Association of immune-related adverse events with durvalumab efficacy after chemoradiotherapy in patients with unresectable Stage III non-small cell lung cancer.

BACKGROUND: Immune-related adverse events (irAEs) have been found to predict PD-L1 inhibitor efficacy in metastatic NSCLC. However, the relation of irAEs to clinical outcome for nonmetastatic NSCLC has remained unknown. METHODS: In this multicenter prospective study of Stage III NSCLC treated with PACIFIC regimen, the relation of irAEs to PFS was evaluated by 8-week landmark analysis to minimise lead-time bias as well as by multivariable analysis adjusted for baseline factors. irAEs were categorised as mild or nonmild according to whether they were treated with systemic steroid. RESULTS: Median PFS was 16.0 months, not reached, and 9.7 months for patients without (85 cases) or with mild (21 cases) or nonmild (21 cases) irAEs, respectively. Multivariable analysis indicated that nonmild irAEs were associated with poor PFS, with HRs of 3.86 (95% CI, 1.31-11.38) compared with no irAEs and 11.58 (95% CI, 2.11-63.63) compared with mild irAEs. This pattern was consistent after irAE grade, the number of durvalumab doses and immune profiles (PD-L1 score, CD8+ tumour-infiltrating lymphocyte density, and tumour mutation burden) were taken into consideration. CONCLUSIONS: The development of mild irAEs might predict a better survival outcome, whereas immunosuppressive steroid-treated irAEs were associated with a worse outcome, regardless of baseline clinical and immune profiles.

Trimethylsilyldiazomethane Disassembly at a Three-Fold Symmetric Iron Site.

The reaction of equimolar trimethylsilyldiazomethyllithium (LiTMSD) with high spin (S = 2) PhB(AdIm)3FeCl (PhB(AdIm)3- = tris(3-adamantylimidazol-2-ylidene)phenylborate) affords the corresponding N-nitrilimido complex PhB(AdIm)3Fe-N═N═C(SiMe3). This complex can be converted to the thermodynamically more favorable C-isocyanoamido isomer PhB(AdIm)3Fe-C═N═N(SiMe3) by reaction with an additional equivalent of LiTMSD. While the iron(II) complexes are four-coordinate, the diazomethane is bound side-on in the iron(I) congener PhB(AdIm)3Fe(N,N'-κ2-N2C(H)Si(CH3)3). The latter complex adopts high spin (S = 3/2) ground state and features an unusually weak C-H bond. Photolysis of the iron(II) complexes induces N═N bond cleavage, with the iron(II) cyanide PhB(AdIm)3Fe-C≡N and iron(IV) nitride PhB(AdIm)3Fe≡N complexes being the major products of the reaction. The same products are obtained when the iron(I) complex is photolyzed or treated with a fluoride source. The trimethylsilyldiazomethane-derived ligand disassembly reactions are contrasted with those observed for related tris(carbene)amine complexes.

Antibody-drug conjugates in solid tumors; new strategy for cancer therapy.

Antibody-drug conjugates (ADCs) have emerged as a novel class of anticancer treatment. ADCs are composed of three parts: a monoclonal antibody, a linker and a payload. A monoclonal antibody binds to the specific antigen present at the cancer cells, allowing selective delivery of the cytotoxic agents to the tumor site. Several ADCs are approved by the US Food and Drug Administration for the treatment of hematologic cancers and solid tumors with clinically meaningful survival benefit. However, the development of ADCs faces a lot of challenges and there is a need to get better understanding of ADCs in order to improve patient outcomes. Here, we briefly discuss the structure and mechanism of ADCs, as well as the clinical data of current approved ADCs in solid tumors.

Laparoscopic polyglycolic acid spacer placement for locally recurrent rectal cancer.

Carbon ion radiotherapy (CIRT) has received attention for the treatment of locally recurrent rectal cancer. When the surrounding primary organs are close to the irradiation site, a spacer is required to ensure safe irradiation. This work describes a novel technique using a bioabsorbable polyglycolic acid spacer placed laparoscopically and presents a technical report with five case studies. The short-term surgical outcomes were as follows: mean operating time 235 min with blood loss of 38 mL. CIRT was planned, and the patients underwent irradiation within 2 months of surgery. No pelvic infections occurred, and all procedures were performed safely. Herein, were present a technical report with reference to a video of the surgical procedure.

2023 Japan Society of clinical oncology clinical practice guidelines update for antiemesis.

BACKGROUND: The Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis 2023 was extensively revised to reflect the latest advances in antineoplastic agents, antiemetics, and antineoplastic regimens. This update provides new evidence on the efficacy of antiemetic regimens. METHODS: Guided by the Minds Clinical Practice Guideline Development Manual of 2017, a rigorous approach was used to update the guidelines; a thorough literature search was conducted from January 1, 1990, to December 31, 2020. RESULTS: Comprehensive process resulted in the creation of 13 background questions (BQs), 12 clinical questions (CQs), and three future research questions (FQs). Moreover, the emetic risk classification was also updated. CONCLUSIONS: The primary goal of the present guidelines is to provide comprehensive information and facilitate informed decision-making, regarding antiemetic therapy, for both patients and healthcare providers.

Non-pharmacological treatments for anticipatory nausea and vomiting during chemotherapy: a systematic review and meta-analysis of the Clinical Practice Guidelines for Antiemesis 2023.

BACKGROUND: Anticipatory chemotherapy-induced nausea and vomiting (CINV) is a conditioned response influenced by the severity and duration of previous emetic responses to chemotherapy. We aimed to evaluate the efficacy of non-pharmacologic interventions for anticipatory CINV among patients with cancer. METHODS: We conducted a systematic search in databases, including PubMed, the Cochrane Library, CINAHL, and Ichushi-Web, from January 1, 1990, to December 31, 2020. Randomized controlled trials, non-randomized designs, observational studies, or case-control studies that utilized non-pharmacological therapies were included. The primary outcomes were anticipatory CINV, with an additional investigation into adverse events and the costs of therapies. The risk-of-bias for each study was assessed using the Cochrane risk-of-bias tool, and meta-analysis was performed using Revman 5.4 software. RESULTS: Of the 107 studies identified, six met the inclusion criteria. Three types of non-pharmacological treatments were identified: systematic desensitization (n = 2), hypnotherapy (n = 2), and yoga therapy (n = 2). Among them, systematic desensitization significantly improved anticipatory CINV as compared to that in the control group (nausea: risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.49-0.72, p < 0.00001; vomiting: RR = 0.54, 95% CI = 0.32-0.91, p = 0.02). However, heterogeneity in outcome measures precluded meta-analysis for hypnotherapy and yoga. Additionally, most selected studies had a high or unclear risk of bias, and adverse events were not consistently reported. CONCLUSIONS: Our findings suggest that systematic desensitization may effectively reduce anticipatory CINV. However, further research is warranted before implementation in clinical settings.

Glenoid Track Revisited.

The risk of Hill-Sachs lesion (HSL) to cause instability depends not only on the HSL but also on the glenoid size. Clinically, the only method to assess the risk of instability considering the dynamic interaction of both, the HSL together with the glenoid bone loss, is the glenoid track concept. Since it was introduced in a cadaveric study, its clinical efficacy and validity have been reported in the literature. Sometimes, the medial margin of the footprint (lateral margin of the glenoid track) is difficult to identify when a HSL is overriding the footprint. In such cases, we propose a method to draw an imaginary line connecting two landmarks. Although 3D-CT is the most accurate and widely used method to assess on/off-track lesions, our interest gradually is shifting towards MRI, which has no radiation concern. The current MR method is still under way. There are various risk factors influencing the recurrent instability after surgery. The glenoid track concept deals with only one of these factors, i.e., instability caused by bony lesions. Therefore, the following two issues are important: 1) how to assess the glenoid track precisely and 2) how to incorporate other risk factors into consideration. The former can be achieved by obtaining the custom-made glenoid track width using not the fixed value of 83%, but more individualized value obtained by measuring the active horizontal extension angle of the opposite shoulder in the sitting position. At the same time, the gray zone (peripheral-track lesion) needs to be clearly defined. The latter can be achieved by incorporating the risk factors other than the bony lesions. One example is the glenoid track instability management score (GTIMS), a combination of the glenoid track concept and the instability severity index (ISI) score. This new scoring system is expected to increase the predictive potential of the scoring system, and accordingly to enhance clinical decision making.

When and how much does the muscle strength recover after arthroscopic superior capsular reconstruction?

BACKGROUND: Recently, arthroscopic superior capsular reconstruction (SCR) has been performed for irreparable large to massive rotator cuff tears and excellent clinical results have been reported. Although the muscle strength is reported to recover, it has not yet been clarified when and how much it recovers. The purpose of this study was to determine the recovery pattern of muscle strength after SCR. METHODS: We retrospectively reviewed 35 patients (mean age, 65 years) who met the following inclusion criteria: (1) patients with large to massive irreparable tears of the rotator cuff including the supraspinatus and infraspinatus tendons; (2) those with severe muscle atrophy and fatty change; (3) those who underwent assessment of muscle quality and strength by magnetic resonance imaging and dynamometry at 6 months, 1 year, and 2 years; (4) those with a minimum follow-up period of 2 years; and (5) those without severe osteoarthritis. The isometric muscle strength of scaption (ie, scapular-plane elevation), internal rotation, and external rotation in adduction was measured twice for each motion by a dynamometer. RESULTS: Relative to the muscle strength on the uninvolved side, the involved side showed 61% ± 21% in scaption, 63% ± 20% in external rotation, and 103% ± 29% in internal rotation at 2 years after surgery. Whereas no significant differences were observed between the 1-year and 2-year follow-up assessments, a significant difference in muscle strength of scaption was found between 6 months and 1 year (P = .0174). Graft retear was seen in 5 cases (14%). There was a trend that the muscle strength of scaption and external rotation in the no-retear group was greater than that in the retear group despite no significant difference (P = .0717 and P = .0824, respectively). CONCLUSION: The recovery of the muscle strength after SCR was observed until 1 year after surgery, and the muscle strength of scaption and external rotation returned to 60% of that on the uninvolved side at 2 years.

Location and Size of the Reverse Hill-Sachs Lesion in Patients with Traumatic Posterior Shoulder Instability.

BACKGROUND: In patients with traumatic posterior shoulder instability, little is known about the precise location and size of the reverse Hill-Sachs lesion. METHODS: Forty-nine shoulders of 47 patients with traumatic posterior instability were included in this study based on the following inclusion criteria: 1) a primary or recurrent traumatic posterior shoulder dislocation, and 2) the initial event was caused by trauma. Patients were excluded if they had: 1) no history of trauma, 2) prior shoulder surgery, 3) no CT examination, or 4) seizure cases. Three-dimensional images of the humerus reconstructed from CT images were reviewed using an image analysis software. The location and size of the reverse Hill-Sachs lesion were measured and described on a clock face on the humeral head. RESULTS: The reverse Hill-Sachs lesion was observed in 25 of 49 shoulders (51%). The reverse Hill-Sachs lesions were located between 1:37 and 2:48. The depth of the reverse Hill-Sachs lesion (mean ± SD) was 5.8 ± 2.2 mm. The extent of the reverse Hill-Sachs lesion was 35° ± 12°. The average orientation of the reverse Hill-Sachs lesion, represented by an angle measured from the 12 o'clock position, was 64° ± 12° and pointing towards 2:09 on a clock face. Length and width of reverse Hill-Sachs lesions were 9.7 ± 4.7 mm, 11.1 ± 3.6 mm, respectively. CONCLUSION: The reverse Hill-Sachs lesion was a semicircular compression fracture located on the anteromedial aspect of the humeral head. Compared with shoulders with anterior shoulder instability, the humeral defect was smaller and located more inferiorly in shoulders with posterior instability.

Statistical shape models that predict native glenoid width based on glenoid height are inaccurate in their current form: a cross-sectional study.

BACKGROUND: The extent of measurement errors of statistical shape models that predict native glenoid width based on glenoid height to subsequently determine the amount of anterior glenoid bone loss is unclear. Therefore, the aim of this study was to (1) create a statistical shape model based on glenoid height and width measured on 3-dimensional computed tomography (3D-CT) and determine the accuracy through measurement errors and (2) determine measurement errors of existing 3D-CT statistical shape models. MATERIALS AND METHODS: A retrospective cross-sectional study included all consecutive patients who underwent CT imaging before undergoing primary surgical treatment of traumatic anterior shoulder dislocation between 2007 and 2022 at the Tohoku University Hospital and affiliated hospitals. Patients were included when instability was unilateral and CT scans of both the injured and contralateral uninjured shoulder were available. 3D segmentations were created and glenoid height and width of the injured and contralateral uninjured side (gold standard) were measured. Accuracy was determined through measurement errors, which were defined as a percentage error deviation from native glenoid width (contralateral uninjured glenoid), calculated as follows: measurement error = [(estimated glenoid width with a statistical shape model - native glenoid width) / native glenoid width] × 100%. A linear regression analysis was performed to create a statistical shape model based on glenoid height according to the formula: native glenoid width = a × glenoid height + b. RESULTS: The diagnosis and procedure codes identified 105 patients, of which 69 (66%) were eligible for inclusion. Glenoid height demonstrated a very strong correlation (r = 0.80) with native glenoid width. The linear regression formula based on this cohort was as follows: native glenoid width = 0.75 × glenoid height - 0.61, and it demonstrated an absolute average measurement error of 5% ± 4%. The formulas by Giles et al, Chen et al and Rayes et al demonstrated absolute average measurement errors of 10% ± 7%, 6% ± 5%, and 9% ± 6%, respectively. CONCLUSION: Statistical shape models that estimate native glenoid width based on glenoid height demonstrate unacceptable measurement errors, despite a high correlation. Therefore, great caution is advised when using these models to determine glenoid bone loss percentage. To minimize errors caused by morphologic differences, preference goes to methods that use the contralateral side as reference.

Brigatinib in Japanese patients with ALK-positive non-small-cell lung cancer: Final results of the phase 2 J-ALTA trial.

The phase 2, single-arm, multicenter, open-label J-ALTA study evaluated the efficacy and safety of brigatinib in Japanese patients with advanced ALK+ non-small-cell lung cancer (NSCLC). One expansion cohort of J-ALTA enrolled patients previously treated with ALK tyrosine kinase inhibitors (TKIs); the main cohort included patients with prior alectinib ± crizotinib. The second expansion cohort enrolled patients with TKI-naive ALK+ NSCLC. All patients received brigatinib 180 mg once daily (7-day lead-in at 90 mg daily). Among 47 patients in the main cohort, 5 (11%) remained on brigatinib at the study end (median follow-up: 23 months). In this cohort, the independent review committee (IRC)-assessed objective response rate (ORR) was 34% (95% CI, 21%-49%); median duration of response was 14.8 months (95% CI, 5.5-19.4); median IRC-assessed progression-free survival (PFS) was 7.3 months (95% CI, 3.7-12.9). Among 32 patients in the TKI-naive cohort, 25 (78%) remained on brigatinib (median follow-up: 22 months); 2-year IRC-assessed PFS was 73% (90% CI, 55%-85%); IRC-assessed ORR was 97% (95% CI, 84%-100%); the median duration of response was not reached (95% CI, 19.4-not reached); 2-year duration of response was 70%. Grade ≥3 adverse events occurred in 68% and 91% of TKI-pretreated and TKI-naive patients, respectively. Exploratory analyses of baseline circulating tumor DNA in ALK TKI-pretreated NSCLC showed associations between poor PFS and EML4-ALK fusion variant 3 and TP53. Brigatinib is an important treatment option for Japanese patients with ALK+ NSCLC, including patients previously treated with alectinib.

Pembrolizumab plus chemotherapy in Japanese patients with metastatic squamous non-small-cell lung cancer in KEYNOTE-407.

The global phase III KEYNOTE-407 (NCT02775435) trial showed that pembrolizumab plus chemotherapy prolonged overall and progression-free survival (OS/PFS) versus placebo plus chemotherapy in patients with metastatic squamous non-small-cell lung cancer (NSCLC). We present outcomes of patients from Japan enrolled in KEYNOTE-407. Patients were randomized 1:1 to receive pembrolizumab 200 mg or placebo with paclitaxel 200 mg/m2 every 3 weeks (Q3W) or nab-paclitaxel 100 mg/m2 (weekly) plus carboplatin area under the concentration-time curve of 6 mg/mL/min Q3W for four cycles, followed by pembrolizumab or placebo Q3W for a total of 35 cycles. Primary end-points were OS and PFS per RECIST version 1.1 by blinded independent central review. Fifty patients were randomized at Japanese sites (pembrolizumab plus chemotherapy, n = 22; placebo plus chemotherapy, n = 28). Median follow-up time at data cut-off (May 9, 2019) was 15.1 (range, 0.5-24.0) months. Median OS (95% confidence interval [CI]) was 17.3 (12.5-not reached) versus 11.0 (8.6-19.5) months in the pembrolizumab plus chemotherapy versus placebo plus chemotherapy group (hazard ratio [HR] 0.56; 95% CI, 0.27-1.15). Median PFS (95% CI) was 8.3 (6.1-13.0) versus 7.2 (3.9-8.8) months (HR 0.65; 95% CI, 0.35-1.23). Grade 3-5 adverse events (AEs) occurred in 86% and 75% of patients, respectively. There were three fatal AEs, two of which were treatment-related (one from each treatment group, pneumonitis and pulmonary hemorrhage). Efficacy and safety outcomes were consistent with the global study and support the use of pembrolizumab plus chemotherapy in Japanese patients with metastatic squamous NSCLC.

Safety and effectiveness of pembrolizumab monotherapy in Japanese patients with unresectable urothelial carcinoma: a nation-wide post-marketing surveillance.

BACKGROUND: This study was conducted to identify factors associated with the safety and effectiveness of pembrolizumab in Japanese patients with unresectable urothelial carcinoma and to confirm the real-world safety and effectiveness of pembrolizumab in Japanese patients. METHODS: This multicenter, observational, post-marketing surveillance was conducted over a 1-year observation period starting at pembrolizumab initiation (200-mg pembrolizumab every 3 weeks); data were collected from case report forms (3 months and 1 year). Safety measures included treatment-related adverse events and adverse events of special interest (AEOSI). Effectiveness assessments included tumor response, objective response rate (ORR), and disease control rate (DCR). RESULTS: Overall, 1293 patients were evaluated for safety and 1136 for effectiveness. At 12 months, the treatment-related adverse event incidence was 53.8% (n = 696) and that of AEOSI was 25.0% (n = 323). The most frequent AEOSI of any grade were endocrinological disorder (10.4%, n = 134), interstitial lung disease (ILD) (7.2%, n = 93), and hepatic function disorder (4.9%, n = 64). Multivariate analysis demonstrated that the risk of developing ILD was almost seven times greater (odds ratio 6.60) in patients with a comorbidity of ILD, and approximately twice as high in patients aged ≥ 65 years (odds ratio 2.24) and with smoking history (odds ratio 1.79). The ORR was 26.1% and the DCR was 50.7%. The ORR was 46.4% in patients with a Bellmunt risk score of 0 and decreased as the Bellmunt risk score increased. CONCLUSIONS: This post-marketing surveillance confirmed the safety and effectiveness of pembrolizumab in Japanese patients with unresectable urothelial carcinoma in the real-world setting.

Randomized, open-label phase II study of brigatinib and carboplatin plus pemetrexed and brigatinib alone for chemotherapy-naive patients with ALK-rearranged non-squamous non-small cell lung cancer: treatment rationale and protocol design of the B-DASH study (WJOG 14720 L).

BACKGROUND: The ALTA-1L study compared brigatinib with crizotinib in untreated ALK-rearranged non-small cell lung cancer (NSCLC) patients, demonstrating the efficacy of brigatinib. Although the median progression-free survival (PFS) of brigatinib group was 24.0 months, the one-year PFS rate was 70%. In the NEJ009 study, patients with EGFR mutations showed improved outcomes with gefitinib plus chemotherapy compared with gefitinib monotherapy. To evaluate the efficacy of the combination of brigatinib with chemotherapy for patients with ALK-rearranged NSCLC, we designed B-DASH study (WJOG 14720L). METHODS: B-DASH study is a multicenter, two-arm, phase II study. Eligible patients have untreated stage IIIB, stage IIIC, stage IV, or postoperative relapse ALK-rearranged nonsquamous NSCLC. Patients will be randomized in a 1:1 ratio to receive brigatinib (180 mg once daily with a 7-day lead-in period at 90 mg) monotherapy or carboplatin (area under the curve = 5 on day 1) plus pemetrexed (500 mg/m2 on day 1) and brigatinib in a 3-week cycle for up to four cycles, followed by pemetrexed and brigatinib as maintenance therapy. The target hazard ratio of 0.62 is set based on the NEJ009 study. With one-sided alpha = 0.20 and power = 0.8, the sample size for the B-DASH study was calculated to be 110, considering the possibility of patients dropping out. The primary endpoint is PFS. The key secondary endpoints are the overall response rate and overall survival. We will evaluate tumor-derived DNA from plasma specimens before treatment, 42 days after administering the study drug, and on the day of progressive disease. Recruitment began in November 2021 and is ongoing. DISCUSSION: The efficacy of combination therapy with tyrosine kinase inhibitors and cytotoxic chemotherapy was demonstrated in patients with EGFR mutations but remains unclear in patients with ALK-rearranged NSCLC. The B-DASH study is the only trial of brigatinib combined with chemotherapy in patients with untreated ALK-rearranged NSCLC. TRIAL REGISTRATION: jRCT identifier: jRCTs041210103.

Afatinib plus osimertinib in the treatment of osimertinib-resistant non-small cell lung carcinoma: a phase I clinical trial.

BACKGROUND: Conquering acquired resistance to osimertinib remains a major challenge in treating patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Thus, we aimed to determine the safety and efficacy of combination treatment with osimertinib and afatinib for patients with acquired resistance to osimertinib. METHODS: This open-label phase I study was a feasibility study of the combination of afatinib and osimertinib for patients with advanced EGFR-positive NSCLC who had progressive disease after receiving osimertinib. The primary endpoint was to determine the maximum tolerated dose (MTD). We enrolled patients who received afatinib at three different dose levels (level 1, 20 mg; level 2, 30 mg; level 3, 40 mg) combined with osimertinib at a standard dose of 80 mg once per day. RESULTS: Thirteen patients were enrolled in this study. The MTD was defined as 30 mg afatinib when combined with daily oral administration of osimertinib (80 mg). The most frequent adverse events were diarrhea (76.9%), anemia (76.9%), and rash (69.2%). Considering the toxicity profiles during all treatment periods, the recommended oral dose of afatinib was determined as 20 mg daily, with an osimertinib dose of 80 mg. For all evaluable patients (n = 12), the response rate was 7.7% and the disease-control rate was 46.2%. CONCLUSION: Combination therapy with osimertinib and afatinib was tolerable; however, the synergistic effect of afatinib with osimertinib may be limited in osimertinib-resistant patients. TRIAL REGISTRATION: Japan Registry of Clinical Trials ID: jRCTs051180008, registered date: 08/11/2018.

Current methods of preventing infectious disease and managing febrile neutropenia in childhood cancer patients: a nationwide survey in Japan.

BACKGROUND: Preventing infection and managing febrile neutropenia (FN) is mandatory for children with cancer undergoing chemotherapy. However, the current situation in Japan is unknown. METHODS: We conducted a nationwide web-based questionnaire survey in 153 institutions treating childhood cancer in Japan. We asked about the type prophylaxis used to prevent infectious disease and manage FN. If patients with childhood cancer were managed by both pediatricians and surgeons at the same institution, we asked both to reply. RESULTS: We received replies from 117 departments at 111 centers: of these, 108 were from pediatricians. Laminar air flow for neutropenic patients, and frequent hand sanitization with ethanol, were widespread. Twenty-eight percent and forty percent of departments performed active surveillance by taking cultures from patients and the environment, respectively, before initiation of chemotherapy. Forty-four percent of departments administered prophylactic intravenous antibiotics according to patient status. Many departments measured serum (1,3)-ß-D glucan, procalcitonin, and aspergillus galactomannan at the onset of FN. Twenty-eight percent of departments used carbapenem as empirical therapy for FN. Some departments used prophylactic granulocyte-colony stimulating factor for acute leukemia. Seventy-two percent of departments used prophylactic immunoglobulin for hypogammaglobinemia caused by chemotherapy. Palivizumab was administered widely for respiratory syncytial virus prophylaxis in immunocompromised infants. CONCLUSION: As a whole, intensive care for infectious prophylaxis or FN is applied in Japan; however, the methods vary among centers, and some are excessive or inadequate. Therefore, it is desirable to conduct clinical trials and establish adequate care protocols for infection in children with cancer in Japan.

Overall survival analysis of patients enrolled in a randomized phase III trial comparing gefitinib and erlotinib for previously treated advanced lung adenocarcinoma (WJOG5108LFS).

BACKGROUND: Since the overall survival (OS) of patients enrolled in the first clinical phase III trial (WJOG5108L) was not recorded owing to time constraints, the present study (WJOG5108LFS) with a longer follow-up (66.6 months) aimed to compare OS of those treated with erlotinib (ER) and gefitinib (GE) for lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutation. METHODS: Among 536 enrolled patients, 362 (67.5%) were EGFR mutation-positive, including 182 in the ER arm and 180 in the GE arm. Median survival time (MST) and progression-free survival (PFS) were calculated using Kaplan-Meier survival curves. OS and PFS were determined for patients with EGFR mutation. RESULTS: MSTs of ER (n = 182) and GE arms (n = 180) were 31.97 and 27.98 months, respectively (P = 0.3573, hazard ratio = 1.116). MSTs of exon 19 mutation patients in ER (n = 99) and GE arms (n = 89) were 37.49 and 28.91 months, respectively (P = 0.3791). MSTs of L858 mutation patients in ER (n = 82) and GE arms (n = 89) were 22.98 and 27.79 months, respectively (P = 0.7836). In patients with brain metastasis harboring mutation, response rates were 32.8% and 22.2% (P = 0.160), MSTs were 23.46 and 23.89 months (P = 0.7410), and PFS were 9.49 and 6.98 months (P = 0.1481) in the ER (n = 67) and GE arms (n = 72), respectively. CONCLUSIONS: No significant differences in OS were observed between the ER and GE arms in all patients with EGFR mutation and those with brain metastasis harboring EGFR mutation.

Retrospective study of an incisional hernia after laparoscopic colectomy for colorectal cancer.

PURPOSE: This study aimed to examine the incidence of incisional hernia (IH) in elective laparoscopic colorectal surgery (LC) using regulated computed tomography (CT) images at intervals every 6 months. METHODS: We retrospectively examined the diagnosis of IH in patients who underwent LC for colorectal cancer at Kansai Medical University Hospital from January 2014 to August 2018. The diagnosis of IH was defined as loss of continuity of the fascia in the axial CT images. RESULTS: 470 patients were included in the analysis. IH was diagnosed in 47 cases at 1 year after LC. The IH size was 7.8 cm2 [1.3-55.6]. In total, 38 patients with IH underwent CT examination 6 months after LC, and 37 were already diagnosed with IH. The IH size was 4.1 cm2 [0-58.9]. The IH size increased in 17 cases between 6 months and 1 year postoperatively, and in 1 case, a new IH occurred. 47%(18/38) of them continued to grow until 1 year after LC. A multivariate analysis was performed on the risk of IH occurrence. SSI was most significantly associated with IH occurrence (OR:5.28 [2.14-13.05], p = 0.0003). CONCLUSION: IH occurred in 10% and 7.9% at 1 year and 6 months after LC. By examining CT images taken for the postoperative surveillance of colorectal cancer, we were able to investigate the occurrence of IH in detail.

The quantification of muscle activities during arm elevation following reverse shoulder arthroplasty or superior capsular reconstruction for irreparable rotator cuff tears using positron emission tomography.

BACKGROUND: Reverse shoulder arthroplasty (RSA) and superior capsular reconstruction (SCR) are recognized as surgical options for an irreparable rotator cuff tear. However, the postoperative changes of the muscle activity patterns remain unclear. The purpose of this study was to investigate the quantified muscle activities on shoulder elevation in patients treated with RSA or SCR using fluorine-18-labelled fluorodeoxyglucose-positron emission tomography. METHODS: Asymptomatic shoulders that underwent RSA or SCR and those without a rotator cuff tear were analyzed as the RSA, SCR, and control groups. All subjects underwent shoulder elevation exercise, followed by a fluorine-18-labelled fluorodeoxyglucose-positron emission tomography examination. Using previously established methods to quantify the uptake of each muscle on positron emission tomography images, the standard uptake values (SUVs) for 16 portions of the deltoid, rotator cuff, and periscapular muscles were obtained to compare the muscle activity patterns among 3 groups. RESULTS: The deltoid muscle showed the most characteristic differences according to the surgeries. The mean SUVs of the anterior, middle, and posterior deltoid were 3.3, 3.7, and 1.5 for the RSA group; 2.7, 4.2, and 1.5 for the SCR group; and 1.3, 2.0, and 0.9 for the control group, respectively. In comparison to the control group, both the RSA and SCR groups showed significantly increased SUVs at all portions of the deltoid muscle. The RSA group showed similar SUVs for the anterior and middle deltoid, whereas the SCR and control groups showed greatest SUVs at the middle deltoid. In addition, the serratus anterior, levator scapulae, and upper portion of the trapezius in the RSA group showed greater SUVs than in the control group. CONCLUSION: The deltoid muscle showed increased activity in the RSA and SCR groups. The middle deltoid was mainly used in the SCR group, whereas the anterior and middle deltoid, as well as the upward rotator muscles of the scapula, were mainly used in the RSA group.

Postoperative graft integrity affects clinical outcomes after superior capsule reconstruction using fascia lata autograft in posterior-superior rotator cuff tears: a multicenter study.

BACKGROUND: Previous studies have postulated that graft thickness and graft healing may be important factors for optimizing clinical outcomes of superior capsule reconstruction (SCR) for patients with irreparable rotator cuff tears (RCTs). However, the relationship between postoperative graft integrity and clinical outcomes after SCR remains unclear. We aimed to assess the relationship between postoperative graft integrity, including graft thickness and size of graft tear, and clinical outcomes after SCR in patients with irreparable RCTs. METHODS: This retrospective multicenter study included 188 patients (86 women, 102 men; mean age, 69.2 years; range, 49-87 years) with irreparable RCTs who underwent arthroscopic SCR using fascia lata autografts. Using magnetic resonance imaging, the graft integrity was evaluated postoperatively at or after 1 year and was classified, according to Hasegawa's classification, into 4 categories: type I-II, intact graft of sufficient thickness; type III, thinned graft without discontinuity; type IV, presence of a minor discontinuity; and type V, presence of a major discontinuity. We compared (1) baseline characteristics, (2) visual analog scale (VAS) for pain, (3) American Shoulder and Elbow Surgeons (ASES) score, (4) active shoulder range of motion, and (5) acromiohumeral distance (AHD) among 4 groups based on postoperative graft integrity. RESULTS: Magnetic resonance imaging scans revealed 152 shoulders (80.9%) with type I-II graft, 13 (6.9%) with type III graft, 13 (6.9%) with type IV graft, and 10 (5.3%) with type V graft. VAS and ASES scores significantly improved after SCR in all graft types (P < .0001 to P = .02). However, shoulders with type V grafts had significantly inferior postoperative VAS and ASES scores compared to those with type I-II grafts (P = .001 and P < .0001, respectively). Shoulders without graft tears (types I-II and III) showed significant improvements in shoulder elevation and internal rotation after SCR (P < .0001 to P = .02). In contrast, shoulders with large graft tears (type V) showed no significant improvement in shoulder range of motion. Postoperative acromiohumeral distance significantly increased only in shoulders with type I-II grafts (P < .0001). CONCLUSION: Postoperative graft thickness and size of graft tear affected clinical and radiographic outcomes after SCR using a fascia lata autograft. Patients with large graft tears had significantly inferior postoperative clinical scores compared to those with intact grafts of sufficient thickness, although arthroscopic SCR provided pain relief even in patients with graft tears. Shoulders with intact grafts of sufficient thickness restored glenohumeral stability and showed better clinical outcomes than those with graft thinning or tears.