipoblasts were also observed and tended to differentiate into adipose tissue, leading to a diagnosis of pleomorphic liposarcoma. Immunostaining revealed negativity for cytokeratin AE1/AE3, ERG, MDM2 and S-100 protein; the Ki-67 index was ~20%. An enlargement resection involving a postoperative bed was performed because of close tumor margins. 18F-fluorodeoxyglucose positron emission tomography/computed tomography revealed pale accumulation of 18F-fluorodeoxyglucose in the right chest wall, which was interpreted as a postoperative change owing to the resection biopsy. The tumor was observed in the irradiated field with no distant metastases. Following extensive resection, the patient maintained a recurrence-free survival period of 3 years and 2 months, during which no adjuvant therapy was administered. Therefore, follow-up is necessary in patients with breast cancer treated with radiotherapy.

Impact of the neutrophil-to-lymphocyte ratio on patients with locally advanced non-small cell lung cancer who suffer radiation pneumonitis during the course of induction chemoradiotherapy followed by surgery.

PURPOSE: Radiation pneumonitis (RP) is an obstacle for patients after surgery following induction chemoradiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC). We performed a comparative analysis of the association between clinicopathological factors, including the neutrophil-to-lymphocyte ratio (NLR) and prognosis, in LA-NSCLC patients with or without RP during induction chemoradiotherapy followed by surgery. METHODS: The subjects of this analysis were 168 patients undergoing trimodality therapy for LA-NSCLC between January, 1999 and May, 2019. Patients were divided into two groups: the RP group (n = 41) and the non-RP group (n = 127). We compared the clinicopathological factors including the NLR between the groups and analyzed the association between the NLR and prognosis. RESULTS: The RP group had more patients with tumors located in the lower lobe, more bilobar resections, shorter operative times, no implementation of postoperative adjuvant chemotherapy, and a higher postoperative NLR than the non-RP group. There were no significant differences in serious postoperative complications and the prognosis. Patients with a low postoperative NLR had a significantly better prognosis in the non-RP group, and a trend toward a better prognosis even in the RP group. CONCLUSION: Postoperative NLR may be a useful prognostic factor, even for patients who suffer RP after trimodality therapy for LA-NSCLC.

Long-term outcomes of salvage transurethral high-dose-rate brachytherapy combined with external beam radiation therapy for anastomotic recurrence of prostate cancer after radical prostatectomy: A retrospective analysis.

BACKGROUND: High-dose-rate brachytherapy (HDR-BT) delivers high-dose radiation to local lesions within a short treatment period. There are no reports of salvage transurethral HDR-BT for biochemical recurrence (BCR) after radical prostatectomy. Thus, we aimed to evaluate the usefulness of salvage transurethral HDR-BT with external beam radiation therapy (EBRT) for anastomotic prostate cancer recurrence. METHODS AND MATERIALS: Patients with postoperative prostate cancer who underwent salvage transurethral HDR-BT with EBRT for anastomotic recurrence at our hospital between January 2002 and July 2009 were retrospectively evaluated. The Kaplan-Meier method was used to estimate biochemical freedom from failure (bFFF), cause-specific survival (CSS), and overall survival (OS) rates. RESULTS: Nine patients were included in this study. The median follow-up period and age were 13.1 (range 4.3-18.4) years and 67 (range 63-78) years, respectively. The dose of HDR-BT ranged from 13 to 24 Gy per 2 to 5 fractions, while that of EBRT ranged from 30 to 44 Gy per 15 to 22 fractions. The 1-year, 5-year, and 10-year bFFF rates were 77.8%, 41.7%, and 13.9%, respectively. The 10-year and 15-year CSS rates were 100% each. The 10-year and 15-year OS rates were 100% and 64.3%, respectively. Six patients were diagnosed with BCR. Two patients experienced Grade 3 hematuria as a late adverse event. There was no exacerbation of urinary incontinence. CONCLUSIONS: No prostate cancer-related deaths were observed, even after a long-term follow-up. Salvage transurethral HDR-BT after radical prostatectomy is safe and feasible and may be a useful treatment option.

Spinal Instability as a Prognostic Factor in Patients With Spinal Metastasis of Castration-resistant Prostate Cancer.

BACKGROUND/AIM: To evaluate the Spinal Instability Neoplastic Score (SINS) for prediction of survival in patients with spinal column metastasis of castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: A retrospective study of spinal instability was performed in patients with CRPC using SINS. Overall survival was evaluated starting from the time of SINS evaluation. The subjects were 42 patients with CRPC among 261 cases diagnosed with metastatic spinal tumors by radiologists, among 42,152 cases that underwent a body computed tomography scan at Kawasaki Medical School Hospital within 32 months from December 2013 to July 2016. RESULTS: The median age was 78 (range=55-91 years), the median prostate-specific antigen (PSA) level at SINS evaluation was 42.1 (0.1-3,121.6) ng/ml, and 11 patients had visceral metastasis. The median periods from diagnosis of bone metastasis and development of CRPC to SINS evaluation were 17 (0-158) and 20 (0-149) months, respectively. The spine was stable in 32 cases (group S) and potentially unstable or unstable in 10 (24%) (group U). The median observation period was 17.5 (0-83) months and 36 patients died. The median survival period after SINS evaluation was longer in group S than that in group U (20 vs. 10 months, p=0.0221). In multivariate analysis, PSA level, visceral metastasis, and spinal instability were significant prognostic factors. The hazard ratio for patients in group U was 2.60 (95%CI=1.07-5.93, p=0.0345). CONCLUSION: Spinal stability evaluated using SINS is a new prognostic factor for survival of patients with spinal metastasis of CRPC.

Feasibility of magnetic resonance imaging-ultrasound guided high-dose-rate brachytherapy for localized prostate cancer: Preliminary results from a prospective study.

OBJECTIVE: This study aimed to investigate preliminary outcomes of a prospective trial of magnetic resonance imaging-ultrasound fusion-guided ultrafocal high-dose-rate brachytherapy in localized prostate cancer. METHODS: In our prospective study, data from patients who underwent this treatment between April 1, 2020 and March 31, 2021 were analyzed. In the procedure, the applicator needle was inserted through the perineum to target the lesion on the multiparametric magnetic resonance imaging, which was fused onto the transrectal ultrasound image. The prescription dose was set at a single fraction of 19 Gy. Data from patients who received whole-gland high-dose-rate brachytherapy were extracted and compared with data from patients who received ultrafocal high-dose-rate brachytherapy, to evaluate the frequency of acute adverse events. RESULTS: Eight patients underwent ultrafocal high-dose-rate brachytherapy with a median observation period of 7.75 months (range 5.96-15.36 months). No acute genitourinary or gastrointestinal adverse events were observed in this cohort. The planned procedure was completed in all patients, and no unexpected adverse events were observed; however, prostate-specific antigen failure was detected in one patient. In the 25 patients who underwent whole-gland high-dose-rate brachytherapy, acute genitourinary and gastrointestinal adverse events were observed in 88% and 20% of the patients, respectively. Ultrafocal high-dose-rate brachytherapy was a significant factor in avoiding acute adverse genitourinary events in univariate and multivariate analyses (P < 0.001 and P = 0.032, respectively). CONCLUSIONS: Magnetic resonance imaging-ultrasound fusion-guided ultrafocal high-dose-rate brachytherapy in localized prostate cancer is a safe and feasible treatment without acute genitourinary and gastrointestinal adverse events. Long-term observation and further investigation are warranted.

Proton beam therapy followed by pembrolizumab for giant ocular surface conjunctival malignant melanoma: A case report.

The present study describes proton beam therapy as a clinical option to achieve local control of giant conjunctival melanoma in an aged person, instead of orbital exenteration. An 80-year-old woman with one-year history of left-eye injection and hemorrhage experienced rapid growth of the ocular surface black mass. At the initial visit, a black, elastic hard, hemorrhage-prone, thickened mass in the size of 30x40 mm with a presumed wide stalk covered the total area of the lid fissure on the left side. Biopsy of the mass demonstrated anomalous melanin-containing cells in fibrin and hemorrhage, which were positive for cocktail-mix antibodies against tyrosinase, melanoma antigen recognized by T cells-1 and human melanoma black-45, indicative of malignant melanoma. One month after the initial visit, the patient underwent proton beam therapy at the total dose of 70.4 Gy (relative biological effectiveness) in 32 fractions (~10 min each) in one and a half months. One month after the end of proton beam therapy, 3.5 months from the initial visit, the patient was found by computed tomographic scan to have multiple metastatic lesions in bilateral lung fields. With the evidence of absent BRAF mutation, the patient underwent intravenous administration of pembrolizumab 77.2 mg every three weeks five times in total. Then, three months after proton beam therapy, ocular surface melanoma almost subsided and the clear cornea allowed visualization of the intraocular lens inside the eye. In three weeks, spontaneous corneal perforation was plugged with iris incarceration. The patient died suddenly of unknown cause 7.5 months from the initial visit. The local control of giant conjunctival melanoma was achieved by proton beam therapy, leading to patient's satisfaction and better quality of life. Proton beam therapy, followed by immune checkpoint inhibitors, would become the future standard of care for unresectable giant conjunctival melanoma.

New field-in-field with two reference points method for whole breast radiotherapy: Dosimetric analysis and radiation-induced skin toxicities assessment.

The usefulness of the field-in-field with two reference points (FIF w/ 2RP) method, in which the dose reference points are set simultaneously at two positions in the irradiation field and the high-dose range is completely eliminated, was examined in the present study with the aim of decreasing acute skin toxicity in adjuvant breast radiotherapy (RT). A total of 573 patients with breast cancer who underwent postoperative whole breast RT were classified into 178 cases with wedge (W) method, 142 cases with field-in-field without 2 reference points (FIF w/o 2RP) method and 253 cases with FIF w/ 2RP method. Using the FIF w/ 2RP method, the high-dose range was the lowest among the three irradiation methods. The planning target volume (PTV) V105% and the breast PTV for evaluation (BPe) V105% decreased to 0.09 and 0.10%, respectively. The FIF w/ 2RP method vs. the FIF w/o 2RP method had a strong association (η) with PTV V105% (η=0.79; P<0.001) and BPe V105% (η=0.76; P<0.001). The FIF w/ 2RP method had a significant impact on lowering the skin toxicity grade in weeks 3 and 4, and increasing the occurrence of skin toxicity grade 0. The FIF w/ 2RP method vs. the W method had a moderate association with skin toxicity grade at week 3 (η=0.49; P<0.001). Using the FIF w/ 2RP method, the high-dose range V105% of the target decreased to 0%, and skin adverse events were decreased in conjunction. For patients with early-stage breast cancer, particularly patients with relatively small-sized breasts, the FIF w/ 2RP method may be an optimal irradiation method.

Clinical Outcome of Palliative Concurrent Chemoradiotherapy with Cisplatin/Docetaxel for Stage III Non-small Cell Lung Cancer.

Palliative concurrent chemoradiotherapy (CCRT) is often administered to patients with stage III non-small cell lung cancer (NSCLC). We investigated the clinical outcomes of patients receiving palliative CCRT for NSCLC. Data of patients with NSCLC who underwent palliative CCRT (n=16), preoperative CCRT plus surgery (n=97), or definitive CCRT (n=48) were evaluated. In all groups, the concurrent chemotherapy regimens consisted of cisplatin and docetaxel. Rates of local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and prognosis were compared. The 2-year rates of LC, DMFS, PFS, and OS in 16 patients who underwent palliative CCRT were 44.4%, 12.5%, 12.5%, and 18.8%, respectively. Univariate analysis showed that palliative CCRT was associated with poor LC (p<0.001), DMFS (p<0.001), PFS (p<0.001), and OS (p<0.001) outcomes in patients who completed CCRT as a preoperative treatment and poor LC (p=0.01), DMFS (p=0.003), PFS (p=0.04), and OS (p=0.004) outcomes in patients who were considered for definitive CCRT. Although there were some long-term survivors, the clinical outcomes of palliative CCRT were significantly inferior to those of the ideal treatments. Therefore, careful determination of the appropriate treatment indications and further studies are warranted.

Investigation into the Effect of Breast Volume on Irradiation Dose Distribution in Asian Women with Breast Cancer.

Reports on irradiation dose distribution in breast cancer radiotherapy with sufficient sample size are limited in Asian patients. Elucidating dose distribution in Asian patients is particularly important as their breast volume differs compared to patients in Europe and North America. Here, we examined dose distribution in the irradiation field relative to breast volume for three irradiation methods historically used in our facility. We investigated the influence of breast volume on each irradiation method for Asian women. A total of 573 women with early-stage breast cancer were treated with breast-conserving surgery and adjuvant radiotherapy. Three methods were compared: wedge (W), field-in-field (FIF), and wedge-field-in-field (W-FIF). In patients with small breast volume, FIF decreased low- and high-dose areas within the planning target volume, and increased optimal dose area more than W. In patients with medium and large breast volumes, FIF decreased high-dose area more than W. The absolute values of correlation coefficients of breast volume to low-, optimal-, and high-dose areas and mean dose were significantly lower in FIF than in W. The correlation coefficients of V107% were 0.00 and 0.28 for FIF and W, respectively. FIF is an excellent irradiation method that is less affected by breast volume than W in Asian breast cancer patients.

Phase I dose-escalation study of endoscopic intratumoral injection of OBP-301 (Telomelysin) with radiotherapy in oesophageal cancer patients unfit for standard treatments.

PURPOSE: OBP-301 (Telomelysin) is an attenuated type-5 adenovirus that contains the human telomerase reverse transcriptase promoter to regulate viral replication. OBP-301 sensitises human cancer cells to ionising radiation by inhibiting DNA repair, and radiation enhances coxsackievirus and adenovirus receptor-mediated OBP-301 infection on the contrary. We assessed OBP-301 with radiotherapy in oesophageal cancer patients unfit for standard chemoradiation treatments. METHODS: A phase I dose-escalation study of OBP-301 with radiotherapy was conducted in 13 histologically confirmed oesophageal cancer patients deemed unfit to undergo surgery or chemotherapy. Study treatment consisted of OBP-301 administration by intratumoural needle injection using a flexible endoscope on days 1, 18 and 32. Radiotherapy was administered concurrently over 6 weeks, beginning on day 4, to a total of 60 Gy. RESULTS: Of the 13 patients, 7, 3 and 3 patients were treated with 1010, 1011 and 1012 virus particles, respectively. Study group comprised 10 males and 3 females, with a median age of 82 years (range, 53-91 years). All patients developed a transient, self-limited lymphopenia. Distribution studies revealed transient virus shedding in the plasma. Eight patients had local complete response (CR); all of them exhibited no pathologically viable malignant cells in biopsy specimens, and 3 patients had a partial response. The objective response rate was 91.7%. The clinical CR rate was 83.3% in stage I and 60.0% in stage II/III. Histopathological examination revealed massive infiltration of CD8+ cells and increased PD-L1 expression. CONCLUSION: Multiple courses of endoscopic intratumoural OBP-301 injection with radiotherapy are feasible and provide clinical benefits in patients with oesophageal cancer unfit for standard treatments.

Sarcopenia is associated with poor prognosis after chemoradiotherapy in patients with stage III non-small-cell lung cancer: a retrospective analysis.

We intended to investigate whether muscle and adipose masses were associated with prognosis among patients with stage III non-small-cell lung cancer (NSCLC) who were undergoing chemoradiotherapy (CCRT). We retrospectively explored data of patients with stage III NSCLC who underwent definitive CCRT (≥ 60 Gy) between January 2004 and March 2018 at our hospital. We examined the relationship of overall survival (OS) with body mass index (BMI), skeletal muscle index (SMI), psoas muscle index (PMI), visceral adipose tissue index (VAI), subcutaneous adipose tissue index (SAI), and visceral-to-subcutaneous adipose tissue area ratio (VSR) using log-rank tests for the univariate analysis and Cox proportional hazard models for the multivariate analysis. Overall, 16, 32, and 12 patients had stage IIIA, IIIB, and IIIC NSCLC, respectively. The total radiotherapy dose ranged from 60 Gy/30 fractions to 66 Gy/33 fractions. In the univariate analysis, the performance status (PS), BMI, and SMI were associated with OS, whereas the PMI, VAI, SAI, and VSR were not. In the multivariate analysis, the PS and SMI were associated with OS. The hazard ratios and 95% confidence intervals were 2.91 and 1.28-6.64 for PS, and 2.36 and 1.15-4.85 for SMI, respectively. The 1, 3, and 5-year OS rates were 92.1%, 59.6%, and 51.0% in patients with high SMI, and 63.6%, 53.8%, and 17.9% in patients with low SMI, respectively. The SMI correlated with prognosis in our study population, whereas adipose mass did not. Therefore, sarcopenia should be considered while predicting the OS in such patients.

Sarcopenia is related to poor prognosis in patients after trimodality therapy for locally advanced non-small cell lung cancer.

BACKGROUND: The association between sarcopenia and prognosis in patients with locally advanced non-small cell lung cancer (NSCLC) undergoing trimodality therapy, consisting of preoperative concurrent chemoradiotherapy and surgery, has not been reported. Therefore, we aimed to investigate the association of sarcopenia and fat mass with prognosis after trimodality therapy. METHODS: To assess sarcopenia, the psoas muscle mass was measured. Using computed tomography data, including third lumbar vertebra level images, psoas muscle mass and visceral and subcutaneous fat mass were measured. Additionally, body mass indices, and visceral/subcutaneous fat ratio, obtained by dividing the visceral fat index by the subcutaneous fat index, were calculated. We investigated the relationship between these parameters and overall survival. RESULTS: Ninety-nine eligible patients were included. In the univariate analysis, age, clinical stage, tumor location, psoas muscle index, and visceral/subcutaneous fat ratio were significant prognostic factors for overall survival (P = 0.008, P = 0.04, P = 0.04, P = 0.02, and P = 0.02, respectively). In the multivariate analysis, age and psoas muscle index were significant prognostic factors for overall survival (P = 0.01 and P = 0.03, respectively). The 5-year overall survival rates for the high and low psoas muscle index groups were 79.6% [95% confidence interval (CI), 67.1-94.5%] and 66.2% (95% CI, 54.1-81.1%), respectively; whereas, the 10-year overall survival rates were 61.9% (95% CI, 42.0-91.4%) and 25.3% (95% CI, 8.6-74.2%), respectively. CONCLUSION: Sarcopenia was related to poor overall survival in patients with locally advanced NSCLC undergoing trimodality therapy. Assessment of body composition prior to treatment may provide important information for formulating rational therapeutic strategies.

A randomized trial of sodium alginate prevention of esophagitis in LA-NSCLC receiving chemoradiotherapy: OLCSG1401.

BACKGROUND: Radiation esophagitis is a critical adverse event that needs to be appropriately managed while administering thoracic irradiation. This trial aimed to investigate whether sodium alginate has preventative effects on esophagitis in patients with non-small-cell lung cancer (NSCLC) receiving concurrent chemoradiotherapy (CRT). METHODS: Patients with untreated stage III NSCLC who were eligible for concurrent CRT were randomly assigned at a 1:1:1 ratio to receive one of the following treatments: initial or late use of oral sodium alginate (arms A and B) or water as control (arm C). The primary endpoint was the proportion of patients developing G3 or worse esophagitis. RESULTS: Overall, 94 patients were randomly assigned between February 2014 and September 2018. The study was prematurely terminated because of slow accrual. The proportions of patients with G3 or worse esophagitis were 12.5%, 9.8%, and 19.4% in arms A, B, and C, respectively. Patients receiving sodium alginate had fewer onsets of G3 esophagitis; however, differences compared with arm C were not significant (A vs. C: p = 0.46; B vs. C: p = 0.28). The rates of grade 3 or worse non-hematologic toxicities besides esophagitis were 29%, 26%, and 43% in arms A, B, and C, respectively. Interestingly, compared with arm C, a low rate of febrile neutropenia was observed in arm A (3.1% vs. 19.4%: p = 0.04). CONCLUSIONS: Sodium alginate did not show significant preventative effects on radiation-induced esophagitis in patients with NSCLC. The frequency of CRT-induced febrile neutropenia was lower in the early use sodium alginate arm. TRIAL REGISTRATION: ClinicalTrials.gov Identifier Registry number: UMIN000013133.

A PET/CT volumetric parameter predicts prognosis of non-small cell lung cancer treated using preoperative chemoradiotherapy and surgery: A retrospective case series study.

The purpose of the present study was to clarify whether positron emission tomography/computed tomography (PET/CT) volumetric parameters were prognostic predictors of non-small cell lung cancer (NSCLC) treatment in patients who had undergone preoperative concurrent chemoradiotherapy (CCRT) and surgery. In the present study, retrospectively surveyed the data of patients with NSCLC who underwent preoperative CCRT and surgery at Okayama University Hospital (Okayama, Japan) between April 2006 and March 2018. The maximum standardized uptake value (SUVmax) and volumetric parameters, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were calculated using PET/CT and the percentage decrease (Δ) in each parameter value post-CCRT. The SUVmax threshold for defining MTV was set at 2.5. Furthermore, the association between survival and PET parameter values was analyzed. A total of 52 patients were included in the present study. The median follow-up period was 50.65 months. In univariate analysis, ΔTLG was identified to be a significant predictor of progression-free survival (PFS; P=0.03). The 5-year PFS rates were 48.6 and 76.6% for patients with low ΔTLG and high ΔTLG, respectively. High ΔTLG was indicative of a higher overall survival rate (P=0.08). The present results suggest that ΔTLG calculated using PET/CT is a prognostic predictor of NSCLC treated using preoperative CCRT and surgery, and may help physicians determine treatment strategies.

Volumetric PET Parameters Predict Prognosis after Definitive Chemoradiotherapy with Cisplatin/Docetaxel for Stage III Non-Small Cell Lung Cancer.

The aim of this study was to investigate whether volumetric positron emission tomography (PET) parameters are prognostic predictors in stage III non-small cell lung cancer patients receiving definitive concurrent chemo-radiotherapy (CCRT) with cisplatin/docetaxel. Cases involving definitive CCRT were reviewed retrospectively, and the maximum standardized uptake value, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. The relationships between these PET parameters and prognosis were analyzed. MTV and TLG were significant predictors of distant metastasis-free survival (DMFS) (p = 0.0003 and 0.0005, respectively) and progression-free survival (PFS) (p = 0.001 and 0.0007, respectively). The three-year DMFS rates in patients with low and high MTV were 13.3% and 64.6%, respectively, and the corresponding values in those with low and high TLG were 13.3% and 65.2%, respectively. The three-year PFS rates in patients with low and high MTV were 13.3% and 57.8%, respectively, and the corresponding values in patients with low and high TLG were 13.3% and 57.8%, respectively. However, MTV and TLG were not predictors of local control or overall sur-vival. We demonstrated that volumetric PET parameters were predictors of patients receiving definitive CCRT. Our findings contradict the findings of previous reports and warrant further research to validate them.

Lung stereotactic body radiation therapy for elderly patients aged ≥ 80 years with pathologically proven early-stage non-small cell lung cancer: a retrospective cohort study.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is an established therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC). Many elderly patients are medically inoperable owing to comorbidities. Therefore, SBRT may be a useful therapy for elderly patients. However, the application of SBRT for patients aged ≥ 80 years has not been completely elucidated. Therefore, this study aimed to assess the clinical utility of SBRT for elderly patients aged ≥ 80 years with pathologically proven early-stage NSCLC. METHODS: We retrospectively evaluated the data of patients aged ≥ 80 years with pathologically proven primary NSCLC who underwent SBRT at our institution between January 2009 and March 2020. Treatment outcomes and toxicities were analyzed. We used the Kaplan-Meier method to estimate survival curves and the log-rank test to compare the survival curves. We performed univariate and multivariate Cox regression analyses. p-values < 0.05 were regarded significant. RESULTS: Sixty-four patients (65 lesions) were included, and the median follow-up period was 38.7 (range 3.5-95.7) months. The median age was 82.9 (range 80.0-94.8) years. Sixteen patients were medically operable, and 48 patients were medically inoperable. The prescribed dose of SBRT was either 48 Gy in four fractions or 60 Gy in 10 fractions. The median survival time was 60.0 months (95% confidence interval, 43.5-71.1). The 1-, 3-, and 5-year local control, cancer-specific survival, progression-free survival, and overall survival rates were 98.4%, 98.4%, 81.0%, and 88.9%; 90.1%, 93.7%, 58.9%, and 68.3%; and 87.4%, 83.5%, 38.2%, and 47.5%, respectively. Multivariate analysis revealed that inoperability and solid nodules were the predictors of poor overall survival after SBRT in elderly patients. Two patients (3.1%) had grade 3 radiation pneumonitis, and one patient (1.6%) had grade 5 radiation pneumonitis. CONCLUSIONS: SBRT was feasible in patients aged ≥ 80 years with NSCLC. It achieved good local control with minimal toxicity. SBRT may be beneficial in elderly patients with early-stage NSCLC.

Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Locally Advanced Non-small-cell Lung Cancer Treated with Trimodality Therapy.

PURPOSE: Current evidence suggests that the neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor in several types of cancer. In this study, we aimed to evaluate the prognostic impact of clinicopathological factors, including postoperative NLR, in patients with locally advanced non-small-cell lung cancer (LA-NSCLC) who underwent surgery after chemoradiotherapy (CRT) with or without postoperative adjuvant chemotherapy. METHODS: The medical records of LA-NSCLC patients treated with trimodality therapy at our institution between June 1999 and May 2019 were reviewed. The association between several clinicopathological factors and overall survival (OS) was analyzed. RESULTS: A total of 168 patients were included in this study. Regarding the prognosis, the 5-year OS rate was 68.1%, and the 2-year recurrence-free survival rate was 66.1% in the entire population. In multivariate analysis, we identified that high postoperative NLR, not pretreatment or preoperative NLR, was one of the independent factors for unfavorable OS (NLR high vs NLR low; hazard ratio = 2.45, 95% confidence interval: 1.53-3.94, p < 0.001). In addition, among patients with high postoperative NLR, patients who received postoperative adjuvant chemotherapy showed significantly better 5-year OS compared with those who did not (p = 0.016). On the other hand, postoperative adjuvant chemotherapy had no impact on the prognosis in patients with low NLR (p = 0.19). CONCLUSIONS: Our results suggest that high postoperative NLR was not only an independent unfavorable prognostic factor in patients with LA-NSCLC who were treated with trimodality therapy, but also a promising indicator for postoperative treatment in this population.

Chronic Lung Injury After Trimodality Therapy for Locally Advanced Non-Small Cell Lung Cancer.

BACKGROUND: Trimodality therapy is a treatment option for patients with locally advanced non-small cell lung cancer (LA-NSCLC). Thoracic radiation has both early (radiation pneumonitis) and late (chronic lung injury [CLI]) adverse effects on the lung. While CLI is expected to result in various problems in long-term survivors, these manifestations have not been precisely investigated. METHODS: We enrolled 112 LA-NSCLC patients who had received induction chemoradiotherapy followed by surgery, and then undergone follow-up computed tomography (CT) every 6 months for greater than 1 year. All chest CT images were reviewed to evaluate any injury of the pulmonary parenchyma. RESULTS: CLI at 1 year after surgery and its progression were observed in 94 (84%) and 38 (34%) patients, respectively. Progressive lung fibrosis as the first manifestation of CLI progression was most frequent after right middle and lower lobectomy. Cavity formation was the subsequent manifestation after progressive lung fibrosis , and chronic infection was the final stage of CLI. The cumulative rate of chronic infection was 76.4% at 10 years in patients with cavity formation. Ten patients with chronic infection included 7 cases of pulmonary aspergillosis and 2 cases of cavity infections with methicillin-resistant Staphylococcus aureus or Stenotrophomonas maltophilia. Among them, 4 patients required surgical interventions including completion pneumonectomy or fenestration. CONCLUSIONS: CLI is a common incidence after trimodality therapy for LA-NSCLC. CLI frequently results in cavity formation, which is a precursor of highly refractory chronic infections requiring surgical intervention. Appropriate management needs to be established for CLI developing after trimodality therapy.

Visceral Adipose Mass and Radiation Pneumonitis After Concurrent Chemoradiotherapy in Patients With Non-small-cell Lung Cancer.

Aim: To investigate whether muscle and adipose mass are associated with radiation pneumonitis (RP) in patients with non-small cell lung cancer undergoing preoperative concurrent chemoradiotherapy. Patients and Methods: We calculated body mass index and determined skeletal muscle, psoas muscle, visceral adipose tissue (VAI), and subcutaneous adipose tissue indices, and visceral-to-subcutaneous adipose tissue area ratio for patients using computed tomography. We examined their relationship with grade 2 or more RP. Results: Among 94 patients, 28 experienced grade 2 or more RP. On multivariate analysis, only VAI was associated with grade 2 or more RP (all p=0.026). The 6-month incidence rates of grade 2 or more RP were 21.4% and 36.8% in patients with VAI <39 and ≥39 cm 2 /m 2 , respectively. Conclusion: High visceral adipose mass is associated with grade 2 or more RP in patients undergoing preoperative concurrent chemoradiotherapy. Measuring visceral adipose mass may help to predict RP occurrence. Further studies are needed to validate our findings.