Predictors for Adherence to Treatment Strategies in Elderly HNSCC Patients

Finding a cure may be less important than ensuring the quality of life in elderly patients with head and neck squamous cell carcinoma (HNSCC). The aim of this study was to determine predictors for adherence. Clinical and pathological data from patients ≥70 years with HNSCC (initial diagnoses 2004-2018) were investigated retrospectively. Evaluated clinical predictors included biological age (Charlson Comorbidity Index; CCI), patient health (Karnofsky Performance Status; KPS) and therapy data. A total of 1125 patients were included. The median age was 75 years, 33.1% reached CCI ≥6, and 53.7% reached KPS ≤ 70%. In total, 968 patients were adherent, whereas 157 were nonadherent. Nonadherent patients were significantly more often smokers (p = 0.003), frequent drinkers (p = 0.001), had a worse health status (p ≤ 0.001) and a lower biological age (p = 0.003), an advanced T classification and lymph node involvement or UICC stage (each p ≤ 0.001). Approximately 88.0% of the included patients received a curative treatment recommendation. A total of 6.9% discontinued the therapy, and 7.0% refused the therapy. With the increasing complexity of a recommended therapy, adherence decreased. The 5-year overall survival was significantly higher in adherent patients (45.1% versus 19.2%). In contrast to the chronological patient age, biological age is a significant predictor for adherence. The evaluated predictors for nonadherence need to be verified prospectively.

Primary systemic therapy for patients with brain metastases from lung cancer ineligible for targeted agents

Purpose The purpose of this study was to evaluate overall survival after systemic therapy, largely chemotherapy, in patients with small cell or non-small cell lung cancer and brain metastases. After completion of systemic therapy, some patients received planned brain irradiation, while others were followed. Methods Retrospective cohort study. Results Thirty-eight patients were included (28 small cell, 20 followed with imaging). Six of these 20 patients (30%) received delayed radiotherapy during follow-up. Planned radiotherapy (n = 18, intention-to-treat) was associated with longer survival from diagnosis of brain metastases, median 10.8 versus 6.1 months, p = 0.025. Delayed radiotherapy still resulted in numerically better survival than no radiotherapy at all (median 8.8 versus 5.3 months, not significant). If calculated from the start of delayed radiotherapy, median survival was only 2.7 months. In a multivariable analysis, both Karnofsky performance status ≥ 70 (p = 0.03) and planned radiotherapy (p = 0.05) were associated with better survival. Conclusion In patients ineligible for targeted agents, planned radiotherapy in a modern treatment setting was associated with longer survival compared to no radiotherapy. Timing and type of radiotherapy in such patients should be evaluated in prospective trials to identify patients who might not need planned radiotherapy.

Barriers to and Facilitators of Return to Work in Head and Neck Cancer Patients with in the First Six Months Post-Treatment

Objective To identify the factors associated with barriers to and facilitators of return to work (RTW) in head and neck cancer (HNC) patients in the first six months post-treatment. Methods This cross-sectional study examined HNC patients who completed treatment from the outpatient radiation department of a single cancer center in northern Taiwan from October 2018 to July 2020. Demographic and clinical characteristics were recorded, and patients were assessed using the Return to Work Barrier Scale, Return to Work Facilitator Scale, Distress Thermometer, Numeric Rating Scale, and Karnofsky Performance Status Scale questionnaires. Results Of the 106 HNC patients surveyed, 54.7% successfully RTW. Barriers to RTW included patient-perceived worst health status, greater symptom burden, and age ≥55 years. These factors explained 34.6% of the variance in overall barriers to RTW. Facilitators of RTW were lower psychological distress and who did not receive reconstruction surgery. These factors explained 17.9% of the variance in facilitators to RTW. Conclusion Patient-perceived health status and age most strongly influence RTW in HNC patients. HNC patients who can RTW should be encouraged to do so, and clinician awareness of potential barriers can aid patients in their RTW.

The Efficacy of Temozolomide Combined with Levetiracetam for Glioblastoma (GBM) After Surgery: a Study Protocol for a Double-Dlinded and Randomized Controlled Trial

Background: Temozolomide is applied as the standard chemotherapy agent in patients with glioblastoma (GBM) after surgery. However, the benefit of this treatment for patients is limited by the invasive growth of glioma and drug resistance. There are indications from fundamental experimental and retrospective studies that levetiracetam has the potential to improve the survival rate of GBM patients. However, it has yet to be ascertained whether the combination of temozolomide and levetiracetam is more effective than temozolomide chemotherapy alone. Therefore, we designed a randomized clinical trial to investigate the therapeutic effect of the new combined regime for the treatment of GBM.Methods/design: This is a double-blind and randomized clinical trial carried out in a single center. A total of 142 patients will be recruited and screened for the inclusion and exclusion criteria. Then, eligible participants will be enrolled and randomly allocated into an Experimental group or a Control group in a 1:1 ratio. Based on the administration of radiation therapy (RT), participants in the Experimental group will be prescribed levetiracetam plus temozolomide chemotherapy for 34 weeks while participants in the Control group will be prescribed placebo tablets plus temozolomide for the same duration. All patients will be followed-up for three years after intervention. Accordingly, the primary outcome will be progression-free survival (PFS). The secondary endpoints include overall survival (OS), the Karnofsky Performance Status (KPS), the objective response rate (ORR), and the incidence of adverse events. Discussion: The results of this trial are expected to provide high-level evidence regarding the clinical benefits of the combination of levetiracetam and temozolomide in the treatment of GBM.Trial registration: www.ChiCTR.org.cn, ID: ChiCTR-2100049941. Registered on 14thAugust 2021.

Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline

Purpose To provide guidance to clinicians regarding therapy for patients with brain metastases from solid tumors. Methods ASCO convened an Expert Panel and conducted a systematic review of the literature. Results Thirty-two randomized trials published in 2008 or later met eligibility criteria and form the primary evidentiary base. Recommendations Surgery is a reasonable option for patients with brain metastases. Patients with large tumors with mass effect are more likely to benefit than those with multiple brain metastases and/or uncontrolled systemic disease. Patients with symptomatic brain metastases should receive local therapy regardless of the systemic therapy used. For patients with asymptomatic brain metastases, local therapy should not be deferred unless deferral is specifically recommended in this guideline. The decision to defer local therapy should be based on a multidisciplinary discussion of the potential benefits and harms that the patient may experience. Several regimens were recommended for non–small-cell lung cancer, breast cancer, and melanoma. For patients with asymptomatic brain metastases and no systemic therapy options, stereotactic radiosurgery (SRS) alone should be offered to patients with one to four unresected brain metastases, excluding small-cell lung carcinoma. SRS alone to the surgical cavity should be offered to patients with one to two resected brain metastases. SRS, whole brain radiation therapy, or their combination are reasonable options for other patients. Memantine and hippocampal avoidance should be offered to patients who receive whole brain radiation therapy and have no hippocampal lesions and 4 months or more expected survival. Patients with asymptomatic brain metastases with either Karnofsky Performance Status ≤ 50 or Karnofsky Performance Status < 70 with no systemic therapy options do not derive benefit from radiation therapy. Additional information is available at www.asco.org/neurooncology-guidelines.

Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline

PURPOSE To provide guidance to clinicians regarding therapy for patients with brain metastases from solid tumors. METHODS ASCO convened an Expert Panel and conducted a systematic review of the literature. RESULTS Thirty-two randomized trials published in 2008 or later met eligibility criteria and form the primary evidentiary base. RECOMMENDATIONS Surgery is a reasonable option for patients with brain metastases. Patients with large tumors with mass effect are more likely to benefit than those with multiple brain metastases and/or uncontrolled systemic disease. Patients with symptomatic brain metastases should receive local therapy regardless of the systemic therapy used. For patients with asymptomatic brain metastases, local therapy should not be deferred unless deferral is specifically recommended in this guideline. The decision to defer local therapy should be based on a multidisciplinary discussion of the potential benefits and harms that the patient may experience. Several regimens were recommended for non–small-cell lung cancer, breast cancer, and melanoma. For patients with asymptomatic brain metastases and no systemic therapy options, stereotactic radiosurgery (SRS) alone should be offered to patients with one to four unresected brain metastases, excluding small-cell lung carcinoma. SRS alone to the surgical cavity should be offered to patients with one to two resected brain metastases. SRS, whole brain radiation therapy, or their combination are reasonable options for other patients. Memantine and hippocampal avoidance should be offered to patients who receive whole brain radiation therapy and have no hippocampal lesions and 4 months or more expected survival. Patients with asymptomatic brain metastases with either Karnofsky Performance Status ≤ 50 or Karnofsky Performance Status < 70 with no systemic therapy options do not derive benefit from radiation therapy. Additional information is available at www.asco.org/neurooncology-guidelines .

Preoperative Thrombocytosis is Not Associated with Overall Survival in 309 Glioblastoma Patients

Background In recent years, a correlation of thrombocytosis and a worse prognosis was shown for many solid cancers, including glioblastoma multiforme (GBM). Methods A retrospective review was performed for all patients with a histologically proven and first-diagnosed GBM between 2005 and 2015 in our department. Clinical and paraclinical parameters were acquired from patient documentation and structured for subsequent data analysis. The association of potential risk factors with overall survival was assessed using the Kaplan–Meier survival analysis and Cox regression. Results The present study includes 309 patients first diagnosed with primary GBM. Our analyses validate well-known risk factors of a decreased overall survival such as higher patient age, a larger preoperative tumor volume, Karnofsky performance status, extent of resection, tumor localization, and adjuvant treatment. However, no correlation was observed between a preoperative thrombocytosis, the mean platelet volume, leucocyte count, activated partial thromboplastin time (apTT), fibrinogen level, and acetylsalicylic acid 100 co-medication. Patients with preoperative hemoglobin below 7.5 mmol/L had decreased overall survival. Conclusion The present study, enrolling the largest numbers of patients assessing this topic to date, did not find any association between a preoperative thrombocytosis and overall survival in 309 patients with GBM.

STMO-12 Efforts for safe malignant brain tumor surgery at our hospital

Although maximal safe resection is the current standard for glioblastoma surgery, its safety and removal rate conflict with each other. Electrophysiological monitoring, such as motor evoked potential monitoring and awake craniotomy, can be utilized as safety measures; not all facilities can perform them. Herein, we present a representative case report on our efforts for a safe malignant brain tumor surgery. Case: A 77-year-old woman with glioblastoma in the premotor cortex presented with seizure of the upper left lower limb. Her pyramidal tract ran from the medial bottom to the posterior of the tumor. We performed excision from the site using the lowest gamma entropy. We then removed all parts of the tumor, with the exception of the pyramidal tract infiltration, and no paralysis was observed. She was definitively diagnosed with glioblastoma and is currently on maintenance chemotherapy. As a preoperative examination, we performed cerebrovascular angiography. We then performed various other tests to ascertain the patient’s condition. Considering lesions that affect language, Wada tests were performed regardless of laterality. For all patients with epilepsy onset, preoperative 256-channel electroencephalogram measurement and intraoperative the gamma entropy analysis were performed to confirm epileptogenicity. Considering lesions that affect eloquence, subdural electrodes were placed and brain function mapping was performed the next day. Based on the results, the safest cortical incision site and excision range were determined, and excision was performed on the following day. Of the 14 operated glioblastoma cases after November 2018, more than 85% of the contrast-enhanced lesions were completely removed in 7 cases, partially removed in 5 cases, and underwent biopsy in 2 cases. Postoperative Karnofsky performance status scores remained unchanged in 11 cases, improved in 1 case, and deteriorated in 2 cases. Our efforts have resulted in safe and sufficient removal of malignant brain tumors during surgery.

Proliferating CD8+ T Cell Infiltrates Are Associated with Improved Survival in Glioblastoma

Background: tumor-infiltrating lymphocytes are prognostic in many human cancers. However, the prognostic value of lymphocytes infiltrating glioblastoma (GBM), and roles in tumor control or progression are unclear. We hypothesized that B and T cell density, and markers of their activity, proliferation, differentiation, or function, would have favorable prognostic significance for patients with GBM. Methods: initial resection specimens from 77 patients with IDH1/2 wild type GBM who received standard-of-care treatment were evaluated with multiplex immunofluorescence histology (mIFH), for the distribution, density, differentiation, and proliferation of T cells and B cells, as well as for the presence of tertiary lymphoid structures (TLS), and IFNγ expression. Immune infiltrates were evaluated for associations with overall survival (OS) by univariate and multivariate Cox proportional hazards modeling. Results: in univariate analyses, improved OS was associated with high densities of proliferating (Ki67+) CD8+ cells (HR 0.36, p = 0.001) and CD20+ cells (HR 0.51, p = 0.008), as well as CD8+Tbet+ cells (HR 0.46, p = 0.004), and RORγt+ cells (HR 0.56, p = 0.04). Conversely, IFNγ intensity was associated with diminished OS (HR 0.59, p = 0.036). In multivariable analyses, adjusting for clinical variables, including age, resection extent, Karnofsky Performance Status (KPS), and MGMT methylation status, improved OS was associated with high densities of proliferating (Ki67+) CD8+ cells (HR 0.15, p < 0.001), and higher ratios of CD8+ cells to CD4+ cells (HR 0.31, p = 0.005). Diminished OS was associated with increases in patient age (HR 1.21, p = 0.005) and higher mean intensities of IFNγ (HR 2.13, p = 0.027). Conclusions: intratumoral densities of proliferating CD8 T cells and higher CD8/CD4 ratios are independent predictors of OS in patients with GBM. Paradoxically, higher mean intensities of IFNγ in the tumors were associated with shorter OS. These findings suggest that survival may be enhanced by increasing proliferation of tumor-reactive CD8+ T cells and that approaches may be needed to promote CD8+ T cell dominance in GBM, and to interfere with the immunoregulatory effects of IFNγ in the tumor microenvironment.

Influencing factors of depressive symptoms in patients with malignant tumour

Objective To assess the influencing factors of depressive symptoms in malignant tumour patients. Methods Participants were 2079 inpatients with malignant tumour (1291: depressive symptoms; 788 no depressive symptoms). Univariable and multivariable logistic regression were used to evaluate sociodemographic and clinical factors influencing depressive symptoms. Results Risk factors were family income ≤5000 yuan (odds ratio [OR]: 4.966, 95% confidence interval [CI]: 2.938–8.395) and 5001–10,000 yuan (OR: 3.111, 95% CI: 1.840–5.260); Karnofsky Performance Status of 70 (OR: 2.783, 95% CI: 1.281–6.042) and 80 (OR: 1.834, 95% CI: 1.139–2.953); disease course ≤1 year; palliative treatment (OR: 2.288, 95% CI: 1.292–4.055); progressive disease (OR: 1.876, 95% CI: 1.284–2.739); pain (OR: 1.973, 95% CI: 1.555–2.505); cancer type: lung (OR: 3.199, 95% CI: 1.938–5.279), oesophagus (OR: 3.288, 95% CI: 1.673–6.464), cervix (OR: 1.542, 95% CI: 1.056–2.253) and partial knowledge of disease condition (OR: 2.366, 95% CI: 1.653–3.385). Return to work (OR: 0.503, 95% CI: 0.348–0.727) and physical exercise (OR: 0.437, 95% CI: 0.347–0.551) were protective against depressive symptoms. Conclusions Several factors affected depressive symptoms in malignant tumour patients, including income, disease type and course, palliative treatment, return to work and physical exercise.