Interim PET-guided ABVD or ABVD/escalated BEACOPP for newly diagnosed advanced-stage classic Hodgkin lymphoma (JCOG1305).

This single-arm confirmatory study (JCOG1305) aimed to evaluate the utility of interim positron emission tomography (iPET)-guided therapy for newly diagnosed advanced-stage classic Hodgkin lymphoma (cHL). Patients aged 16-60 years with cHL received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and then underwent an iPET scan (PET2), which was centrally reviewed using a five-point Deauville scale. PET2-negative patients continued an additional four cycles of ABVD, whereas PET2-positive patients switched to six cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP). The co-primary endpoints were 2-year progression-free survival (PFS) among all eligible and PET2-positive patients. Ninety-three patients were enrolled between January 2016 and December 2019. One patient was ineligible because of a diagnostic error. The median age of the 92 eligible patients was 35 (interquartile range, 28-48) years. Forty (43%) patients had stage III disease, and 43 (47%) had stage IV disease. The remaining nine (10%) patients had stage IIB disease with risk factors. Nineteen PET2-positive (21%) patients received eBEACOPP, 18 completed six cycles of eBEACOPP, 73 PET2-negative (79%) patients continued ABVD, and 70 completed an additional four cycles of ABVD. With a median follow-up period of 41.1 months, the 2-year PFS of 92 eligible patients and 19 PET2-positive patients were 84.8% (80% confidence interval [CI], 79.2-88.9) and 84.2% (80% CI, 69.7-92.1), respectively. Both primary endpoints were met at the prespecified threshold. This study demonstrates that iPET-guided therapy is a useful treatment option for younger patients with newly diagnosed advanced-stage cHL. Registration number: jRCTs031180218.

Vaginal involvement as a rare extranodal manifestation in advanced-stage follicular lymphoma: a case report and literature review.

Apart from bone marrow involvement, extranodal involvement of follicular lymphoma (FL) is rare. Gynecologic FL is seldom reported, among which the vagina is the rarest involved site. No vaginal involvement in advanced-staged FL was reported before. Here, we report a case of FL with systemic involvement including the vagina.

Delphi consensus recommendations on treatment for advanced-stage marginal zone lymphoma in South Korea.

Due to the lack of treatment guidelines for the management of advanced-stage marginal zone lymphoma (MZL), only one chemoimmunotherapy-cyclophosphamide, vincristine, and prednisone plus rituximab (R-CVP)-is reimbursed in the first-line setting in South Korea. The aim of this study was to develop a consensus-based recommendation for the treatment of patients with advanced-stage MZL. Twelve hematologist oncologists participated in a two-round Delphi process to identify consensus on the management of patients with advanced-stage MZL in South Korea. Physicians rated their level of agreement with each statement on a four-point Likert scale. Statements were divided into two sections: definitions used in clinical practice and clinical management of patients with advanced-stage MZL. Consensus was reached for 23 of 33 (69.7%) and 5 of 13 statements (38.5%) in rounds 1 and 2, respectively. There was strong consensus (91.7%) that advanced-stage MZL subtypes are defined according to the Lugano staging system. First-line systemic treatment should be prescribed for patients with symptomatic advanced-stage MZL. Although there was unanimous agreement that R-CVP is the standard first-line treatment for advanced-stage MZL, physicians also agreed that bendamustine with rituximab (BR) has greater efficacy than R-CVP as first-line treatment (91.7%). For the treatment of relapsed/refractory advanced-stage MZL, BR and R-CVP can be repeated in patients with short (< 24 months) and long remission periods (≥ 24 months), respectively. This study provides insights on the management of patients with advanced-stage MZL in South Korea. This may enhance clinical decision-making, thus improving patient outcomes.

Clinical features, prognostic stratification, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma: a multi-institutional real-world study.

The present study aimed to investigate the clinical features, prognosis, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma (ENKTCL). This real-world study retrospectively reviewed 56 newly diagnosed advanced-stage non-nasal type ENKTCL patients from two large-scale Chinese cancer centers in the last 10-15 years and screened 139 newly diagnosed advanced-stage nasal type ENKTCLs admitted during the same period for comparison. The non-nasal type ENKTCLs exhibited significantly higher Ki-67 expression levels compared to nasal type disease (P = 0.011). With a median follow-up duration of 75.03 months, the non-nasal group showed slightly inferior survival outcomes without statistically significant differences compared to the nasal group (median overall survival (OS): 14.57 vs. 21.53 months, 5-year OS: 28.0% vs. 38.5%, P = 0.120). Eastern Cooperative Oncology Group (ECOG) score ≥ 2 (hazard ratio (HR) = 2.18, P = 0.039) and lactic dehydrogenase (LDH) elevation (HR = 2.44, P = 0.012) were significantly correlated with worse OS in the non-nasal group. First-line gemcitabine-based chemotherapy regimens showed a trend toward slightly improved efficacy and survival outcomes compared to non-gemcitabine-based ones in the present cohort of non-nasal ENKTCLs (objective response rate: 91.7% vs. 63.6%, P = 0.144; complete response rate: 50.0% vs. 33.3%, P = 0.502; median progression-free survival: 10.43 vs. 3.40 months, P = 0.106; median OS: 25.13 vs. 9.30 months, P = 0.125), which requires further validation in larger sample size studies. Advanced-stage non-nasal type patients could achieve comparable prognosis with nasal cases after rational therapy. The modified nomogram-revised index (including age, ECOG score, and LDH) and modified international prognostic index (including age, ECOG score, LDH, and number of extranodal involvement) functioned effectively for prognostic stratification in non-nasal type ENKTCLs.

Prognostic value of HE4 in advanced-stage, high-grade serous ovarian cancer: Analysis of HE4 kinetics during NACT, predicting surgical outcome and recurrence in comparison to CA125.

OBJECTIVES: To assess the prognostic value of human epididymis protein 4 (HE4) kinetics during and after neoadjuvant chemotherapy (NACT) cycles compared with cancer antigen 125 (CA-125), in predicting the surgical outcomes of interval debulking surgery (IDS) in patients with advanced-stage, high-grade serous ovarian cancer. METHODS: This retrospective cohort study was conducted at Severance Hospital in Seoul, South Korea and involved 123 women with high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who were diagnosed between April 2015 and July 2020. Three outcomes were considered: the chemotherapy response score (CRS) by omentum, residual disease after IDS, and recurrence. Other clinical, imaging, and biological parameters at baseline, during NACT cycles, and pre- and postoperative time were collected and analyzed. RESULTS: We observed a substantial and gradual decrease in both CA-125 level (median from 1612 to 85.55 U/mL; p < 0.001) and HE4 level (514.7 to 87.7 pmol/L; p < 0.001) during NACT cycles, while pre-to-postoperative reduction was only significant for HE4 (median from 77.3 to 62.0 pmol/L (p < 0.001)). Of the total patients, 4.1% showed no response to NACT (chemoresistance) and 65.9% had a partial response. Residual disease was observed in 55 (44.7%) patients. Recurrence occurred in 90 patients (73.2%), with a median progression-free survival of 15.28 months. The percent reduction in CA-125 level- but not HE4 - during NACT was significantly associated with CRS (by omentum); the reduction in CA-125 during NACT cycles was higher when the CRS was found to be 3 and 2 (median = 96.4 [IQR = 8.3] and 93.7 [12.2] respectively) compared to score 1 (68.3 [34.1]), and the difference was statistically significant (p = 0.004). However, no significant association was observed between the percent reduction in CA-125 or HE4 levels during NACT and residual disease or recurrence. The normalization of HE4 - but not CA-125 - before surgery was predictive for surgery outcome; that is, an abnormal preop HE4 level was associated with a residual disease risk ratio of 2.72 (95% CI = 1.27-5.79). CONCLUSION: Monitoring HE4 or CA-125 levels has low prognostic value in patients with advanced-stage, high-grade serous ovarian cancer who are treated with NACT followed by IDS. However, the preoperative level of the HE4 biomarker may be useful in identifying patients at higher risk for suboptimal cytoreductive surgery or who may require more extensive surgery. Further prospective studies are warranted to explore the prognostic utility of eventual combinations of clinical, radiological, and biological parameters, notably by using artificial intelligence-based models.

Effect of surgical volume on short-term outcomes of cytoreductive surgery for advanced-stage ovarian cancer: A population-based study from the Dutch Gynecological Oncology Audit.

OBJECTIVE: Despite lacking clinical data, the Dutch government is considering increasing the minimum annual surgical volume per center from twenty to fifty cytoreductive surgeries (CRS) for advanced-stage ovarian cancer (OC). This study aims to evaluate whether this increase is warranted. METHODS: This population-based study included all CRS for FIGO-stage IIB-IVB OC registered in eighteen Dutch hospitals between 2019 and 2022. Short-term outcomes included result of CRS, length of stay, severe complications, 30-day mortality, time to adjuvant chemotherapy, and textbook outcome. Patients were stratified by annual volume: low-volume (nine hospitals, <25), medium-volume (four hospitals, 29-37), and high-volume (five hospitals, 54-84). Descriptive statistics and multilevel logistic regressions were used to assess the (case-mix adjusted) associations of surgical volume and outcomes. RESULTS: A total of 1646 interval CRS (iCRS) and 789 primary CRS (pCRS) were included. No associations were found between surgical volume and different outcomes in the iCRS cohort. In the pCRS cohort, high-volume was associated with increased complete CRS rates (aOR 1.9, 95%-CI 1.2-3.1, p = 0.010). Furthermore, high-volume was associated with increased severe complication rates (aOR 2.3, 1.1-4.6, 95%-CI 1.3-4.2, p = 0.022) and prolonged length of stay (aOR 2.3, 95%-CI 1.3-4.2, p = 0.005). 30-day mortality, time to adjuvant chemotherapy, and textbook outcome were not associated with surgical volume in the pCRS cohort. Subgroup analyses (FIGO-stage IIIC-IVB) showed similar results. Various case-mix factors significantly impacted outcomes, warranting case-mix adjustment. CONCLUSIONS: Our analyses do not support further centralization of iCRS for advanced-stage OC. High-volume was associated with higher complete pCRS, suggesting either a more accurate selection in these hospitals or a more aggressive approach. The higher completeness rates were at the expense of higher severe complications and prolonged admissions.

Advanced-stage breast cancer diagnosis and its determinants in Ethiopia: a systematic review and meta-analysis.

INTRODUCTION: Worldwide, breast cancer is the primary cause of illness and death. Unless early detected and treated breast cancer is a life-threatening tumor. Advanced-stage presentation is greatly linked with short survival time and increased mortality rates. In Ethiopia nationally summarized evidence on the level of advanced-stage breast cancer diagnosis is scarce. Therefore, this systematic review and meta-analysis aimed to determine the pooled prevalence of advanced-stage breast cancer diagnosis and its determinants in Ethiopia. METHOD: By following PRISMA guidelines, a systematic review and meta-analysis were carried out. To include relevant publications, a broad literature search was conducted in the African Online Journal, PubMed, Google Scholar, and Embase which are published until last search date; June 15, 2023. To prevent further duplication this review was registered in PROSPERO database with ID no of CRD42023435096. To determine the pooled prevalence, a weighted inverse variance random effect model was applied. I2 statistics and the Cochrane Q-test were computed to determine heterogeneity. To evaluate publication bias, a funnel plot, and Egger's regression test were used. RESULT: A total of 924 articles were sought and finally 20 articles were included in this review. The pooled prevalence of advanced-stage breast cancer diagnosis in Ethiopia was 72.56% (95%CI; 68.46-76.65%). Use of traditional medicine as first choice (AOR = 1.32, 95% CI: (1.13-1.55)), delay of > 3 months in seeking care (AOR = 1.24, 95% CI: (1.09-1.41)), diagnosis or health system delay of > 2 months (AOR = 1.27, 95% CI: (1.11-1.46)), rural residence (AOR = 2.04, 95% CI: (1.42 - 2.92)), and chief complaint of a painless breast lump (AOR = 2.67, 95% CI: (1.76-4.06)) were significantly associated to advanced-stage diagnosis. CONCLUSION: In Ethiopia, more than two-thirds of breast cancer cases are diagnosed at an advanced stage. Use of traditional medicine before diagnostic confirmation, delay in seeking care, health system delay, rural residence, and chief complaint of painless breast lump were positively associated with an advanced-stage diagnosis. Policymakers and program designers give great focus to those delays so as to seek and access modern diagnosis and treatment as early as possible specifically focusing on those who are rurally residing.

Robot-Assisted Vaginal Natural Orifice Transluminal Endoscopic Surgery (RvNOTES) With Total Hysterectomy for Management of Stage IV Endometriosis With/Without Complete Cul-de-Sac Obliteration: 23-Case Pilot Feasibility Study.

STUDY OBJECTIVE: To show feasibility and short-term outcomes of robot-assisted vaginal NOTES (RvNOTES) for the treatment of stage IV endometriosis during total hysterectomy with/without complete cul-de-sac obliteration. DESIGN: Retrospective case series. SETTING: Single academic tertiary care hospital in Houston, Texas, USA. PATIENTS: Twenty-three adult women with stage IV endometriosis. INTERVENTIONS: RvNOTES with total hysterectomy for excision of severe endometriosis. MEASUREMENTS AND MAIN RESULTS: Patients were assessed for various metrics including total operative time, robot dock time, robot console time, hysterectomy time, estimated blood loss, perioperative pain using the Visual Analogue Scale (VAS), and complications. The mean total operative time was 224.3 minutes. The study also found that patients with complete cul-de-sac obliteration had significantly longer operative times and higher estimated blood loss compared to those with partial or no obliteration. Postoperative VAS pain scores showed a significant reduction over a 6-week period. Complications included one case of complete ureteral transection, pelvic hematoma with infection, vaginal abscess, urinary tract infection, and pneumonia. CONCLUSION: Our findings suggest that RvNOTES may be a feasible surgical approach in expert hands for treating stage IV endometriosis, even in cases with complete obliteration of the cul-de-sac.

The role of central neck dissection and adjuvant treatment in pT4aN0 laryngeal carcinoma treated with open partial horizontal laryngectomy.

PURPOSE: The study aimed to identify parameters that could predict oncological and functional outcomes in patients with pT4aN0 laryngeal squamous cell carcinoma (LSCC) who underwent open partial horizontal laryngectomy (OPHL). The role of paratracheal neck dissection (PTND) was analyzed as the primary outcome. Additionally, the study compared the outcomes of patients who underwent postoperative radio/chemotherapy (PORT/PORCT) with those who refused or did not adhere to adjuvant treatments. METHODS: Twenty-nine OPHL patients whose pathological exam was consistent with pT4aN0-x disease were enrolled and their clinical charts were retrospectively reviewed. The study analyzed oncological outcomes, such as local, regional, and distant recurrence rates (RR), overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS). Additionally, functional results were analyzed, including decannulation rate, hospitalization time, and postoperative complication rate. RESULTS: The study revealed and overall recurrence rate of 27%. The final rates for OS and DSS were 68% and 79%, respectively. Based on the univariate analysis the PTND was significantly associated with longer DFS. No significant differences inoncological outcomes were observed between pT4a patients who underwent adjuvant radio/radiochemotherapy and those who did not, in terms of RR, DFS, DSS or OS. However, adjuvant treatment was found to significantly increase decannulation time. CONCLUSIONS: In a properly super-selected subgroup of patients with pT4aN0 LSCC, OPHL may beconsidered as a conservative surgical option even without adjuvant treatment. However, for optimal oncological outcomes, it is strongly recommended to consider a central compartment dissection in cases of hypoglottic and anterior extra-laryngeal tumor extension.

The effects of illness perception on death anxiety and satisfaction with life in patients with advanced gastrointestinal cancer.

OBJECTIVES: This study was conducted to determine the effects of illness perception on death anxiety and satisfaction with life in patients with advanced gastrointestinal cancer. METHODS: This cross-sectional and correlational study was conducted with 125 patients with cancer who were admitted to the oncology clinic of a university hospital in the Central Anatolian Region of Turkey between March and December 2022 and who met the research criteria and accepted to participate in the study. The data were collected with "Patient descriptive information form," "Brief Illness Perception Questionnaire (BIPQ)," "Scale of Death Anxiety (SDA)," and "Satisfaction with Life Scale (SWLS)." RESULTS: It was found that mean BIPQ score of the patients was 39.54 ± 12.82, the mean SDA score was 8.02 ± 3.16, and the mean SWLS score was 14.74 ± 5.19. BIPQ total score was found to affect SDA total score positively (ß = .751) and SWLS total score negatively (ß = - .591). SDA total score was found to affect SWLS total score negatively (ß = -.216) (p < .05). SIGNIFICANCE OF RESULTS: It was found that patients with advanced gastrointestinal cancer had moderate level of illness perception and life satisfaction, and high death anxiety. It was found that as illness perception of the patients increased, their death anxiety increased and satisfaction with life decreased. In addition, it was found that as the death anxiety of patients increased, their satisfaction with life decreased.

Intensive therapy can improve long-term survival in newly diagnosed, advanced-stage extranodal NK/T-cell lymphoma: A multi-institutional, real-world study.

The study investigated the treatment and prognosis of advanced-stage extranodal natural killer/T-cell lymphoma (ENKTL). With a median follow-up of 75.03 months, the median overall survival (mOS) for the 195 newly diagnosed stage III/IV ENKTL patients was 19.43 months, and estimated 1-, 2-, 3- and 5-year OS were 59.5%, 46.3%, 41.8% and 35.1%, respectively. Chemotherapy (CT) + radiotherapy (RT) compared to CT alone (P = .007), and hematopoietic stem cell transplantation (HSCT) compared to non-HSCT (P < .001), both improved OS. For patients ≤60 years and ineligible for HSCT, other therapies with complete remission led to comparable OS (P = .141). Nine patients ever treated with chidamide achieved a median progression-free survival (mPFS) and mOS of 53.63 (range, 3.47-92.33) and 54.80 (range, 5.50-95.70) months, and four with chidamide maintenance therapy (MT) achieved a mPFS and mOS of 55.83 (range, 53.27-92.33) and 60.65 (range, 53.70-95.70) months, possibly providing an alternative option for non-HSCT patients. Non-anthracycline (ANT)- compared to ANT-, asparaginase (Aspa)- compared to non-Aspa- and gemcitabine (Gem)- compared to non-Gem-based regimens, prolonged PFS (P = .031; P = .005; P = .009) and OS (P = .010; P = .086; P = .003), respectively. Multivariate analysis demonstrated that Gem-based regimens improved PFS (HR = 0.691, P = .061) and OS (HR = 0.624, P = .037). Gem + Aspa combinations slightly improved PFS and OS compared to regimens containing Gem or Aspa alone (P > 0.05). First-line "intensive therapy," including CT (particularly Gem + Aspa regimens), RT, HSCT and alternative chidamide MT, was proposed and could improve long-term survival for advanced-stage ENKTLs. Ongoing prospective clinical studies may shed further light on the value of chidamide MT.

Staging lymph nodes and blood at diagnosis in mycosis fungoides identifies patients at increased risk of progression to advanced stage: A retrospective cohort study.

BACKGROUND: Risk factors for progression to advanced-stage mycosis fungoides (MF) are poorly defined. METHODS: The authors performed a single-center, retrospective cohort study among patients with MF at an academic medical center from 1990 to 2020 to identify clinical variables associated with progression to advanced-stage MF (stage IIB-IVB), and 388 patients who had a clinicopathologic diagnosis of early stage (IA-IIA) MF were identified from their cutaneous lymphoma database. Baseline clinical characteristics, laboratory values, imaging, and blood flow cytometry or T-cell receptor gene rearrangement (TCR) data were collected. Logistic regression was used to assess risk factors associated with progression. RESULTS: Overall, 93 of 388 patients (24.0%) progressed to advanced stage. Patients who progressed had an increased risk of death (hazard ratio, 4.50; 95% CI, 2.89-7.00; p < .001). Progression was associated with a higher overall stage at diagnosis, tumor stage, lymph node stage, low-level blood involvement, as measured with TCR data and/or flow cytometry, and elevated lactate dehydrogenase (LDH). Limitations included missing data for LDH, imaging, peripheral blood TCR data, or flow cytometry assessed at diagnosis. CONCLUSIONS: Staging and baseline laboratory assessments with imaging, peripheral blood flow cytometry, TCR data, and LDH in patients who have newly diagnosed MF may identify those who are at risk for progression to advanced stage.

First-line single-agent pembrolizumab for PD-L1-positive (tumor proportion score ≥ 50%) advanced non-small cell lung cancer in the real world: impact in brain metastasis: a national French multicentric cohort (ESCKEYP GFPC study).

BACKGROUND: Few real-world data are available in patients with advanced metastatic non-small cell lung cancer (NSCLC) treated with first-line immunotherapy, particularly in those with brain metastases at treatment initiation. METHODS: This was a national, retrospective, multicenter study that consecutively included all patients with PD-L1-positive (tumor proportion score ≥ 50%) advanced NSCLC who initiated first-line treatment with pembrolizumab as a single agent between May 2017 (date of availability of pembrolizumab in this indication in France) to November 22, 2019 (approval of the pembrolizumab-chemotherapy combination). Data were collected from medical records with local response assessment. RESULTS: The cohort included 845 patients and 176 (20.8%) had brain metastases at diagnosis. There were no significant differences in outcomes for patients with and without brain metastases: 9.2 (95% CI 5.6-15) and 8 (95% CI 6.7-9.2, p = 0.3) months for median progression-free survival (PFS) and, 29.5 (95% CI 17.2-NA) and 22 (95% CI 17.8-27.1, p = 0.3) months for median overall survival (OS), respectively. Overall response rates were 47% and 45% in patients with and without cerebral metastases. In multivariate analysis, performance status 2-4 vs. 0-1 and neutrophil-to-lymphocyte ratio ≥ 4 vs. < 4 were the main independent negative factors for OS; brain metastasis was not an independent factor for OS. CONCLUSION: In this large multicenter cohort, nearly 20% of patients initiating pembrolizumab therapy for advanced NSCLC had cerebral metastases. There was no significant difference in response rates, PFS and OS between patients with and without brain metastases.

Protocol of the RACB study: a multicenter, single-arm, prospective study to evaluate the efficacy of resection of initially unresectable hepatocellular carcinoma with atezolizumab combined with bevacizumab.

BACKGROUND: Although the standard therapy for advanced-stage hepatocellular carcinoma (HCC) is systemic chemotherapy, the combination of atezolizumab and bevacizumab (atezo + bev) with a high objective response rate may lead to conversion to resection in patients with initially unresectable HCC. This study aims to evaluate the efficacy of atezo + bev in achieving conversion surgery and prolonged progression-free survival (PFS) for initially unresectable HCC. METHODS: The RACB study is a prospective, single-arm, multicenter, phase II trial evaluating the efficacy of combination therapy with atezo + bev for conversion surgery in patients with technically and/or oncologically unresectable HCC. The main eligibility criteria are as follows: (1) unresectable HCC without a history of systemic chemotherapy, (2) at least one target lesion based on RECIST ver. 1.1, and (3) a Child‒Pugh score of 5-6. The definition of unresectable tumors in this study includes macroscopic vascular invasion and/or extrahepatic metastasis and massive distribution of intrahepatic tumors. Patients will be treated with atezolizumab (1200 mg/body weight) and bevacizumab (15 mg/kg) every 3 weeks. If the patient is considered resectable on radiological assessment 12 weeks after initial chemotherapy, the patient will be treated with atezolizumab monotherapy 3 weeks after combination chemotherapy followed by surgery 3 weeks after atezolizumab monotherapy. If the patient is considered unresectable, the patient will continue with atezo + bev and undergo a radiological assessment every 9 weeks until resectable or until disease progression. The primary endpoint is PFS, and the secondary endpoints are the overall response rate, overall survival, resection rate, curative resection rate, on-protocol resection rate, and ICG retention rate at 15 min after atezo + bev therapy. The assessments of safety and quality of life during the treatment course will also be evaluated. The number of patients has been set at 50 based on the threshold and the expected PFS rate at 6 months after enrollment of 40% and 60%, respectively, with a one-sided alpha error of 0.05 and power of 0.80. The enrollment and follow-up periods will be 2 and 1.5 years, respectively. DISCUSSION: This study will elucidate the efficacy of conversion surgery with atezo + bev for initially unresectable HCC. In addition, the conversion rate, safety and quality of life during the treatment course will also be demonstrated. TRIAL REGISTRATION: This study is registered in the Japan Registry of Clinical Trials (jRCTs051210148, January 7, 2022).

Protocol for the 2ND-STEP study, Japan Clinical Oncology Group study JCOG1802: a randomized phase II trial of second-line treatment for advanced soft tissue sarcoma comparing trabectedin, eribulin and pazopanib.

BACKGROUND: Soft tissue sarcomas (STS) are a rare type of malignancy comprising a variety of histological diagnoses. Chemotherapy constitutes the standard treatment for advanced STS. Doxorubicin-based regimens, which include the administration of doxorubicin alone or in combination with ifosfamide or dacarbazine, are widely accepted as first-line chemotherapy for advanced STS. Trabectedin, eribulin, pazopanib, and gemcitabine plus docetaxel (GD), which is the empirical standard therapy in Japan, are major candidates for second-line chemotherapy for advanced STS, although clear evidence of the superiority of any one regimen is lacking. The Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group (JCOG) conducts this trial to select the most promising regimen among trabectedin, eribulin, and pazopanib for comparison with GD as the test arm regimen in a future phase III trial of second-line treatment for patients with advanced STS. METHODS: The JCOG1802 study is a multicenter, selection design, randomized phase II trial comparing trabectedin (1.2 mg/m2 intravenously, every 3 weeks), eribulin (1.4 mg/m2 intravenously, days 1 and 8, every 3 weeks), and pazopanib (800 mg orally, every day) in patients with unresectable or metastatic STS refractory to doxorubicin-based first-line chemotherapy. The principal eligibility criteria are patients aged 16 years or above; unresectable and/or metastatic STS; exacerbation within 6 months prior to registration; histopathological diagnosis of STS other than Ewing sarcoma, embryonal/alveolar rhabdomyosarcoma, well-differentiated liposarcoma and myxoid liposarcoma; prior doxorubicin-based chemotherapy for STS, and Eastern Cooperative Oncology Group performance status 0 to 2. The primary endpoint is progression-free survival, and the secondary endpoints include overall survival, disease-control rate, response rate, and adverse events. The total planned sample size to correctly select the most promising regimen with a probability of > 80% is 120. Thirty-seven institutions in Japan will participate at the start of this trial. DISCUSSION: This is the first randomized trial to evaluate trabectedin, eribulin, and pazopanib as second-line therapies for advanced STS. We endeavor to perform a subsequent phase III trial comparing the best regimen selected by this study (JCOG1802) with GD. TRIAL REGISTRATION: This study was registered with the Japan Registry of Clinical Trials ( jRCTs031190152 ) on December 5, 2019.

Predictive value on advance hodgkin lymphoma treatment outcome of end-of treatment FDG PET/CT in the HD0607 clinical trial.

The Lugano classification for response assessment in lymphoma recommends the use of the 5-point-scale Deauville Score (DS) to assess response evaluation of end-of-treatment FDG-PET/CT (eotPET) in Hodgkin Lymphoma (HL); nevertheless, there is a paucity of data on its accuracy and reproducibility. We focus here on the cohort of advanced stage IIb-IV HL patients enrolled in the HD0607 clinical trial (NCT identifier 00795613) that having had a negative interim PET performed 6 cycles of ABVD (Doxorubicin, Vinblastine, Vincristine and Dacarbazine) and then performed an eotPET. Negative patients were randomized to radiotherapy and no further treatment while positive patients were treated based on local policies. eotPET was re-evaluated independently by two readers evaluated and progression free survival was analysed (PFS). eotPET of 254 patients were analysed. The median follow-up was 43 months. The best receiver operator characteristics cut-off values to distinguish positive and negative patients was 4. The area-under-the-curve was 0.81 (95%CI, 0.70-0.91). Three-years PFS was 0.95 (95% CI 0.90-0.97) in eotPET negative and 0.22 (95% CI 0.11-0.43) in eotPET positive. DS demonstrated a good reproducibility of positivity/negativity between the readers consensus and local site evaluation where the agreement occurred on 95.0% of patients. The present study demonstrates that eotPET is an accurate tool to predict treatment outcome in HL and confirms the appropriateness of the Lugano classification for eotPET evaluation.

Textbook outcome as a composite outcome measure to compare hospital performances regarding cytoreductive surgery for ovarian cancer: A nationwide population-based study.

OBJECTIVE: Textbook outcome (TO) is a composite outcome measure used in surgical oncology to compare hospital outcomes using multiple quality indicators. This study aimed to develop TO as an outcome measure to assess healthcare quality for patients undergoing cytoreductive surgery (CRS) for advanced-stage ovarian cancer. METHODS: This population-based study included all CRS for FIGO IIIC-IVB primary ovarian cancer registered in the Netherlands between 2017 and 2020. The primary outcome was TO, defined as a complete CRS, combined with the absence of 30-day mortality, severe complications, and prolonged length of admission (≥ten days). Delayed start of adjuvant chemotherapy (≥six weeks) was not included in TO because of missing data. Logistic regressions were used to assess the association of case-mix factors with TO. Hospital variation was displayed using funnel plots. RESULTS: A total of 1909 CRS were included, of which 1434 were interval CRS and 475 were primary CRS. TO was achieved in 54% of the interval CRS cohort and 47% of the primary CRS cohort. Macroscopic residual disease after CRS was the most important factor for not achieving TO. Age ≥ 70 was associated with lower TO rates in multivariable logistic regressions. TO rates ranged from 40% to 69% between hospitals in the interval CRS cohort and 22% to 100% in the primary CRS cohort. In both analyses, one hospital had significantly lower TO rates (different hospitals). Case-mix adjustment significantly affected TO rates in the primary CRS analysis. CONCLUSIONS: TO is a suitable composite outcome measure to detect hospital variation in healthcare quality for patients with advanced-stage ovarian cancer undergoing CRS. Case-mix adjustment improves the accuracy of the hospital comparison.

Toxicity and feasibility of vincristine, etoposide, and carboplatin alternating with vincristine, doxorubicin, and cyclophosphamide in children with advanced retinoblastoma in Guatemala.

Retinoblastoma is highly curable, with event-free survival (EFS) of greater than 95% in high-income countries. However, in lower middle-income countries, outcomes of EFS are 30%-60% due to delayed diagnosis and lack of resources resulting in extra-ocular disease. We report the toxicity profile and outcomes of intensified therapy for advanced retinoblastoma: vincristine, etoposide, carboplatin (VEC) alternating with vincristine, doxorubicin, and cyclophosphamide (VDoCx) in Guatemala. Compared to VEC alone, similar rates of neutropenia, anemia, and thrombocytopenia were seen, with no toxic deaths. Although survival was not a primary objective, a modest survival benefit supports further investigation of VEC+VDoCx for advanced retinoblastoma.

The effect of progestin therapy in advanced and recurrent endometrial cancer: A systematic review and meta-analysis.

BACKGROUND: Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades, but there is limited evidence on response prediction with biomarkers and toxicity. OBJECTIVES: To review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumour grade. SEARCH STRATEGY: We used the search terms 'Endometrial cancer', 'Progestins', 'Disease progression', 'Recurrence' and related terms in Pubmed, Embase and Cochrane databases. SELECTION CRITERIA: Studies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, with fewer than ten cases and with sarcoma histology were excluded. DATA COLLECTION AND ANALYSIS: Evaluation for bias was performed with the Revised Cochrane RoB2 tool for randomised studies and the ROBINS-I tool for non-randomised studies. A random effects meta-analysis was performed with the overall response rate (ORR), clinical benefit rate and toxicity as primary outcome measures. MAIN RESULTS: Twenty-six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95% CI 25-36), the clinical benefit rate was 52% (95% CI 42-61). In PR-positive EC, the ORR was 55%, compared with 12% in PR-negative disease (risk difference 43%, 95% CI 15-71). Severe toxicity occurred in 6.5%. CONCLUSIONS: Progestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR-positive disease. The role of PR expression in relation to progression-free survival and overall survival is unclear.

An association of epidermal growth factor receptor mutation subtypes with prognostic prediction and site-specific recurrence in advanced stage lung cancer patients.

BACKGROUND: Concerning the different clinical behavior of epidermal growth factor receptor (EGFR) subtypes in advanced-stage lung cancer patients, the current study aimed to evaluate the clinical, pathological, and prognostic significance of EGFR mutation subtypes, and treatment response in patients with advanced-stage lung cancer. METHODS AND RESULTS: A retrospective study enrolled a total of 346 patients with advanced-stage lung cancer tested for EGFR mutation. EGFR mutation was analyzed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Statistical analysis was performed using SPSS version 20.0. EGFR mutation was evident in 38% of patients with the highest prevalence of exon 19 deletions. A higher incidence of 19-deletions and 20-insertions were observed in young patients, while a higher incidence of L858R was noted in old age patients. Patients with de-novo T790M failed to improve their OS by any of the treatment modalities. Patients with de-novo T790M mutation have a higher risk of developing lung, liver, and multiple site metastases while patients with L858R mutation have a higher risk of developing brain metastasis. Additionally, patients with 19 deletion mutation did not improve their OS after receiving conventional chemotherapy hence, they demonstrate better survival only after EGFR-TKIs. Multivariate survival analysis predicted chemotherapy as an independent predictor of OS. CONCLUSION: Besides clinicopathological and prognostic consequences of EGFR mutation and mutation subtypes, patients harboring TKI sensitive, or insensitive mutations reveal different secondary disease development and hence should be treated accordingly for better survival. Current findings may provide the basis for a better treatment strategy.