Treatment of Older Adult Patients with Glioblastoma: Moving towards the Inclusion of a Comprehensive Geriatric Assessment for Guiding Management

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, and over half of patients with newly diagnosed GBM are over the age of 65. Management of glioblastoma in older patients includes maximal safe resection followed by either radiation, chemotherapy, or combined modality treatment. Despite recent advances in the treatment of older patients with GBM, survival is still only approximately 9 months compared to approximately 15 months for the general adult population, suggesting that further research is required to optimize management in the older population. The Comprehensive Geriatric Assessment (CGA) has been shown to have a prognostic and predictive role in the management of older patients with other cancers, and domains of the CGA have demonstrated an association with outcomes in GBM in retrospective studies. Furthermore, the CGA and other geriatric assessment tools are now starting to be prospectively investigated in older GBM populations. This review aims to outline current treatment strategies for older patients with GBM, explore the rationale for inclusion of geriatric assessment in GBM management, and highlight recent data investigating its implementation into practice.

Experience with stereotaxis in patient with local relapse of neuroblastoma in central nervous system in context of combination therapy

Neuroblastoma is a complicated systemic malignant process that requires risk-adapted, multimodal therapy. Certainly, the dissemination of the tumor process is an extremely unfavorable prognosis for the patient’s life and health, however, local relapses can be cured successfully. The aim of the article is to demonstrate a rare clinical case of using SBRT in a patient with central nervous system neuroblastoma local relapse in the context of combined modality treatment.

Clinical efficacy of linagliptin combined with irbesartan in patients with diabetic nephropathy

Objective: To determine the clinical efficacy of linagliptin combined with irbesartan in patients with diabetic nephropathy (DN). Methods: Seventy-two patients who were admitted to our department of endocrinology in our hospital during January 2018 and June 2019 were randomly divided into a control group (administered with irbesartan only, n=36) and a treatment group (treated with irbesartan and linagliptin, n=36). The course of treatment lasted for three months. FBG (fasting blood glucose), 2hPBG (2h postprandial blood sugar), HbA1C (hemoglobin A1c), Cys-C (cystatin C), SCr (serum creatinine), BUN (blood urea nitrogen), UACR (urine albumin-to-creatinine ratio), CRP (C-reactive protein), IL-6 (interleukin-6), and SOD (superoxide dismutase) were tested pre- and post-treatment to evaluate the clinical efficacy and adverse effects of the two treatment plans after three months of treatment. Results: Compared with the pre-treatment levels, FBG, 2hPBG, HbA1c, Cys-C, SCr, BUN, UACR, CRP, IL-6, and SOD in both groups were significantly improved following the three-month treatment (P<0.05, respectively). Post-treatment levels of FBG, 2hPBG, HbA1c, Cys-C, SCr, BUN, UACR, CRP, and IL-6 in the treatment group were significantly lower than in the control group (P<0.05, respectively), while the treatment group exhibited a higher level of SOD compared with the control group (P<0.05). No serious adverse reaction occurred in either group (P>0.05). Conclusion: Combined-modality treatment with linagliptin and irbesartan shows favorable clinical efficacy in treating diabetic nephropathy as it effectively protects the kidneys and improves kidney function by inhibiting inflammatory and oxidative stress responses. doi: https://doi.org/10.12669/pjms.38.1.4417 How to cite this:Liu J, Zhang J, Hou M, Du W. Clinical efficacy of linagliptin combined with irbesartan in patients with diabetic nephropathy. Pak J Med Sci. 2022;38(1):---------. doi: https://doi.org/10.12669/pjms.38.1.4417 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Single-Agent Rituximab and Ultra-Low-Dose Adaptive Radiotherapy for the Treatment of Indolent Non-Hodgkin Lymphoma

Introduction For indolent non-Hodgkin lymphoma (NHL), there is level 1 evidence (FoRT) demonstrating superior long term local control with 24 Gy radiation treatment (RT) over ultra-low-dose 4 Gy RT (Hoskin et al Lancet 2021). However, it's notable that over 2/3 of those receiving ultra-low-dose RT did achieve durable local control. Further, with RT alone to any dose, the predominant pattern of failure is distal. Thus, the TROG study showed that the addition of systemic therapy (rituximab, cyclophosphamide, vincristine) after RT (30 Gy) significantly improved progression free survival (PFS). However, cytotoxic chemotherapy and higher dose RT can both cause significant, and potentially unnecessary, toxicities. We hypothesize that for indolent NHL, the combination of single-agent rituximab and ultra-low-dose adaptive RT, with repeat treatment as needed, will result in excellent local and systemic disease control with minimal toxicities. Methods We conducted an IRB approved, retrospective review of patients with indolent NHL who were treated with both ultra-low-dose RT (2 Gy x 2 or "boom boom") and single-agent rituximab (4 cycles) either concurrently or within a short interval (median 13 days) at our institution from 2017-2020. 17 treatments [follicular (9), marginal zone (4), mucosal associated lymphoid tissue (3), other (1)] from 15 patients were identified. Treatment sites included pelvis (5), parotid (4), abdomen (4), mediastinum (1), and other (3). The median ECOG performance status was 1 (range: 0-2), the median age was 74 (range: 25-90), and 9/15 patients were male. 7 patients were stage I, 5 stage II, 2 stage III, and 1 stage IV. 3 patients had prior RT with 1 patient having the same spot irradiated twice, and the other 2 both having RT at 2 distal sites. Only 1 patient had prior systemic treatment (ibrutinib) for their low-grade lymphoma. The primary outcomes were rates of complete response (CR), partial response (PR), overall response (defined as CR or PR), stable disease (SD), or progressive disease (PD). Secondary outcomes included PFS, overall survival (OS), symptom relief, and acute and long-term toxicities. Radiographic studies (predominantly PET/CT) were used to determine treatment response and disease control. Results In our cohort with median follow up of 16 months, the PFS and OS at one year was 93% (14/15)and 100% (15/15), respectively. The overall response rate was 94% (16/17), of which 13 sites (76%) achieved CR, 3 (18%) had PR, and 1 (6%) had SD. Of those with PR, 1 had residual disease in the field of RT, 1 outside the field of RT, and 1 both in and out of the field of RT. For the first 2, repeat ultra-low-dose RT was given to sites of PR and both achieved CR. The remaining patient with both in and out of field PR was managed with active surveillance with SD on last follow up. 2 patients experienced acute toxicities, 1 with mild diarrhea from pre-sacral RT that resolved within days, and 1 with dysgeusia from parotid RT that resolved within 2 months. Only 1 patient noted long-term toxicity of dry mouth with about 50% reduction in saliva after left parotid gland RT, but of note this patient also had preexisting Sjogren's syndrome. Symptoms were present in 10 patients, of which 9 noted improvement after treatment. The only patient whose symptoms did not improve was the patient with SD. This patient had neuro involvement of the lymphoma with multiple confounding factors. Conclusion Combined modality treatment with single-agent rituximab and ultra-low-dose adaptive RT, with retreatment as needed, in patients with indolent NHL appears to provide effective palliation and disease control with minimal toxicity. For patients with concerns for radiation or chemotherapy related toxicity, this presents an attractive alternate treatment paradigm that warrants further evaluation in larger prospective studies. Disclosures Desai: Boston Scientific: Consultancy, Research Funding. Awan: ADCT therapeutics: Consultancy; Cardinal Health: Consultancy; Merck: Consultancy; BMS: Consultancy; Dava Oncology: Consultancy; Johnson and Johnson: Consultancy; Beigene: Consultancy; Incyte: Consultancy; Verastem: Consultancy; MEI Pharma: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; Kite pharma: Consultancy; Gilead sciences: Consultancy; Pharmacyclics: Consultancy; Janssen: Consultancy; Abbvie: Consultancy; Astrazeneca: Consultancy; Genentech: Consultancy.

EVALUATION OF THE QUALITY OF LIFE IN PATIENTS WITH LUNG CARCINOMA AFTER PNEUMONECTOMY

Background. Pneumonectomy is one of the most traumatic thoracic surgeries, leading to a significant decrease in the patient’s functional status. Despite numerous questionnaires, there is no standard approach to the study of the quality of life of patients who have undergone radical surgery for lung cancer.The purpose of the study was to conduct a retrospective analysis of the quality of life of patients who underwent pneumonectomy during the period 2017–2018, taking into account the extent of surgery, presence of concomitant disease and adjuvant antitumor treatment.Material and Methods. Changes in the quality of life (qol) during combined modality treatment were evaluated in 40 patients with non-small cell lung cancer. To assess the functional status, the criteria adopted for determining the surgical risk were used. The st. George`s Respiratory Questionnaire (sgrq) and Quality Outcomes study short-Form 36 (sf-36) were used to assess the respiratory system of patients. Data collection was carried out 12 months after surgery using a questionnaire method based on a direct survey of respondents.Conclusion. Postoperative special treatment significantly worsens both the functional parameters of patients and the quality of life. Thus, a multidisciplinary approach to the management of patient with participation of an oncologist, pulmonologist, physiotherapist, and rehabilitologist is required.

The Trend of Combined Modality Treatment and its Outcomes in Elderly Patients With Primary CNS Lymphoma; A 12-Year Population-Based Analysis Using Propensity Score

BackgroundThe addition of radiation to chemotherapy in elderly patients with PCNSL remains controversial. Our objective was to assess the trend of combined modality treatment (CMT) and compare its survival with chemotherapy alone and radiation alone in non-HIV patients. MethodsWe identified 6,537 patients who received single treatment modality, combined modality treatment, or no treatment at all between 2004 and 2015 from the National Cancer Database. Factors affecting treatment selection were investigated using a logistic regression model. Annual percentage change (APC) was calculated to assess the trend of CMT use. A propensity score weighting methodology was used to compare survival outcomes. FindingsOnly 12.8% of patients received CMT, and this proportion steadily declined between 2004 (17.7%) and 2015 (8.7%), with APC of -6.0% (95% CI -8.0 to -4.0, p-value <0.001) during the 12 years. Apart from classical prognostic factors (age and comorbidities), treatment selection was significantly influenced by sex, facility type, degree of urbanization, and type of insurance. CMT had improved survival (median overall survival 19.5 months (95% CI 15.7-22.8)) compared with single-modality treatment. This effect was more prominent in the first year. Conclusion Socioeconomic factors affect the selection of treatment in elderly patients with PCNSL that can alter outcomes. CMT is falling out of favor in this patient population due to the risks of neurotoxicity. Further work should focus on developing strategies that minimize toxicity and access disparities without compromising survival

Outcomes of curative intent treatment in advanced gynecological cancer with recurrent, distant lymph node, or visceral organ metastasis: Retrospective study from a single community center.

e17566 Background: Uterine, cervical and ovarian cancers with isolated recurrences in the pelvic, para-aortic or distant lymph nodes, such as axillary, supraclavicular lymph node, or visceral organs, are uncommon conditions. The standard care is palliative systemic chemotherapy. We hypothesized that combined modality treatment (CMT) incorporating surgery or radiation for curative intent may increase local disease control and delay or mitigate further distant metastasis, thereby increase overall survival (OS). Methods: We retrospectively reviewed characteristics and outcomes of patients who had localized recurrence of gynecological malignancies and who were treated with an aggressive approach of salvage chemotherapy + radiation +/- surgery or radiofrequency ablation. Results: We identified 23 patients, including 6 cervical, 14 uterine and 3 ovarian cancer patients who were treated from 2005 to 2021. The mean age was 68. About 47.8% patients had advanced stages of disease at diagnosis (stage 3+4). Serous carcinoma (n = 7, 30.4%) was the most common uterine cancer pathology. All patients received curative intent therapy at initial diagnosis. The first recurrence sites are shown in the table, and the visceral organs involvement were liver, gluteal muscle, etc. The recurrence was within previous radiation field in 9 patients (39.1%) and outside radiation field in 12 (52.1%). 16 patients had local radiation + chemo, 6 had systemic chemo only and 1 had radiation only (see table below). Only 13 patients had a second recurrence, including 5 from the previous systemic treatment only group. Seven had local recurrence only and all received local therapy. Six patients eventually developed wide spread disease, and 2 died. After a median follow up of 56 months (range 22 to 186 months), 17 patients were alive (4 lost for follow up), and 15 had no evidence of disease (NED). The median time to first recurrence was 14.5 m [Interquartile range (IQR), Q1, Q3 to be 7, 19]. The PFS for those patients who had only 1 recurrence was 41.5 m (IQR 21, 63). The PFS for those who had the second recurrence until the next progression was 15 months (IQR 9, 37). The overall survival in all patients was 56 m (IQR 39, 71). Conclusions: A curative intent, salvage CMT protocol for advanced GYN cancer patients who develop isolated local or distant recurrence may have a therapeutic advantage. It renders a longer PFS and OS than those from systemic therapy alone reported in the historical data.[Table: see text]