Factors associated with quality of life in patients receiving palliative radiotherapy for bone metastases: a secondary cross-sectional analysis of data from a prospective multicenter observational study.

OBJECTIVE: To identify factors significantly associated with quality of life (QOL) and determine if these associations are strong enough to predict certain aspects of QOL without measuring them. METHODS: We conducted an exploratory secondary analysis of baseline data of 224 patients (enrolled between December 2020 and March 2021) from a previously published prospective observational study on radiotherapy for bone metastases at 26 centres. Using univariable linear regression, we assessed the association between patient/treatment factors and QOL scale scores as measured by the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 15-Palliative (QLQ-C15-PAL) and the EORTC QOL Questionnaire Bone Metastases module (QLQ-BM22). RESULTS: Age and sex were not significantly associated with QOL. Worse performance status, higher pain scores, and opioid and single-fraction use were significantly associated with most QOL scales; these four factors were associated with worse global QOL, worse functioning status, and more severe symptoms. The coefficients of determination for most QOL scales were less than 0.2, indicating that most of the variability in QOL scores was not explained by any of the explanatory variables. CONCLUSION: Performance status, pain intensity, and opioid and single-fraction use were significantly associated with most QOL scales. However, the associations were not strong enough to estimate QOL. ADVANCES IN KNOWLEDGE: To date, the association between treatment factors and QOL in patients with bone metastases has not been fully studied. We identified the factors that were significantly associated with QOL and found that these associations were not strong enough to predict QOL.

Endoscopic debulking canalization for optic pathway glioma with obstructive hydrocephalus.

Optic pathway gliomas (OPGs) are benign tumors that can stop growing or even shrink. In recent years, surgical resection has not been considered the first-line treatment because of its high risk of complications. Chemotherapy is the mainstay of treatment for growing OPGs. Surgical treatment for OPGs with obstructive hydrocephalus is required. Ventriculoperitoneal shunting is effective for all types of hydrocephalus. However, long-term management is required, especially in pediatric cases, and there is a risk of shunt-related complications over a long lifespan. Debulking surgery for OPGs allows us to avoid shunt placement by creating a waterway and releasing the hydrocephalus. To reduce the surgical risk and invasiveness, we used an endoscopic canalization technique with a small-diameter cylinder. In this article, we present a case of endoscopic canalization of an obstructive hydrocephalus caused by OPGs in a 14-year-old female to illustrate our surgical technique.(Trial registration Registry name and number: Efficacy and safety of the neuro-endoscopic treatment for brain tumors (2019-0254)).

Clinical results of proton beam radiotherapy for inoperable stage III non-small cell lung cancer: a Japanese national registry study.

This study presents the first data of a Japanese nationwide multi-institutional cohort and compares them with the findings of systematic literature reviews on radiation therapies and inoperable stage III non-small cell lung cancer (NSCLC) conducted by the Lung Cancer Working Group in the Particle Beam Therapy (PBT) Committee and Subcommittee at Japanese Society for Radiation Oncology. The Lung Cancer Working Group extracted eight reports and compared their data with those of the PBT registry from May 2016 to June 2018. All the analyzed 75 patients aged ≤80 years underwent proton therapy (PT) with concurrent chemotherapy for inoperable stage III NSCLC. The median follow-up period of the surviving patients was 39.5 (range, 1.6-55.6) months. The 2- and 3-year overall survival (OS) and progression-free survival rates were 73.6%/64.7% and 28.9%/25.1%, respectively. During the follow-up period, six patients (8.0%) had adverse events of Grade ≥ 3, excluding abnormal laboratory values. These included esophagitis in four patients, dermatitis in one and pneumonitis in one. Adverse events of Grade ≥ 4 were not observed. The results of these PBT registry data in patients with inoperable stage III NSCLC suggest that the OS rate was at least equivalent to that of radiation therapy using X-rays and that the incidence of severe radiation pneumonitis was low. PT may be an effective treatment to reduce toxicities of healthy tissues, including the lungs and heart, in patients with inoperable stage III NSCLC.

Income and Employment of Patients at the Start of and During Follow-up After Palliative Radiation Therapy for Bone Metastasis.

Purpose: The aim of this study was to understand the income and employment status of patients at the start of and during follow-up after palliative radiation therapy for bone metastasis. Methods and Materials: From December 2020 to March 2021, a prospective multi-institutional observational study was conducted to investigate income and employment of patients at the start of administration of radiation therapy for bone metastasis and at 2 and 6 months after treatment. Of 333 patients referred to radiation therapy for bone metastasis, 101 were not registered, mainly because of their poor general condition, and another 8 were excluded from the follow-up analysis owing to ineligibility. Results: In 224 patients analyzed, 108 had retired for reasons unrelated to cancer, 43 had retired for reasons related to cancer, 31 were taking leave, and 2 had lost their jobs at the time of registration. The number of patients who were in the working group was 40 (30 with no change in income and 10 with decreased income) at registration, 35 at 2 months, and 24 at 6 months. Younger patients (P = 0), patients with better performance status (P = 0), patients who were ambulatory (P = .008), and patients with lower scores on a numerical rating scale of pain (P = 0) were significantly more likely to be in the working group at registration. There were 9 patients who experienced improvements in their working status or income at least once in the follow-up after radiation therapy. Conclusions: The majority of patients with bone metastasis were not working at the start of or after radiation therapy, but the number of patients who were working was not negligible. Radiation oncologists should be aware of the working status of patients and provide appropriate support for each patient. The benefit of radiation therapy to support patients continuing their work and returning to work should be investigated further in prospective studies.

Subcutaneous transplantation of human embryonic stem cells-derived pituitary organoids.

Introduction: The pituitary gland, regulating various hormones, is central in the endocrine system. As spontaneous recovery from hypopituitarism is rare, and exogenous-hormone substitution is clumsy, pituitary replacement via regenerative medicine, using pluripotent stem cells, is desirable. We have developed a differentiation method that in mice yields pituitary organoids (POs) derived from human embryonic stem cells (hESC). Efficacy of these POs, transplanted subcutaneously into hypopituitary mice, in reversing hypopituitarism was studied. Methods: hESC-derived POs were transplanted into inguinal subcutaneous white adipose tissue (ISWAT) and beneath dorsal skin, a relatively avascular region (AR), of hypophysectomized severe combined immunodeficient (SCID) mice. Pituitary function was evaluated thereafter for ¾ 6mo, assaying basal plasma ACTH and ACTH response to corticotropin-releasing hormone (CRH) stimulation. Histopathologic examination of organoids 150d after transplantation assessed engraftment. Some mice received an inhibitor of vascular endothelial growth factor (VEGF) to permit assessment of how angiogenesis contributed to subcutaneous engraftment. Results: During follow-up, both basal and CRH-stimulated plasma ACTH levels were significantly higher in the ISWAT group (p < 0.001 - 0.05 and 0.001 - 0.005, respectively) than in a sham-operated group. ACTH secretion also was higher in the ISWAT group than in the AR group. Histopathologic study found ACTH-producing human pituitary-cell clusters in both groups of allografts, which had acquired a microvasculature. POs qPCR showed expression of angiogenetic factors. Plasma ACTH levels decreased with VEGF-inhibitor administration. Conclusions: Subcutaneous transplantation of hESC-derived POs into hypopituitary SCID mice efficaciously renders recipients ACTH-sufficient.

Incidence and Treatment Outcome of Radiation Pneumonitis in Patients With Limited-stage Small Cell Lung Cancer Treated With Concurrent Accelerated Hyperfractionated Radiation Therapy and Chemotherapy.

Purpose: This study aimed to clarify the characteristics of and evaluate the risk factors for radiation pneumonitis (RP) induced by chemoradiation therapy (CRT) using accelerated hyperfractionated (AHF) radiation therapy (RT) in patients with limited-stage small cell lung cancer (LS-SCLC). Methods and Materials: Between September 2002 and February 2018, 125 patients with LS-SCLC were treated with early concurrent CRT using AHF-RT. Chemotherapy was comprised of carboplatin/cisplatin with etoposide. RT was administered twice daily (45 Gy/30 fractions). We collected data regarding onset and treatment outcomes for RP, and analyzed the relationship between RP and total lung dose-volume histogram findings. Uni- and multivariate analyses were performed to assess patient- and treatment-related factors for grade ≥2 RP. Results: The median age of patients was 65 years, and 73.6% of participants were men. In addition, 20% and 80.0% of participants presented with disease stage II and III, respectively. The median follow-up time was 73.1 months. Grades 1, 2, and 3 RP were observed in 69, 17, and 12 patients, respectively. Grades 4 to 5 RP were not observed. RP was treated with corticosteroids in patients with grade ≥2 RP, without recurrence. The median time from initiation of RT to onset of RP was 147 days. Three patients developed RP within 59 days, 6 within 60 to 89 days, 16 within 90 to 119 days, 29 within 120 to 149 days, 24 within 150 to 179 days, and 20 within ≥180 days. Among the dose-volume histogram parameters, the percentage of lung volume receiving >30 Gy (V30) was most strongly related to the incidence of grade ≥2 RP, and the optimal threshold to predict RP incidence was V30 ≥20%. On multivariate analysis, V30 ≥20% was an independent risk factor for grade ≥2 RP. Conclusions: The incidence of grade ≥2 RP correlated strongly with a V30 of ≥20%. Contrarily, the onset of RP induced by concurrent CRT using AHF-RT may occur later. RP is manageable in patients with LS-SCLC.

Incidence of and risk factors for non-hematologic toxicity with combined radiotherapy and CDK4/6 inhibitors in metastatic breast cancer using dose-volume parameters analysis: a multicenter cohort study.

BACKGROUND: There is a lack of data on combined radiotherapy (RT) and cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) risk factors and toxicity. This study aimed to assess the incidence of and risk factors for non-hematologic toxicities in patients treated with combined RT and CDK4/6i using dose-volume parameter analysis. METHODS: We conducted a retrospective multicenter cohort study of patients with metastatic breast cancer receiving RT within 14 days of CDK4/6i use. The endpoint was non-hematologic toxicities. Patient characteristics and RT treatment planning data were compared between the moderate or higher toxicities (≥ grade 2) group and the non-moderate toxicities group. RESULTS: Sixty patients were included in the study. CDK4/6i was provided at a median daily dose of 125 mg and 200 mg for palbociclib and abemaciclib, respectively. In patients who received concurrent RT and CDK4/6i (N = 29), the median concurrent prescribed duration of CDK4/6i was 14 days. The median delivered RT dose was 30 Gy and 10 fractions. The rate of grade 2 and 3 non-hematologic toxicities was 30% and 2%, respectively. There was no difference in toxicity between concurrent and sequential use of CDK4/6i. The moderate pneumonitis group had a larger lung V20 equivalent dose of 2 Gy per fraction and planning target volume than the non-moderate pneumonitis group. CONCLUSIONS: Moderate toxicities are frequent with combined RT and CDK4/6i. Caution is necessary concerning the combined RT and CDK4/6i. Particularly, reducing the dose to normal organs is necessary for combined RT and CDK4/6i.

The importance of preserving the superior hypophyseal artery infundibular branch in craniopharyngioma surgery.

PURPOSE: Postoperative pituitary dysfunction, a critical problem in the treatment of craniopharyngiomas, can occur even when the pituitary stalk is preserved. We hypothesized that compromise of the primary superior hypophyseal artery (pSHA) might be related to this occurrence. METHODS: We performed a retrospective review of 131 patients with craniopharyngioma who underwent surgery from April 2009 to September 2021. The inclusion criteria were initial surgery, endoscopic transsphenoidal surgery, preoperative normal pituitary function or pituitary dysfunction in one axis, and morphological preservation of the pituitary stalk. The branches of the pSHA consist mainly of the chiasmatic branches (Cb), infundibular branches (Ib), and descending branches (Db). We analyzed the association between postoperative pituitary function and preservation of these branches. RESULTS: Twenty patients met the criteria. Preoperative anterior pituitary function was normal in 18 patients, and there was isolated growth hormone deficiency in two patients. No patient had preoperative diabetes insipidus (DI). Anterior pituitary function was unchanged postoperatively in eight patients. Of these eight patients, bilateral preservation of pSHA Ib was confirmed in seven patients. Bilateral preservation of pSHA Ib was the only factor associated with preserved anterior pituitary function (p < 0.01). Fifteen patients were free of permanent DI, and the preservation of any given pSHA branch produced no significant difference in the postoperative occurrence of permanent DI. CONCLUSIONS: Our study shows that bilateral preservation of pSHA Ib provides favorable postoperative anterior pituitary function in craniopharyngioma surgery; however, such preservation may have little effect on the postoperative occurrence of DI.

Clinical impact of tumour burden on the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy in non-small-cell lung cancer.

BACKGROUND: Programmed cell death 1 (PD-1)/programmed cell death ligand (PD-L1) inhibitors plus chemotherapy (ICI + Chemo) is the standard treatment for advanced non-small-cell lung cancer (NSCLC). However, the impact of tumour burden on the efficacy of ICI + Chemo remains unknown. METHODS: We retrospectively evaluated 92 patients with advanced NSCLC treated with ICI + Chemo. Tumour burden was assessed as the sum of the longest diameter of the target lesion (BSLD) and number of metastatic lesions (BNMLs). We categorised the patients into three groups based on the combined BSLD and BNML values. RESULTS: Sixty-eight patients (74%) had progressive disease or died. Forty-four patients (48%) in the low-BSLD group had a median progression-free survival (PFS) of 9.5 months, whereas patients in the high-BSLD group had a median PFS of 4.6 months (hazard ratio [HR] = 0.54, p = 0012). Twenty-five patients (27%) in the low-BNML group had a median PFS of 9.6 months, whereas patients in the high-BNML group had a median PFS of 6.5 months (HR = 0.51, p = 0.029). Low-BSLD and low-BNML were associated independently with improved PFS in multivariate analysis. Analysis of the tumour burden combined with BSLD and BNML revealed a trend towards improved PFS as the tumour burden decreased, with median PFS of 22.3, 8.7, and 3.9 months in the low- (N = 13), medium- (N = 42) and high-burden (N = 37) groups respectively. CONCLUSIONS: Our findings demonstrated that a high tumour burden negatively impacts the efficacy of ICI + Chemo in patients with advanced NSCLC.

Osteosclerotic change as a therapeutic response to gefitinib in symptomatic non-small cell lung cancer bone metastasis.

BACKGROUND: Despite improvement in the overall survival of patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation, the effects of EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment on bone metastasis remain unclear. This study investigated radiological responses to gefitinib regarding bone metastasis in patients. METHODS: We treated 260 patients with NSCLC and symptomatic bone metastasis. Thirty-seven patients harboring EGFR mutation were treated with gefitinib for more than 30 days and followed up for more than 3 months (GEF group). We performed a retrospective observational study by selecting 36 cases without EGFR-TKI treatment, at least 3 months of follow-up, and at least two radiological evaluations as the control group. We assessed the best overall radiological response, interval from treatment initiation to appearance of a radiological response, and the local response maintenance rate. RESULTS: The best effect in the GEF group was 98% partial response or better, which was significantly higher than the 57% observed in the control group (p < 0.001). The GEF and control groups maintained 83% and 42% local response maintenance rates at one year, respectively (p < 0.001). In the GEF with radiotherapy group, the local response maintenance rate was maintained at 92% at 1 year, while in the GEF without RT group, there was a decrease in the local response maintenance rate from 270 days. CONCLUSION: Gefitinib treatment for bone metastases in patients harboring EGFR mutation resulted in a beneficial osteosclerotic change in most patients. Combined gefitinib and radiotherapy provide long-lasting local control of bone metastases.

Feasibility of linac-based fractionated stereotactic radiotherapy and stereotactic radiosurgery for patients with up to ten brain metastases.

BACKGROUND: Linac-based fractionated stereotactic radiotherapy (fSRT) and stereotactic radiosurgery (SRS) are increasingly being used to manage patients with multiple metastases. This retrospective cohort study aimed to compare the outcomes after linac-based fSRT and SRS between three patient groups classified based on the number of brain metastases (BMs): 1 BM, 2-4 BM, 5-10 BM. METHODS: The data of consecutive patients with 1-10 BMs treated with fSRT or SRS between July 2016 and June 2018 at a single institution were collected. Patients with previous whole-brain radiotherapy (WBRT), concurrent use of WBRT, or surgical resection were excluded from the analysis. A total of 176 patients were classified into three groups according to the number of BMs: 78, 67, and 31 patients in 1 BM, 2-4 BM, and 5-10 BM, respectively. The Kaplan-Meier method was used to estimate overall survival (OS) curves, and the cumulative incidence with competing risks was used to estimate local control (LC), distant intracranial failure (DIF), and radiation necrosis (RN). RESULTS: Median OS was 19.8 months (95% confidence interval [CI] 10.2-27.5), 7.3 months (4.9-11.1), and 5.1 months (4.0-9.0) in 1 BM, 2-4 BM, and 5-10 BM, respectively. Compared to 2-4 BM, 1 BM had significantly better OS (hazard ratio [HR] 0.59, 95% CI 0.40-0.87; p = 0.0075); however, 5-10 BM had comparable OS (HR 1.36, 95% CI 0.85-2.19; p = 0.199). There was no significant difference in LC, DIF, and RN between tumor number groups, but DIF was lower in 1 BM. RN of grade 2 or higher occurred in 21 patients (13.5%); grade 4 and 5 RN were not observed. CONCLUSIONS: The linac-based fSRT and SRS for patients with 5-10 BMs is comparable to that for patients with 2-4 BMs in OS, LC, DIF, and RN. It seems reasonable to use linac-based fSRT and SRS in patients with 5-10 BMs.

Endoscopic Trans-Mini-Cylinder Biopsy for Intraparenchymal Brain Lesions.

OBJECTIVE: The biopsy procedure is intended to obtain an adequate specimen volume from the targeted area while ensuring minimal damage to the normal brain. We performed navigation-guided endoscopic biopsy using a small-diameter cylinder to reduce the invasiveness of the biopsy procedure and ensure a sufficient amount of tissue is collected. We examined whether it is possible to reduce brain tissue injury by using a small-diameter cylinder and improve safety and effectiveness by using an endoscope to directly observe the lesion and achieve hemostasis. METHODS: Patients who underwent endoscopic biopsy surgery using a 6-mm-diameter cylinder for intraparenchymal lesions were enrolled in this study. Postoperative hematoma formation and the extent of trajectory scarring were assessed. RESULTS: Fifty-two procedures performed on 51 patients were analyzed in this study. Postoperative neurological deterioration was not observed in any patient. A pathological diagnosis was made for all patients. Postoperative computed tomography revealed no hematoma after 49 procedures and a small hematoma after 3 procedures, and no patients required additional treatment. A postoperative trajectory scar less than 5 mm in diameter was observed after 30 procedures, a scar of 5-10 mm was observed after 19 procedures, a scar larger than 10 mm was observed after 3 procedures at 1 week after surgery, and 40, 6 and 0 scars were observed at 3 months after surgery. CONCLUSIONS: Endoscopic biopsy using a small-diameter cylinder is a possible alternative biopsy technique for intraparenchymal lesions. This surgical technique is useful, especially in patients at risk of hemorrhagic complications.

Immunological and Genetic Characterization of Patients With Head and Neck Cancer who Developed Recurrence.

BACKGROUND/AIM: The recurrence rate of head and neck squamous cell carcinoma (HNSCC) remains high; thus the control of recurrence is a clinical problem to be challenged. To clarify the precise mechanism, specific immunological biomarkers responsible for recurrence were investigated. PATIENTS AND METHODS: The expression levels of immune response-associated and Shizuoka Cancer Center 820 cancer-associated genes, and genetic mutations from whole-exome sequencing were compared between HNSCC patients who developed recurrence (n=8) and HNSCC patients who did not develop recurrence (n=19) using a volcano plot analysis. Cytokine and epithelial-mesenchymal transition marker genes were analyzed using quantitative PCR. Tumor-infiltrating lymphocytes, immune checkpoint molecules, and human papilloma virus status were investigated using immunohistochemistry (IHC). RESULTS: Twenty-seven evaluable patients with HNSCCs received radiation therapy after surgery. Recurrence was identified in 8 patients. TP53 mutations tended to be higher in patients who developed recurrence than in those who did not develop recurrence (75% vs. 31.6%). Gene expression profiling showed the down-regulation of T cell activation genes (ICOS, CD69 and CD83) and the upregulation of the ERBB4, EGFR, VEGF, HIF1A, TGFB1, TWIST1, IL-8, and PAX7 genes, which suggested the activation of the TP53 mutation-TGF-ß1-PAX7 pathway and epithelial-mesenchymal transition. Additionally, IHC indicated a tendency toward a reduction in T cell accumulation and an increase in M2-type macrophage infiltration in tumors that recurred. CONCLUSION: A TP53 mutation-mediated immune-suppressive state in the tumor microenvironment and TGF-ß1-PAX7-mediated EMT might contribute to the promotion of recurrence in patients with HNSCC after postoperative radiotherapy.

Predicting the efficacy of first-line immunotherapy by combining cancer cachexia and tumor burden in advanced non-small cell lung cancer.

BACKGROUND: Cancer cachexia and tumor burden predict efficacies of programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and chemotherapy or pembrolizumab in non-small cell lung cancer (NSCLC). There are no predictive models that simultaneously assess cancer cachexia and tumor burden. METHODS: In the present retrospective study, we reviewed the medical records of patients with advanced NSCLC who received cancer immunotherapy as first-line systemic therapy. Clinical immune predictive scores were defined according to multivariate analysis of progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 157 patients were included in the present study (75 treated with PD-1/PD-L1 inhibitors + chemotherapy; 82, pembrolizumab monotherapy). Multivariate analysis for PFS revealed that PD-L1 tumor proportion scores <50%, a total target lesion diameter ≥76 mm, and cancer cachexia were independently associated with poor PFS. Multivariate analysis for OS revealed that ≥4 metastases and cancer cachexia were significantly associated with poor OS. In the immune predictive model, the median PFS was 21.7 months in the low-risk group (N = 41); 7.6 in the medium-risk group (N = 64); and 3.0 in the high-risk group (N = 47). The median OS were not reached, 22.4 and 9.1 months respectively. Our immune predictive model was significantly associated with PFS (p < 0.001) and OS (p < 0.001). CONCLUSION: We proposed the immune predictive model, including tumor burden and cancer cachexia, which may predict the efficacy and survival outcome of first-line immunotherapy in advanced NSCLC.

Efficacy and safety of the endoscopic "wet-field" technique for removal of supratentorial cavernous malformations.

OBJECTIVE: Cerebral cavernous malformations (CMs) presenting with focal neurological symptoms or mass effects require surgical removal. In recent years, cylindrical retractors have been widely utilized for the removal of deep-seated lesions during both microscopic and endoscopic surgery. In the present study, we evaluated the efficacy and safety of endoscopic transcylinder removal of CMs using a novel wet-field technique. METHODS: We included 13 patients with supratentorial CMs who had undergone endoscopic transcylinder surgery between April 2013 and March 2022. One patient experienced recurrence of the CM and underwent a second endoscopic transcylinder surgery. Therefore, we retrospectively evaluated 14 procedures. The surgical field was continuously irrigated with artificial cerebrospinal fluid to maintain expansion and visualization of the tumor bed. We termed this method as the "wet-field technique." Patient characteristics, symptoms, and pre- and postoperative magnetic resonance imaging results were obtained from medical records. RESULTS: The average maximum CM diameter was 35.3 mm (range: 10-65 mm). Cylinder diameters were 6 mm in eight procedures, 10 mm in four procedures, and 17 mm in one procedure. Wet-field technique was applied in all cases. The endoscope provided a bright field of view even under water. Continuous water irrigation made it easier to observe the entire tumor bed which naturally expanded by water pressure. Gross total resection was achieved in 13 procedures, while subtotal resection was achieved in one procedure. No surgical complications were observed. CONCLUSIONS: The endoscopic transcylinder removal using wet-field technique is safe and effective for the removal of symptomatic intracranial supratentorial CMs.

Multi-institutional feasibility study of intensity-modulated radiotherapy with chemotherapy for locally advanced non-small cell lung cancer.

BACKGROUND: This multi-institutional clinical trial evaluated the feasibility of intensity-modulated radiotherapy (IMRT) for patients with locally advanced non-small cell lung cancer (NSCLC). METHODS: The major inclusion criteria were clinical stage III NSCLC, age 20-74 years, and Eastern Cooperative Oncology Group performance status 0-1. Patients were treated with either cisplatin + S-1 (CS; four cycles every 4 weeks) or carboplatin + paclitaxel (CP; administered weekly with thoracic radiotherapy [RT], plus two consolidation cycles) concurrently with IMRT (60 Gy in 30 fractions). The primary endpoint was a treatment completion rate, defined as at least two cycles of CS or five cycles of CP during IMRT and completing 60 Gy IMRT within 56 days after the start of treatment, assumed its 90% confidence interval exceeds 60%. RT quality assurance was mandatory for all the patients. RESULTS: Twenty-two patients were registered. One patient withdrew due to pulmonary infection before starting treatment. RT plans were reviewed and none was judged as a protocol violation. Grade 2 and 3 pneumonitis occurred in four (19%) and one (5%) patients, respectively. Seventeen patients met the primary endpoint, with a treatment completion rate of 77.3% (90% confidence interval [CI] 58.0%-90.6%). Four patients failed to complete chemotherapy due to chemotherapy-related adverse events, but 20 patients completed IMRT. There were no treatment-related deaths. The 2-year progression-free and overall survival rates were 31.8% (95% CI 17.3%-58.7%) and 77.3% (95% CI 61.6%-96.9%), respectively. CONCLUSION: The treatment completion rate did not meet the primary endpoint, but 20 of 22 patients completed IMRT.

Modified Shoelace Dural Closure with Collagen Matrix in Extended Transsphenoidal Surgery.

Extended endonasal transsphenoidal surgery (eTSS) offers a wide surgical field for various parasellar lesions; however, intraoperative high-flow cerebrospinal fluid (CSF) leakage is inevitable. Therefore, secure sellar reconstruction methods are essential to prevent postoperative CSF leakage. Although collagen matrix has been applied for dural reconstruction in neurosurgery, its suitability for application in extended eTSS remains unclear. Eighteen patients underwent modified shoelace dural closure using collagen matrix after lesionectomy via extended eTSS. In this technique, a collagen matrix, which was placed subdurally (inlay graft), was continuously sutured with both open dural edges like a shoelace. Then, another collagen matrix was placed epidurally (onlay graft), and rigid reconstruction was performed using the septal bone and a resorbable fixation mesh. Postoperative CSF leakage did not occur in 17 patients but did occur in 1 patient with tuberculum sellae meningioma. In this case, the CSF leakage point was detected just around the area between the coagulated dura and the adjacent collagen matrix. The collagen matrix harvested from this area was pathologically examined; neovascularization and fibroblastic infiltration into the collagen matrix were not detected. On the other hand, neovascularization and fibroblast infiltration into the collagen matrix were apparent on the surface of the collagen matrix harvested from the non-CSF leakage area. Our novel dural closure technique using collagen matrix could be an effective option for sellar reconstruction in extended eTSS; however, it should be applied in patients in whom normal dural edges are preserved.

Deciphering the clinical features of heterogeneous stage III non-small cell lung cancer in Japanese real-world clinical practice: Expanded cohort of the SOLUTION study.

OBJECTIVES: To evaluate the actual treatment patterns with respective outcomes and the patient characteristics of stage III non-small cell lung cancer (NSCLC) in Japan. MATERIALS AND METHODS: Patients (aged ≥20 years at diagnosis) who were diagnosed with stage III NSCLC between January 2013 and December 2014 and underwent surgery, chemoradiotherapy (CRT), chemotherapy (CT), or radiotherapy (RT) at 11 institutions in Japan were consecutively registered in this retrospective, observational study (SOLUTION; UMIN000031385). Study measures included patient characteristics, first-line treatments, overall survival (OS), progression-free survival, objective response rate, and incidence of radiation-related adverse events. RESULTS: The study population comprised 744 patients. The tumors were classified as stage IIIA and IIIB in 58.9% and 41.1% of patients, respectively. The tumors were considered resectable at diagnosis in 25.0% of patients. First-line treatments were surgery (20.0%), CRT (46.1%), CT (22.2%), and RT (11.7%). The median OS (mOS) in the overall population was 25.4 months and the 3-year OS rate was 38.7%. Among the four first-line treatment cohorts, OS most favored the surgery cohort: mOS was 43.4 months and the 3-year OS rate was 53.8%. Prognostic factors for OS in each treatment modality were analyzed using multivariable analysis and included the following: age, performance status, and histological type for the surgery cohort; sex, histological type, and primary lesion location (lower lobe) for the CRT cohort; and performance status and clinical stage for the RT cohort. The timing of peak incidence of pneumonitis from the start of first-line treatment was 18-20 and 12-14 weeks in the CRT and RT cohorts, respectively. CONCLUSION: Patients with clinical stage III NSCLC received a variety of treatments selected to the clinical background and tumor status, and we clarified the outcome and prognostic factors. These findings will be a useful reference for future studies evaluating newly introduced treatments for stage III NSCLC.

Prognostic impact of pneumonitis after durvalumab therapy in patients with locally advanced non-small cell lung cancer.

BACKGROUND: Prognostic data on Japanese patients receiving durvalumab after chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (LA-NSCLC) are insufficient. Whether pneumonitis has prognostic implications in patients with LA-NSCLC who have received durvalumab also remains unclear. METHODS: We retrospectively assessed the data of 82 consecutive patients who had received durvalumab after CRT at our institution between May 2018 and August 2020. A multi-state model was used to establish the associations between co-variables and progression-free survival (PFS). RESULTS: The median observation period for all the censored cases was 14.5 months (5.7-28.9 months), the median PFS was 22.7 months, and the 12-month PFS rate was 62.3% (95% CI: 50.2%-72.3%). The median percentage of the lung volume receiving a radiation dose in excess of 20 Gray (V20) was 22% (4%-35%). Thirteen patients (16%) had Grade 1 pneumonitis before receiving durvalumab, and 62 patients developed pneumonitis after durvalumab (Grades 1, 2, and 3 in 25 [30%], 32 [39%], and 4 [5%], respectively). Twenty-four patients (29%) completed the 1-year durvalumab treatment period, 16 patients (20%) were continuing to receive treatment, and 42 (51%) had discontinued treatment. In a multi-state analysis, patients with pneumonitis before durvalumab therapy had a poorer PFS than those without pneumonitis (HR: 4.29, p = 0.002). The development of Grade 2 or higher pneumonitis after durvalumab was not a significant prognostic factor for PFS (HR: 0.71, p = 0.852). CONCLUSION: Grade 2 or higher pneumonitis after durvalumab was not a prognostic factor of PFS in LA-NSCLC patients received durvalumab.