Taste and Smell Functions in Long-term Survivors after Childhood Medulloblastoma/CNS-PNET

Purpose Our aim was to investigate taste and smell functions in survivors, with a minimum of 2 years follow-up time, after treatment of childhood medulloblastoma/CNS-PNET. Methods This cross-sectional study included 40 survivors treated ≤ 20 years of age. Taste strips with four concentrations of sweet, sour, salt, and bitter were used to assess taste function in all participants. Score from 0-16; ≥ 9 normogeusia, < 9 hypogeusia, and complete ageusia which equals no sensation. No sensation of a specific taste quality equals ageusia of that quality. Thirty-two participants conducted smell testing using three subtests of Sniffin’ sticks; threshold, discrimination, and identification. Together they yield a TDI-score from 1-48; functional anosmia ≤ 16.00, hyposmia >16.00 - < 30.75, normosmia ≥ 30.75 - < 41.50, and ≥ 41.50 super smeller. Results were compared with normative data. Survivors subjectively rated their taste and smell functions using a numerical rating scale (NRS) score 0-10. Results Forty survivors with a mean follow-up of 20.5 years, 13 (32.5 %) were diagnosed with hypogeusia, nine (22.5 %) of these being ageusic of one or more taste qualities. Seventeen (53 %) of 32 participants were diagnosed with hyposmia. Comparing survivors with hyposmia to those with normosmia, a significant difference (p<0.05) was found in TDI-score and in all the subtests. The mean NRS score of subjective ratings of functions were high.Conclusion Our study showed impaired taste and smell functions in long-term survivors of childhood MB/CNS-PNET using objective measurements. However, subjective ratings did not reflect objective findings.

Examination of The Characteristics of Long-Term Survivors Among Patients With Gallbladder Cancer With Liver Metastasis Who Underwent Surgical Treatment: A Retrospective Multicenter Study (ACRoS1406)

Background: Gallbladder cancer (GBC) with liver metastasis is considered unresectable. However, there have been infrequent reports of long-term survival in patients with GBC and liver metastases. Therefore, we examined the characteristics of long-term survivors of gallbladder cancer with liver metastasis.Methods: A retrospective multicenter study of 503 patients with GBC (mean age, 68.6 years; female, 52%) was performed. Although patients with pre-operatively diagnosed GBC and liver metastasis were generally excluded from resection, some cases identified during surgery were resected.Result: In patients with resected stage III/IV GBC (n = 228), the period 2007–2013 (vs. 2000–2006, hazard ratio 0.55), other type histology (vs. well/moderate histology, hazard ratio 2.34), ≥2 liver metastases (vs. one liver metastasis, hazard ratio 4.30), and positive margin resection (vs. complete resection with a negative margin, hazard ratio 1.57) were independent prognostic factors for overall survival, whereas one liver metastasis (vs. no liver metastasis) was not. The 5-year overall survival and median survival times in those with one liver metastasis with complete resection and a negative margin (40.9%, 28.3 months) were significantly better than those in patients with ≥2 liver metastases with complete resection and a negative margin (0%, 11.0 months, p = 0.025), and comparable to those in patients with liver metastasis with complete resection and a negative margin (37.0%, 33.0 months). According to the univariate analysis of resected patients with GBC and liver metastases (n=24), minor hepatectomy, less blood loss, less surgery time, papillary adenocarcinoma, T2, morbidity of Clavien–Dindo classification ≤ 2, and adjuvant chemotherapy were significantly associated with longer survival. Long-term survivors (n = 5) had a high frequency of T2 tumors (4/5), had small liver metastases near the gallbladder during or after surgery, underwent minor hepatectomy without post-operative complications, and received post-operative adjuvant chemotherapy.Conclusions: Although there is no surgical indication for GBC with liver metastasis diagnosed pre-operatively, minor hepatectomy and post-operative chemotherapy may be an option for selected patients with T2 GBC and liver metastasis identified during or after surgery who do not have other poor prognostic factors.

“How Long Have I Got?” in Stage IV NSCLC Patients With at Least 3 Months Up to 10 Years Survival, Accuracy of Long-, Intermediate-, and Short-Term Survival Prediction Is Not Good Enough to Answer This Question

BackgroundMost lung cancer patients worldwide [stage IV nonsmall cell lung cancer (NSCLC)] have a poor survival: 25%–30% die &lt;3 months. Yet, of those surviving &gt;3 months, 10%–15% (70,000–105,000 new patients worldwide per year) survive (very) long. Surprisingly, little scientific attention has been paid to the question, which factors cause the good prognosis in these NSCLC stage IV long survivors. Therefore, “How long do I still have?” currently cannot be accurately answered. We evaluated in a large group of 737 stage IV NSCLC patients surviving 3.2–120.0 months, the accuracies of short- and long-term survival predictive values of baseline factors, radiotherapy (RT), platinum-based chemotherapy (PBT), and tyrosine kinase inhibitor targeted therapy (TKI-TT).MethodsThis is a noninterventional study of 998 consecutive first-onset stage IV NSCLC patients. A total of 737 (74%) survived 3.2–120.0 months, 47 refused RT, PBT, and TKI-TT. Single and multivariate survival analysis and receiver operating curve (ROC) analysis were used with dead of disease (DOD) or alive with disease (AWD) as endpoints.ResultsThe median survival (16.1 months) of 47 patients who refused PBT, RT, and TKI-TT was significantly worse than those with RT, PBT, and/or TKI-TT (23.3 months, HR = 1.60, 95% CI = 1.06–2.42, p = 0.04). Of these latter 690 patients, 42% were females, 58% males, median age 63 years (range 27–85), 1-, 2-, 5-, and 10-year survival rates were 74%, 49%, 16%, and 5%. In total, 16% were alive with disease (AWD) at the last follow-up. Pathology subtype (adenocarcinoma vs. all others), performance score, TNM substage, the number of PBT cycles and TKI-TT had independent predictive value. However, with the multivariate combination of these features, identification results of short-term nonsurvivors and long-term survivors were poor.ConclusionsIn stage IV NSCLC patients with &gt;3 months survival, baseline features, and systemic therapeutic modalities have strong survival predictive value but do not accurately identify short- and long-term survivors. The predictive value of other features and interventions discussed should be investigated in the worldwide very large group of stage IV NSCLC patients with &gt;3 months survival.

Infectious complications and vaccines

Infections are a major cause of morbidity and can result in mortality in long-term survivors after allogeneic hematopoietic cell transplantation. Chronic graft-versus-host disease and delayed immune reconstitution are recognized risk factors. Different strategies must be utilized depending on the individual patient's situation but include prolonged antimicrobial prophylaxis and vaccination. Some important infections due to pathogens preventable by vaccination are pneumococci, influenza, varicella-zoster virus, and SARS-CoV-2. Despite the fact that such recommendations have been in place for decades, implementation of these recommendations has been reported to be poor.

BT-4 The treatment history of long-term survivors of Optic Pathway Glioma in Kobe Children’s Hospital

Optic pathway glioma(OPG) is almost recognized in childhood and about 0.01–0.02% of whole brain tumor in Japan. Because of the rare tumor, there are few reports about results of its treatment. In 2021, Guideline of Optic pathway/hypothalamic glioma is indicated from The japan Society for Neuro-Oncology. We retrospectively study 9 cases history of OPG who have treated for more than 5 years from January 2005 to March 2021 in Kobe Children’s Hospital. Cases are 4 boys and 5 girls. Average age at diagnosis is 3.8 years old and average follow up term is 11 years 10 months. They are 4 Pilocytic astrocytoma, 3 Pilomyxoid astrocytoma, and 1 Fibrillary astrocytoma. Al l cases have survived. There are only 2 cases who could be controlled with single series of surgical treatment and chemotherapy. Most cases need several times of resection and chemotherapy and uncontrollable 5 cases required radiological treatment. 2 cases are still under treatment for over 10 years. For OPG, partial resection to control hydrocephalus is recommended and several trial of chemotherapy must be carried out. There exist a few cases who need continuous treatment for long term. The other side, a few cases are uncontrollable those need radiotherapy to manage tumor volume. Because the history of OPG would be long term, we should adjust the treatment plan to environment of patients.

Impaired right ventricular function in long-term survivors of allogeneic haematopoietic stem-cell transplantation

AimsSurvivors of allogeneic haematopoietic stem-cell transplantation (allo-HSCT) are at higher risk of cardiovascular disease. We aimed to describe right ventricular (RV) systolic function and risk factors for RV dysfunction in long-term survivors of allo-HSCT performed in their youth.Methods and resultsThis cohort included 103 survivors (53% female), aged (mean±SD) 17.6±9.5 years at allo-HSCT, with a follow-up time of 17.2±5.5 years. Anthracyclines were used as first-line therapy for 44.7% of the survivors. The RV was evaluated with echocardiography, and found survivors to have reduced RV function in comparison to a group of healthy control subjects: Tricuspid annular plane systolic excursion, (TAPSE, 20.8±3.7 mm vs 24.6±3.8 mm, p<0.001), RV peak systolic velocity (RV-s’, 11.2±2.3 cm/s vs 12.3±2.3 cm/s, p=0.001), fractional area change (FAC, 41.0±5.2% vs 42.2±5.1%, p=0.047) and RV free-wall strain (RVFWS, −27.1±4.2% vs −28.5±3.3%, p=0.043). RV systolic dysfunction (RVSD) was diagnosed in 14 (13.6%), and was strongly associated with progressive left ventricular systolic dysfunction (LVSD). High dosages of anthracyclines were associated with greater reductions in RV and LV function. Multivariable linear regressions confirmed global longitudinal strain to be a significant independent predictor for reduced RV function.ConclusionImpaired RV function was found in long-term survivors of allo-HSCT who were treated in their youth. This was associated with progressive left ventricle dysfunction, and pretransplant therapies with anthracyclines. The occurrence of RVSD was less frequent and was milder than coexisting LVSD in this cohort.

Long-Term Follow-Up of Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation (HSCT) offers the opportunity for cure to patients with malignant and non-malignant diseases. Given the myriad advances in the past few decades, coupled with the rising numbers of transplants worldwide, the number of long-term survivors, many of whom are free of the disease for which they were transplanted, is constantly increasing. Despite the improved prognosis observed overall, long-term outcome may be undermined by transplant-associated morbidity and mortality. Long-term survivors may present a variety of complications, comprising physical, psychological, social, and economic arenas, with a deep impact on quality of life. Therefore, drawing greater attention to and raising awareness of the potential long-term effects of HSCT is key to providing a tailored approach to pretransplant counseling and to devising appropriate recommendations for post-transplant screening, prevention, and timely treatment of secondary events. In 2020, the Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society for Blood and Marrow Transplantation and Cellular Therapy (SBTMO) convened a task force to provide updated, evidence-based guidance for the long- term follow-up of pediatric patients undergoing HSCT, the results of which are presented here.

The Potential Prognostic Value of a Novel Hematologic Marker Fibrinogen-to-Lymphocyte Ratio in Head and Neck Adenoid-Cystic Carcinoma

Many patients with adenoid-cystic carcinoma (ACC) experience an indolent course of disease over many years but face late recurrence, and long-term survivors are rare. Due to its infrequent occurrence, it is hard to predict outcome in these patients. The fibrinogen-to-lymphocyte ratio (FLR) was recently proposed as an outcome prognosticator in different cancer entities. We aimed to investigate its prognostic relevance in patients with head and neck ACC. This retrospective analysis was performed including all patients treated for ACC between 1998 and 2020. The FLR ratio was calculated based on pretreatment values (0–7 days). The study cohort was dichotomized based on optimized threshold value and compared for differences in outcome (overall survival (OS) and disease-free survival (DFS)). In the cohort of 39 included patients, the OS was significantly longer in the low (n = 28) compared to the high pretreatment FLR group (n = 11) (median OS 150.5 months, 95% confidence intervals (CI) 85.3–215.7 months vs. 29.4 months, 95% CI not reached; p = 0.0093). Similarly, the DFS was significantly longer in the low FLR group (median DFS 74.5 months, 95% CI 30.6–118.4 months vs. 11.0 months, 95% CI 5.1–16.9 months; p = 0.019). The FLR is an easily obtainable and simple marker and may be a valuable outcome prognosticator in patients with ACC. Further studies are needed for validation of our results.