The prognostic impact of substantial lymphovascular space invasion in women with node negative FIGO stage I uterine carcinoma.

OBJECTIVE: Substantial lymphovascular space invasion (LVSI) is an important predictor of lymph node (LN) involvement in women with endometrial carcinoma. We studied the prognostic significance of substantial LVSI in patients with 2009-FIGO stage-I uterine endometrioid adenocarcinoma (EC) who all had pathologic negative nodal evaluation (PNNE). METHODS: Pathologic specimens were retrieved and LVSI was quantified (focal or substantial) in women with stage-I EC who had a hysterectomy and PNNE. In addition to multivariate analysis (MVA), recurrence-free (RFS), disease-specific (DSS), and overall (OS) survival was compared between women with focal vs. substantial LVSI. RESULTS: 1052 patients were identified with a median follow-up of 9.7 years. 358 women (34%) received adjuvant radiotherapy. 907 patients (86.2%) had no LVSI, 87 (8.3%) had focal, and 58 (5.5%) had substantial LVSI. Five-year RFS was 93.3% (95% CI: 91.5-95.1), 76.8% (95% CI: 67.2-87.7) and 79.1% (95% CI: 67.6-95.3) for no, focal, and substantial LVSI(p < 0.0001). There was no statistically significant difference in 5-year RFS, DSS, OS, and in the patterns of initial recurrence between women with focal vs substantial LVSI. On MVA with propensity score matching, substantial LVSI was not independently associated with any survival endpoint compared to focal LVSI, albeit both were detrimental when compared to no LVSI. Age ≥ 60 years and higher grade were predictors of worse RFS, DSS, and OS. Additionally, comorbidity burden was an independent predictor for OS. CONCLUSIONS: Our results suggest that substantial LVSI does not predict worse survival endpoints or different recurrence patterns in women with stage-I EC with PNNE when compared to focal LVSI.

Long-Term Follow-Up of Phase I Trial of Oncolytic Adenovirus-Mediated Cytotoxic and Interleukin-12 Gene Therapy for Treatment of Metastatic Pancreatic Cancer.

The long-term follow-up findings of the phase I trial evaluating the efficacy of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy in metastatic pancreatic cancer (mPC) seem very promising. The study employed a replication-competent Adenovector in combination with chemotherapy in a dose-escalation format. The trial demonstrated a clinically meaningful median overall survival (OS) benefit, with patients in the highest dose cohort exhibiting an impressive median OS of 18.4 months. This contrasts starkly with patients receiving lower doses who experienced a median OS of 4.8 and 3.5 months, respectively. Remarkably, subject number 10, who received the highest dose, demonstrated an extraordinary survival of 59.1 months, presenting a compelling case for further exploration. Additionally, this patient displayed complete responses in lung and liver metastases, a rare occurrence in mPC treatment. Statistical analyses supported the observed survival benefit. The unprecedented OS results emphasize the potential of this treatment strategy and pave the way for future investigations into this promising gene therapy approach.

CAR-T-Cell Therapy in Multiple Myeloma: B-Cell Maturation Antigen (BCMA) and Beyond.

Significant progress has been achieved in the realm of therapeutic interventions for multiple myeloma (MM), leading to transformative shifts in its clinical management. While conventional modalities such as surgery, radiotherapy, and chemotherapy have improved the clinical outcomes, the overarching challenge of effecting a comprehensive cure for patients afflicted with relapsed and refractory MM (RRMM) endures. Notably, adoptive cellular therapy, especially chimeric antigen receptor T-cell (CAR-T) therapy, has exhibited efficacy in patients with refractory or resistant B-cell malignancies and is now also being tested in patients with MM. Within this context, the B-cell maturation antigen (BCMA) has emerged as a promising candidate for CAR-T-cell antigen targeting in MM. Alternative targets include SLAMF7, CD38, CD19, the signaling lymphocyte activation molecule CS1, NKG2D, and CD138. Numerous clinical studies have demonstrated the clinical efficacy of these CAR-T-cell therapies, although longitudinal follow-up reveals some degree of antigenic escape. The widespread implementation of CAR-T-cell therapy is encumbered by several barriers, including antigenic evasion, uneven intratumoral infiltration in solid cancers, cytokine release syndrome, neurotoxicity, logistical implementation, and financial burden. This article provides an overview of CAR-T-cell therapy in MM and the utilization of BCMA as the target antigen, as well as an overview of other potential target moieties.

A Comparative Study of Hypofractionated and Conventional Radiotherapy in Postmastectomy Breast Cancer Patients.

OBJECTIVE: The aim of this study was to compare toxicity and locoregional control of short duration hypofractionated (HF) radiotherapy (RT) with conventional RT in breast cancer patients. METHODS: A total of 100 postmastectomy breast cancer patients were randomized for adjuvant RT in control group (comprising fifty patients who received the standard conventional dose of 50 Gy in 25 fractions with 2 Gy per fraction) and study group (comprising fifty patients who received HF RT with dose of 42.72 Gy in 16 fractions with 2.67 Gy per fraction). All patients were treated on linear accelerator with 3-dimensional conformal RT technique. Outcome was analyzed in terms of toxicity, tolerability, and locoregional control. RESULTS: In the present study, at a median follow-up of 20 months, almost similar results were seen in both the groups in terms of toxicity, tolerability, and locoregional control. Adjuvant postmastectomy HF RT was found to be well tolerated with mild-to-moderate side effects that neither reached statistical significance nor warranted any treatment interruption/hospitalization. CONCLUSIONS: HF postmastectomy RT is comparable to conventional RT without evidence of higher adverse effects or inferior locoregional tumor control and has an added advantage of increased compliance because of short duration; hence, it can help in accommodating more breast cancer patients in a calendar year, ultimately resulting in decreased waiting list, increased turnover, and reduced cost of treatment.

Compliance to radiotherapy: A tertiary care center experience.

CONTEXT: The most commonly prescribed conventional fractionation radiotherapy uses 1.8-2.2 Gy per fraction for five fractions in a week. Many times, unwanted interruptions are encountered, which ultimately affect the local control and overall survival. AIMS: The present retrospective study was carried out to study the compliance to radiotherapy at our institute and to determine various factors related to it. PATIENTS AND METHODS: The present retrospective study was carried out at the department of Radiotherapy, SMS Medical College and attached group of hospitals, Jaipur; in patients who were treated with curative intent with conventional fractionation radiotherapy over telecobalt machine from January 2017 to April 2017. Noncompliance was studied for association with various factors such as age, sex, site of primary disease, stage of tumor, distance patients had to travel to receive treatment, administration of concurrent chemotherapy, and financial burden of the treatment. RESULTS: Of 203 patients, 138 were of head-and-neck cancer, 42 of cervical cancer, and 23 of breast cancer. The cumulative incidence of noncompliance was 12.8% (15.9% for head-and-neck cancer, 7.2% for cervical cancer, and 4.4% for breast cancer). Statistically significant association was found between noncompliance and higher age of the patients (P = 0.07), male gender (P = 0.002), advanced stage (P = 0.004), administration of concurrent chemoradiotherapy (CCRT) (P < 0.001), and greater distance patients had to travel for radiotherapy (P = 0.03). CONCLUSIONS: The factors with which noncompliance is significantly associated in the present study are higher age, male gender, advanced stage of tumor, administration of CCRT, and greater distance patients had to travel to avail radiotherapy.

Breast cancer-related lymphedema in postmastectomy patients receiving adjuvant irradiation: A prospective study.

CONTEXT: In India, most breast cancer patients present with advanced stage requiring postmastectomy radiotherapy. Lymphedema is a long-term side effect that causes both physical and psychological distresses. AIMS: The present prospective study was carried out to study various factors affecting breast cancer-related lymphedema (BCRL). SUBJECTS AND METHODS: From January 2015 to March 2016, 100 postmastectomy patients who received adjuvant irradiation to chest wall were selected prospectively. Circumference of both arms was measured before surgery, at start, and at end of radiotherapy followed by 3 monthly intervals till last follow-up. Lymphedema was defined as a difference of ≥2 cm from the baseline in the arm circumference on the side of surgery. RESULTS: At a median follow-up of 24 months, the cumulative incidence of BCRL was 13%. On multivariate analysis, risk of BCRL was significantly associated with higher body mass index (BMI) (P = 0.004), greater number of lymph nodes (LNs) dissected (P = 0.005), higher nodal ratio (P = 0.006), and regional LN radiation (RLNR) (P = 0.048) but not with the type of fractionation (P = 0.094). CONCLUSIONS: Adjuvant RLNR, higher BMI, greater number of LNs dissected, and higher nodal ratio significantly increases the risk of development of BCRL. There was no significant difference in the lymphedema with the type of fractionation. Females receiving RLNR should be prospectively monitored for lymphedema to ensure early detection and possible intervention.

Hypofractionated Radiotherapy for Palliation in Locally Advanced Head and Neck Cancer.

CONTEXT: In India, a considerable proportion of patients with head and neck cancer present with locoregionally advanced disease. Symptom palliation becomes a major objective in these cases when they could not be considered for a curative approach. AIMS: The aim of this study is to assess the role of palliative radiotherapy for symptom control in patients with locally advanced head and neck cancer. SETTINGS AND DESIGN: This was a retrospective study. SUBJECTS AND METHODS: Between July 2015 and June 2016, 98 patients with stage IV head and neck cancer were treated with palliative radiotherapy 25 Gray (Gy)/4 fractions (fr)/1 fraction (6.25 Gy)/week. Presenting symptoms were noted. The primary end point was relief of symptoms in the 4th week after radiotherapy. Percentage symptom relief was quantified by the patient using a rupee scale. Treatment response was noted using the WHO criteria. Acute toxicity was graded as per the Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: The most common presenting symptom was pain. At 4 weeks after radiotherapy completion, all patients had >50% pain relief. Dysphagia was improved in 82% of patients. Respiratory distress was improved in all the symptomatic patients. Tumor complete response (CR) was seen in 2 patients, partial response in 89, stable disease in 3, and progressive disease in 4. RTOG Grade 2 and 3 acute skin and mucosal toxicities were seen in 29% and 27% cases, respectively. No patient had Grade 4 adverse effect. CONCLUSIONS: Hypofractionated radiation could provide effective symptom palliation in advanced head and neck cancers. The weekly schedule was well tolerated and found convenient by the patients.