Prognostic significance of delayed complete metabolic response on PET/CT after primary chemoradiation treatment of cervical cancer.

OBJECTIVE: To investigate the prognostic significance of near-complete metabolic response on initial follow-up PET/CT after primary chemoradiation treatment of cervical cancer. METHODS: Survival data were retrospectively compared between patients who had complete metabolic response on first follow-up PET/CT, 3 months after chemoradiation (group 1) with those who had near-complete metabolic response on first PET/CT and later showed complete metabolic response at subsequent PET/CT, 6 months or more after treatment (group 2). RESULTS: Of the 108 patients included in the final analysis, 74 (68.5%) showed complete metabolic response on initial PET/CT, 3 months after treatment, and 34 patients (31.5%) showed complete metabolic response on subsequent PET/CT, 6 months after treatment. Tumor characteristics were comparable between groups. Group 1 had higher percent of stage 1 (12% vs 0%) and lower percent of stage 4 disease (3% vs 14%) than those of group 2. Group 2 patients had significantly fewer cases of recurrences and deaths than group 1 patients (6% vs 26%, p=0.018; 0% vs 20%, p=0.003, respectively), with comparable 3-year survival rates (group 1, 90% vs group 2, 100%, p=0.31). Twelve patients had progressive disease on first follow-up PET/CT; these patients had significantly worse overall survival compared with all other patients (log-rank test, p<0.001). Younger age and delayed complete metabolic response were associated with lower chance of recurrence and death on univariate analysis. On multivariate analysis, delayed complete metabolic response remained significantly associated with no recurrence HR=0.14 (95% CI 0.25 to 0.84), p=0.031. CONCLUSIONS: Survival outcome of patients with cervical cancer who show residual 18F-fluorodeoxyglucose uptake on initial PET/CT after treatment, but reach complete metabolic response on follow-up PET/CT, is not inferior compared with survival of patients who show complete metabolic response on initial PET/CT 3 months after treatment. Watchful waiting with follow-up PET/CT seems a safe option for these patients.

Outcomes associated with treatment to all sites of disease in patients with stage IVB cancer of the cervix.

OBJECTIVE: The use of chemoradiation in patients with stage IVB cancer of the cervix was evaluated to determine if definitive treatment offers benefit. METHODS: A database of 546 patients with cancer of the cervix treated between January 2005 and May 2021 at a tertiary academic medical center was reviewed retrospectively to identify patients with stage IVB disease. Log rank test, regression analysis, and the Kaplan-Meier method were used to identify and compare variables and estimate progression free survival and overall survival. RESULTS: Thirty-three patients with stage IVB cervical cancer were identified. Median age was 53 years (range 28-78). Pathology subtypes were squamous cell (n=22, 67%), adenocarcinoma (n=8, 24%), and clear cell (n=3, 9%). Metastases were classified as lymphatic (n=14, 42%) or hematogenous (n=19, 58%). Following treatment to all sites with chemoradiotherapy and selected use of surgery (n=23), six patients (26%, lymphatic n=4, hematogenous n=2) remained disease free for a median duration of 4 years (range 3-17 years). Recurrences in the remaining patients were distant (n=13) or local (n=4). All patients in the chemotherapy group (n=10, 100%) progressed. Kaplan-Meier analysis showed that median progression free survival was longer for patients treated at all disease sites than for patients treated with chemotherapy alone (19 vs 11 months, p=0.01). However, this was not the case for overall survival (49 vs 33 months, p=0.15). Patients with metastases limited to lymph nodes also had longer median progression free survival (22 vs 11 months, p=0.04) but not overall survival (p=0.68). CONCLUSIONS: Patients with stage IVB cancer of the cervix may benefit from treatment to all sites of disease, if feasible and safe, as demonstrated by improved progression free survival.

Stereotactic Ablative Body Radiation for Stage I Lung Cancer in Israel: A Retrospective Single-Center Report.

BACKGROUND: Stereotactic ablative radiation therapy (SABR) is the application of a very high radiation dose to a small treatment volume. It is the new standard of care in medically inoperable early-stage lung cancer. OBJECTIVES: To report the outcomes of SABR in stage I lung cancer at Sheba Medical Center since its introduction in 2009. METHODS: We conducted a retrospective chart review of patients with stage I lung cancer treated during the period 2009-2015. Survival status was retrieved from the electronic medical records and confirmed with the national registry. Local failure was defined as increased FDG uptake on PETCT scan within a 2 cm radius of the treated region. Toxicity was estimated from medical records and graded according to common toxicity criteria for adverse events (CTCAE) version 4.03. Overall survival and local control were estimated by the Kaplan-Meier method. RESULTS: During the study period 114 patients were treated for 122 stage I lung cancer lesions. Median follow-up time was 27 months (range 8.2-69.5 months), median age was 76 years. Eighty-two percent of the tumors were stage IA (size ≤ 3 cm). Median survival was 46 months; estimated 3 year overall survival was 59% (95%CI 47-69%) and local control was 88% (95%CI 78-94%). Toxicity included chest wall pain in 8.4% of patients, rib fracture in 0.9%, grade 1-2 pneumonitis in 12%, grade 3 in 12% and grade 5 (death) in 0.9%. CONCLUSIONS: SABR has been successfully implemented at Sheba Medical Center for the treatment of stage I lung cancer in inoperable patients. It is associated with excellent local control, minor toxicity and an acceptable overall survival.

Neo-adjuvant Chemo-Radiation to 60 Gray Followed by Surgery for Locally Advanced Non-Small Cell Lung Cancer Patients: Evaluation of Trimodality Strategy.

BACKGROUND: Neoadjuvant chemo-radiation therapy (CRT) dosages in locally advanced non-small cell lung cancer (NSCLC) were traditionally limited to 45 Gray (Gy). OBJECTIVES: To retrospectively analyze outcomes of patients treated with 60 Gy CRT followed by surgery. METHODS: A retrospective chart review identified patients selected for CRT to 60 Gy followed by surgery between August 2012 and April 2016. Selection for surgery was based on the extent of disease, cardiopulmonary function, and response to treatment. Pathological response after neoadjuvant CRT was scored using the modified tumor regression grading. Local control (LC), disease free survival (DFS), and overall survival (OS) were estimated by the Kaplan-Meier method. RESULTS: Our cohort included 52 patients: 75% (39/52) were stage IIIA. A radiation dose of 60 Gy (range 50-62Gy) was delivered in 82.7%. Surgeries performed included: lobectomy, chest-wall resection, and pneumonectomy in 67.3%, 13.4%, and 19.2%, respectively. At median follow-up of 22.4 months, the 3 year OS was 74% (95% confidence interval [CI] 52-87%), LC was 84% (95%CI 65-93), and DFS 35% (95%CI 14-59). Grade 4-5 postoperative complications were observed in 17.3% of cases and included chest wall necrosis (5.7%), bronco-pleural fistula (7.7%), and death (3.8%). A major pathologic regression with < 10% residual tumor occurred in 68.7% of patients (36/52) and showed a trend to improved OS (P = 0.1). Pneumonectomy cases had statistically worse OS (P = 0.01). CONCLUSIONS: Major pathologic regression was observed 68.7% with 60 Gy neoadjuvant CRT with a trend to improved survival. Pneumonectomy correlated with worse survival.

The effect of long-standing lymphopenia after radiation therapy on survival in rectal cancer.

BACKGROUND: Lymphopenia and high neutrophil-to-lymphocyte ratio are known negative prognostic factors in rectal cancer. Until recently, however, lymphopenia was regarded as a minor sequela following radiation therapy (RT). The immune system's influence on rectal cancer treatment outcomes led us to evaluate the impact of lymphopenia at various time points, before, during, and following radiotherapy. We hypothesized that chronic lymphopenia following radiotherapy might negatively influence the survival of patients, and pre-treatment lymphopenia may be predictive of poor outcomes. METHODS: This retrospective study involved 110 patients treated for rectal cancer between 2015 and 2019. The oncological outcomes are defined as alive without disease (AWOD), alive with disease (AWD), and death. These outcome probabilities tested against variables of lymphopenia before RT, during RT, and at several post-RT follow-up time points. RESULTS: At the end of the study, 69 patients were AWOD (63 %), 13 were AWD (12 %) and 28 had died (25 %). Treatment results were assessed with according level of lymphocytes measured one year following RT: 35 out of 39 patients (89.7 %) with normal values were AWOD. In 65 patients with sustained lymphopenia, 52 % were AWOD, 18.5 % AWD and 29 % died. A similar difference was found at all time-points up to 2 years following RT (p < 0.004). The results of our study shows that pre-existing lymphopenia (prior to RT) is associated with a 3 times greater chance of death compared to patients with normal lymphocyte levels prior to RT. The PFS significantly affected by lymphopenia at all time-points after RT. An NLR of more than 4 was associated with a 3-time higher risk of recurrence than lower NLR scores (p = 0.0054). CONCLUSION: Our results support the relevance of lymphopenia and NLR in the prognosis of rectal cancer. We believe this is the first study showing a negative correlation between sustained lymphopenia and OS following RT.

Automated thermal imaging monitors the local response to cervical cancer brachytherapy.

Malignant tumors have high metabolic and perfusion rates, which result in a unique temperature distribution as compared to healthy tissues. Here, we sought to characterize the thermal response of the cervix following brachytherapy in women with advanced cervical carcinoma. Six patients underwent imaging with a thermal camera before a brachytherapy treatment session and after a 7-day follow-up period. A designated algorithm was used to calculate and store the texture parameters of the examined tissues across all time points. We used supervised machine learning classification methods (K Nearest Neighbors and Support Vector Machine) and unsupervised machine learning classification (K-means). Our algorithms demonstrated a 100% detection rate for physiological changes in cervical tumors before and after brachytherapy. Thus, we showed that thermal imaging combined with advanced feature extraction could potentially be used to detect tissue-specific changes in the cervix in response to local brachytherapy for cervical cancer.

[Ectopic pregnancy as a presenting symptom for lung cancer].

This article describes a rare presentation of squamous cell carcinoma of the lung, mimicking an ectopic pregnancy secreting beta-hCG protein in a 47 year old female smoker, who was treated with Methotrexate and subsequently curettage, tubectomy and right ovariectomy, because of suspected hydatidiform mole. This document presents a rare and chaotic case of lung cancer and reviews the differential diagnosis of an increased level of the beta-hCG marker and the therapeutic approach to these cases.

Palliative radiation therapy for symptomatic advance breast cancer.

In this study, we evaluated the effectiveness of palliative breast radiation therapy (RT), with single fraction RT compared with fractionated RT. Our study showed that both RT fractionation schemas provide palliation. Single fraction RT allowed for treatment with minimal interference with systemic therapy, whereas fractionated RT provided a more durable palliative response. Due to equivalent palliative response, at our institution we have increasingly been providing single fraction RT palliation during the COVID-19 pandemic.

Thermal Monitoring of Tumor and Tissue State during Radiation Therapy - A Complex Case of Radiation Recall.

Common radiation dermatitis over radiation fields can be mild as minor erythema but can also be associated with blisters and skin desquamation. This phenomenon has been widely investigated and documented, especially in breast cancer patients. Obesity, smoking, and diabetes are known risk factors; however, we cannot predict the severity of radiation dermatitis prior to treatment. The overwhelming radiation recall dermatitis is an acute inflammatory reaction confined to previously irradiated areas that can be triggered when chemotherapy agents are administered after radiotherapy. This rare, painful skin reaction leads to treatment cessation or alteration. In this study, we investigate the feasibility of using thermography as a tool to predict the response of normal breast tissue and skin to radiation therapy and the risk of developing radiation recall dermatitis. Six women with viable in-breast tumor (breast cancer) and eight women who underwent tumor resection (lumpectomy) were monitored by a thermal camera prior to radiotherapy treatment (breast region) and on weekly basis, in the same environmental conditions, through the radiation course of treatment. One patient developed radiation recall dermatitis when treated with chemotherapy following radiation therapy, and needed intensive local treatments and narcotics with full recovery thereafter. Clinical and treatment data as well as response to radiation were collected prospectively. The ongoing thermal changes observed during the radiation treatment for all patients, with and without viable tumor in the breast, were documented, analyzed, and reported here with detailed comparison to the recognized data for the patient diagnosed with radiation recall dermatitis.

Pain palliation in patients with bone metastases using MR-guided focused ultrasound surgery: a multicenter study.

BACKGROUND: Noninvasive thermal ablation using magnetic resonance (MR)-guided focused ultrasound (MRgFUS) has been shown to be clinically effective in uterine fibroids, and is being evaluated for ablation of breast, liver, and brain lesions. Recently MRgFUS has been evaluated for palliation of pain caused by bone metastases. We present the clinical results of a multicenter study using MRgFUS for palliation of bone metastases pain. METHODS: A multicenter study to evaluate the safety and efficacy of MRgFUS palliative treatment of bone metastases was conducted in patients suffering from painful metastatic bone lesions for which other treatments were either ineffective or not feasible. Thirty-one patients with painful bone metastases underwent the MRgFUS procedure in three medical centers. Treatment safety was evaluated by assessing the device-related complications. Effectiveness of pain palliation was evaluated using the visual analog pain score (VAS), and measurable changes in the intake of opioid analgesics. RESULTS: Thirty-six procedures were performed on 31 patients. Mean follow-up time was 4 months. 25 patients underwent the planned treatment and were available for 3 months post-treatment follow-up. 72% of the patients (18/25) reported significant pain improvement. Average VAS score was reduced from 5.9 prior to treatment to 1.8 at 3 months post treatment. 67% of patients with recorded medication data reported a reduction in their opioid usage. No device-related severe adverse events were recorded. CONCLUSION: The results suggest that MRgFUS has the ability to provide an accurate, effective, and safe noninvasive palliative treatment for patients with bone metastases.

Continuous Positive Airway Pressure for Motion Management in Stereotactic Body Radiation Therapy to the Lung: A Controlled Pilot Study.

OBJECTIVE: To determine the effect of continuous positive airway pressure (CPAP) on tumor motion, lung volume, and dose to critical organs in patients receiving stereotactic body radiation therapy (SBRT) for lung tumors. METHODS AND MATERIALS: After institutional review board approval in December 2013, patients with primary or secondary lung tumors referred for SBRT underwent 4-dimensional computed tomographic simulation twice: with free breathing and with CPAP. Tumor excursion was calculated by subtracting the vector of the greatest dimension of the gross tumor volume (GTV) from the internal target volume (ITV). Volumetric and dosimetric determinations were compared with the Wilcoxon signed-rank test. CPAP was used during treatment if judged beneficial. RESULTS: CPAP was tolerated well in 10 of the 11 patients enrolled. Ten patients with 18 lesions were evaluated. The use of CPAP decreased tumor excursion by 0.5 ± 0.8 cm, 0.4 ± 0.7 cm, and 0.6 ± 0.8 cm in the superior-inferior, right-left, and anterior-posterior planes, respectively (P ≤ .02). Relative to free breathing, the mean ITV reduction was 27% (95% confidence interval [CI] 16%-39%, P<.001). CPAP significantly augmented lung volume, with a mean absolute increase of 915 ± 432 cm(3) and a relative increase of 32% (95% CI 21%-42%, P=.003), contributing to a 22% relative reduction (95% CI 13%-32%, P=.001) in mean lung dose. The use of CPAP was also associated with a relative reduction in mean heart dose by 29% (95% CI 23%-36%, P=.001). CONCLUSION: In this pilot study, CPAP significantly reduced lung tumor motion compared with free breathing. The smaller ITV, the planning target volume (PTV), and the increase in total lung volume associated with CPAP contributed to a reduction in lung and heart dose. CPAP was well tolerated, reproducible, and simple to implement in the treatment room and should be evaluated further as a novel strategy for motion management in radiation therapy.

Orbital lymphoma: is it necessary to treat the entire orbit?

PURPOSE: Conformal radiotherapy (RT) has been used for all patients with orbital lymphoma treated at our institution since 1997. We retrospectively reviewed the charts of 23 consecutive patients to test the hypothesis that partial orbit RT is effective and less toxic than whole orbit RT. METHODS AND MATERIALS: Twelve patients with limited lesions were treated to partial orbital volumes and 11 patients (1 with bilateral disease) with more extensive lesions received whole orbit RT. The dose was 20-30 Gy (median, 25.2 Gy) for 19 patients with low-grade lymphoma and 24-40 Gy (median, 39.6 Gy) for 5 patients with intermediate- to high-grade lymphoma. The follow-up was 12-68 months (median, 34 months). RESULTS: All patients had a complete response to RT. Intraorbital recurrence developed in previously uninvolved areas not included in the initial target volume in 4 patients (33%) treated with partial orbit RT. All were salvaged by repeat RT or surgery. No patient treated with whole orbit RT developed intraorbital recurrence. The acute and long-term toxicity was similar in both groups. All but 1 patient retained good vision. CONCLUSION: Patients with orbital lymphoma should be treated to the entire orbit. An effective dose of RT for low-grade lesions is 25 Gy, which results in minimal morbidity even when delivered to the entire orbit.

Inhibition of P-TEFb by DRB suppresses SIRT1/CK2α pathway and enhances radiosensitivity of human cancer cells.

BACKGROUND: Positive transcription elongation factor-b (P-TEFb) is a complex containing CDK9 and a cyclin (T1, T2 or K). The effect of inhibition of P-TEFb by 5,6-dichloro-l-ß-D-ribofuranosyl benzimidazole (DRB) on cell radiosensitivity and the underlying mechanisms were investigated. MATERIALS AND METHODS: Six human cancer cell lines were subjected to (3)H-uridine incorporation, cell viability and clonogenic cell survival assays; cell-cycle redistribution and apoptosis assay; western blots and nuclear 53BP1 foci analysis after exposing the cells to DRB with/without γ-radiation. RESULTS: DRB suppressed colony formation and enhanced radiosensitivity of all cell lines. DRB caused a further increase in radiation-induced apoptosis and cell-cycle redistribution depending on p53 status. DRB prolonged the presence of radiation-induced nuclear p53 binding protein-1 (53BP1) foci and suppressed the expression of sirtuin-1 (SIRT1) and casein kinase 2-alpha (CK2α), suggesting an inhibition of DNA repair processes. CONCLUSION: Our findings indicate that DRB has the potential to increase the efficacy of radiotherapy and warrants further investigation using in vivo tumor models.