Impact of the COVID-19 Pandemic on Outcomes for Patients with Lung Cancer Receiving Curative-intent Radiotherapy in the UK.

AIMS: Previous work found that during the first wave of the COVID-19 pandemic, 34% of patients with lung cancer treated with curative-intent radiotherapy in the UK had a change to their centre's usual standard of care treatment (Banfill et al. Clin Oncol 2022;34:19-27). We present the impact of these changes on patient outcomes. MATERIALS AND METHODS: The COVID-RT Lung database was a prospective multicentre UK cohort study including patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between April and October 2020. Data were collected on patient demographics, radiotherapy and systemic treatments, toxicity, relapse and death. Multivariable Cox and logistic regression were used to assess the impact of having a change to radiotherapy on survival, distant relapse and grade ≥3 acute toxicity. The impact of omitting chemotherapy on survival and relapse was assessed using multivariable Cox regression. RESULTS: Patient and follow-up forms were available for 1280 patients. Seven hundred and sixty-five (59.8%) patients were aged over 70 years and 603 (47.1%) were female. The median follow-up was 213 days (119, 376). Patients with stage I-II non-small cell lung cancer (NSCLC) who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.859) or death (P = 0.884); however, they did have increased odds of grade ≥3 acute toxicity (P = 0.0348). Patients with stage III NSCLC who had a change to their radiotherapy had no significant increase in distant relapse (P = 0.216) or death (P = 0.789); however, they did have increased odds of grade ≥3 acute toxicity (P < 0.001). Patients with stage III NSCLC who had their chemotherapy omitted had no significant increase in distant relapse (P = 0.0827) or death (P = 0.0661). CONCLUSION: This study suggests that changes to radiotherapy and chemotherapy made in response to the COVID-19 pandemic did not significantly affect distant relapse or survival. Changes to radiotherapy, namely increased hypofractionation, led to increased odds of grade ≥3 acute toxicity. These results are important, as hypofractionated treatments can help to reduce hospital attendances in the context of potential future emergency situations.

Intensive care management in guillain barré syndrome accompanying prolonged Covid-19-A case report.

One of the neurological complications associated with COVID-19 is Guillain Barre Syndrome (GBS). It is possible to be a complication of COVID19 due to the similarity of respiratory complication between both clinical entities. The aim of this case report is to present a case followed in the intensive care unit (ICU) with the coexistence of prolonged COVID-19 and GBS. The 68-year-old patient, whose COVID-19 symptoms had been going on for 5 weeks, was followed for 5 days in the ICU due to GBS diagnosis. During this period, the patient's symptoms regressed with IVIG treatment. ICU physicians should be careful that some neurological complications may accompany in some prolonged COVID-19 cases and that one of these may be GBS.

Changes in the Management of Patients having Radical Radiotherapy for Lung Cancer during the First Wave of the COVID-19 Pandemic in the UK.

AIMS: In response to the COVID-19 pandemic, guidelines on reduced fractionation for patients treated with curative-intent radiotherapy were published, aimed at reducing the number of hospital attendances and potential exposure of vulnerable patients to minimise the risk of COVID-19 infection. We describe the changes that took place in the management of patients with stage I-III lung cancer from April to October 2020. MATERIALS AND METHODS: Lung Radiotherapy during the COVID-19 Pandemic (COVID-RT Lung) is a prospective multicentre UK cohort study. The inclusion criteria were: patients with stage I-III lung cancer referred for and/or treated with radical radiotherapy between 2nd April and 2nd October 2020. Patients who had had a change in their management and those who continued with standard management were included. Data on demographics, COVID-19 diagnosis, diagnostic work-up, radiotherapy and systemic treatment were collected and reported as counts and percentages. Patient characteristics associated with a change in treatment were analysed using multivariable binary logistic regression. RESULTS: In total, 1553 patients were included (median age 72 years, 49% female); 93 (12%) had a change to their diagnostic investigation and 528 (34%) had a change to their treatment from their centre's standard of care as a result of the COVID-19 pandemic. Age ≥70 years, male gender and stage III disease were associated with a change in treatment on multivariable analysis. Patients who had their treatment changed had a median of 15 fractions of radiotherapy compared with a median of 20 fractions in those who did not have their treatment changed. Low rates of COVID-19 infection were seen during or after radiotherapy, with only 21 patients (1.4%) developing the disease. CONCLUSIONS: The COVID-19 pandemic resulted in changes to patient treatment in line with national recommendations. The main change was an increase in hypofractionation. Further work is ongoing to analyse the impact of these changes on patient outcomes.

Reduced Fractionation in Lung Cancer Patients Treated with Curative-intent Radiotherapy during the COVID-19 Pandemic.

Patients treated with curative-intent lung radiotherapy are in the group at highest risk of severe complications and death from COVID-19. There is therefore an urgent need to reduce the risks associated with multiple hospital visits and their anti-cancer treatment. One recommendation is to consider alternative dose-fractionation schedules or radiotherapy techniques. This would also increase radiotherapy service capacity for operable patients with stage I-III lung cancer, who might be unable to have surgery during the pandemic. Here we identify reduced-fractionation for curative-intent radiotherapy regimes in lung cancer, from a literature search carried out between 20/03/2020 and 30/03/2020 as well as published and unpublished audits of hypofractionated regimes from UK centres. Evidence, practical considerations and limitations are discussed for early-stage NSCLC, stage III NSCLC, early-stage and locally advanced SCLC. We recommend discussion of this guidance document with other specialist lung MDT members to disseminate the potential changes to radiotherapy practices that could be made to reduce pressure on other departments such as thoracic surgery. It is also a crucial part of the consent process to ensure that the risks and benefits of undergoing cancer treatment during the COVID-19 pandemic and the uncertainties surrounding toxicity from reduced fractionation have been adequately discussed with patients. Furthermore, centres should document all deviations from standard protocols, and we urge all colleagues, where possible, to join national/international data collection initiatives (such as COVID-RT Lung) aimed at recording the impact of the COVID-19 pandemic on lung cancer treatment and outcomes.

Continuous Hyperfractionated Accelerated Radiotherapy (CHART) for Non-small Cell Lung Cancer (NSCLC): 7 Years' Experience From Nine UK Centres.

AIM: Continuous hyperfractionated accelerated radiotherapy (CHART) remains an option to treat non-small cell lung cancer (NSCLC; NICE, 2011). We have previously published treatment outcomes from 1998-2003 across five UK centres. Here we update the UK CHART experience, reporting outcomes and toxicities for patients treated between 2003 and 2009. MATERIALS AND METHODS: UK CHART centres were invited to participate in a retrospective data analysis of NSCLC patients treated with CHART from 2003 to 2009. Nine (of 14) centres were able to submit their data into a standard database. The Kaplan-Meier method estimated survival and the Log-rank test analysed the significance. RESULTS: In total, 849 patients had CHART treatment, with a median age of 71 years (range 31-91), 534 (63%) were men, 55% had undergone positron emission tomography-computed tomography (PET-CT) and 26% had prior chemotherapy; 839 (99%) patients received all the prescribed treatment. The median overall survival was 22 months with 2 and 3 year survival of 47% and 32%, respectively. Statistically significant differences in survival were noted for stage IA versus IB (33.2 months versus 25 months; P = 0.032) and IIIA versus IIIB (20 months versus 16 months; P = 0.018). Response at 3 months and outcomes were significantly linked; complete response showing survival of 34 months against 19 months, 15 months and 8 months for partial response, stable and progressive disease, respectively (P < 0.001). Age, gender, performance status, prior chemotherapy and PET-CT did not affect the survival outcomes. Treatment was well tolerated with <5% reporting ≥grade 3 toxicity. CONCLUSION: In routine practice, CHART results for NSCLC remain encouraging and we have been able to show an improvement in survival compared with the original trial cohort. We have confirmed that CHART remains deliverable with low toxicity rates and we are taking a dose-escalated CHART regimen forward in a randomised phase II study of sequential chemoradiotherapy against other accelerated dose-escalated schedules.

Stage IA vs. IB endometrial stromal sarcoma: does the new staging system predict survival?

OBJECTIVE: To determine the correlation of the new FIGO staging system with survival in stage I patients with low-grade and high-grade endometrial stromal sarcomas. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Kaplan-Meier log rank and Cox proportional hazards models were used for survival analysis and to identify possible predictors for survival. RESULTS: The identified cohort included 464 women, 310 (67%) low-grade endometrial stromal sarcoma, 96 (21%) high-grade endometrial stromal sarcoma, and 58 (12%) unclassified endometrial stromal sarcoma. Among low-grade and high-grade endometrial stromal sarcomas, there was no significant demographic or clinico-pathologic difference between stages IA and IB. The 5-year overall survival was worse in high-grade endometrial stromal sarcoma than low-grade endometrial stromal sarcoma (45.4% vs. 97.2%, p<0.001). The difference in 5-year overall survival among women with low-grade endometrial stromal sarcoma between stages IA and IB was significant (100% vs. 93.5%, p=0.003), but not among women with high-grade endometrial stromal sarcoma (51.4% vs. 43.5%, p=0.27). Although age (p=0.001), race (p=0.005), and stage (p=0.004) were all significant prognostic factors in low-grade endometrial stromal sarcoma, only cervical involvement (p=0.02) was a significant predictor in high-grade endometrial stromal sarcoma. CONCLUSION: The new staging system is appropriate for risk stratification in low-grade endometrial stromal sarcoma. The prognosis in high-grade endometrial stromal sarcoma seems to be most influenced by the presence of cervical involvement and not by tumor size as the staging criteria would suggest.

Adiaspiromycosis mimicking widespread malignancy in a patient with pulmonary adenocarcinoma.

Adiaspiromycosis, a mycotic disease of small animals, has rarely been reported in humans. The principle causative organism in Europe is Emmonsia crescens. Inhaled, dust-borne spores of E crescens fail to germinate in host tissue, instead increasing in size dramatically to become thick-walled, round adiapsores, which induce a granulomatous response. The pathological effects depend on the spore burden and host immunocompetence, and range from asymptomatic infection through to necrogranulomatous pneumonia, respiratory failure and, rarely, death. Diagnosis is principally made through histological examination. This report describes a case of a patient with low-grade, localised pulmonary adenocarcinoma with occult adiaspiromycosis that radiologically mimicked widespread malignancy. It is believed to be the first reported human case of adiaspiromycosis in the UK.

Palliative radiotherapy regimens for non-small cell lung cancer.

BACKGROUND: Palliative radiotherapy to the chest is often used in patients with lung cancer, but radiotherapy regimens are more often based on tradition than research results. OBJECTIVES: To discover the most effective and least toxic regimens of palliative radiotherapy for non-small cell lung cancer, and whether higher doses increase survival. SEARCH STRATEGY: The electronic databases MEDLINE, EMBASE, Cancerlit and the Cochrane Central Register of Controlled Trials, reference lists, handsearching of journals and conference proceedings, and discussion with experts were used to identify potentially eligible trials, published and unpublished. SELECTION CRITERIA: Randomised controlled clinical trials comparing different regimens of palliative radiotherapy in patients with non-small cell lung cancer. DATA COLLECTION AND ANALYSIS: Fourteen randomised trials were reviewed. There were important differences in the doses of radiotherapy investigated, the patient characteristics and the outcome measures. Because of this heterogeneity no meta-analysis was attempted. MAIN RESULTS: There is no strong evidence that any regimen gives greater palliation. Higher dose regimens give more acute toxicity, especially oesophagitis. There is evidence for a modest increase in survival (5% at 1 year and 3% at 2 years) in patients with better performance status (PS) given higher dose radiotherapy. Some regimens are associated with an increased risk of radiation myelitis. AUTHORS' CONCLUSIONS: The majority of patients should be treated with short courses of palliative radiotherapy, of 1 or 2 fractions. Care should be taken with the dose to the spinal cord. The use of high dose palliative regimens should be considered for and discussed with selected patients with good performance status. More research is needed into reducing the acute toxicity of large fraction regimens and into the role of radical compared to high dose palliative radiotherapy. In the future, large trials comparing different RT regimens may be difficult to set up because of the increasing use of systemic chemotherapy. Trials looking at how best to integrate these two modalities, particularly in good PS patients, need to be carried out.

Block sequential adriamycin CMF--optimal non-myeloablative chemotherapy for high risk adjuvant breast cancer?

After the publication of the 10-year survival data from Milan on the adjuvant use of the block sequential regimen consisting of four cycles of adriamycin followed by eight cycles of intravenous CMF, many centres adopted this as standard of care for high risk, multiple node-positive breast cancer. For this reason it was identified as the standard arm for the Anglo-Celtic adjuvant high-dose chemotherapy trial. This study reports on the experience of this regimen in 329 women with early breast cancer involving at least four axillary nodes, who were treated outside any adjuvant chemotherapy trial. At a median follow-up of 3 years, the overall 5-year disease-free survival is 61%, and the overall survival is 70%. These data confirm the efficacy of this regimen in non-trial patients, and, for the same high risk subgroup, indicate that this approach offers an outcome at least as good as that seen in the CALGB 9344 AC-Taxol arm, and the NCIC days 1 and 8 CEF.

Palliative radiotherapy regimens for non-small cell lung cancer.

BACKGROUND: Palliative radiotherapy (RT) to the chest is often used in patients with lung cancer, but RT regimens are more often based on tradition than research results. OBJECTIVES: To discover the most effective and least toxic regimens of palliative RT, and whether higher doses increase survival. SEARCH STRATEGY: Electronic databases, reference lists, handsearching of journals and conference proceedings, and discussion with experts were used to identify potentially eligible trials, published and unpublished. SELECTION CRITERIA: Randomised controlled clinical trials comparing different regimens of palliative RT in patients with non-small lung cancer. DATA COLLECTION AND ANALYSIS: Ten randomised trials were reviewed. There were important differences in the doses of RT investigated, the patient characteristics and the outcome measures. Because of this heterogeneity no meta-analysis was attempted. MAIN RESULTS: There is no strong evidence that any regimen gives greater palliation. Higher dose regimens give more acute toxicity. There is evidence for a modest increase in survival (6% at 1 year and 3% at 2 years) in patients with better performance status (PS) given higher dose RT. REVIEWER'S CONCLUSIONS: The majority of patients should be treated with short courses of palliative RT, of 1 or 2 fractions. Care should be taken with the dose to the spinal cord. The use of high dose palliative regimens should be considered for and discussed with selected patients with good PS. More research is needed into reducing the acute toxicity of large fraction regimens and into the role of radical compared to high dose palliative RT and more homogeneous studies are needed.

Modeling for health care and other policy decisions: uses, roles, and validity.

The role of models to support recommendations on the cost-effective use of medical technologies and pharmaceuticals is controversial. At the heart of the controversy is the degree to which experimental or other empirical evidence should be required prior to model use. The controversy stems in part from a misconception that the role of models is to establish truth rather than to guide clinical and policy decisions. In other domains of public policy that involve human life and health, such as environmental protection and defense strategy, models are generally accepted as decision aids, and many models have been formally incorporated into regulatory processes and governmental decision making. We formulate an analytical framework for evaluating the role of models as aids to decision making. Implications for the implementation of Section 114 of the Food and Drug Administration Modernization Act (FDAMA) are derived from this framework.

Early feeding after cesarean: randomized trial.

OBJECTIVE: To study the rate of ileus symptoms and hospital course of women who are offered solid food shortly after cesarean delivery. METHODS: This study involved women delivered by cesarean under regional anesthesia. Exclusion criteria included general anesthesia, magnesium sulfate, intra-operative bowel injury or bowel surgery, or other conditions that precluded early feeding. Early-fed women were offered regular diets within 8 hours of surgery, and controls were given nothing by mouth for 12-24 hours, advanced to clear liquids on the first postoperative day, and then given solid food on the second or third postoperative day. RESULTS: Sixty women were assigned randomly to each method. Early-fed women received solid food sooner after surgery, 5.0 +/- 1.2 hours versus 40.0 +/- 10.6 hours. The incidences of mild ileus symptoms and postoperative complications were similar in both groups; however, the study did not have an adequate sample size to definitively assess safety concerns. Women in the early-fed group had shorter hospital stays (49.5 +/- 12.7 hours versus 75.0 +/- 12.3 hours, P <.001), and shorter time intervals from surgery to bowel movement, 34.5 hours (interquartile range 25.3-48.8) versus 51.0 (43.3-62.0) hours, P <.001. In the early-fed group, women whose operative times exceeded 40 minutes were more likely to have symptoms of mild ileus. CONCLUSION: Early initiation of solid food after cesarean delivery appears to be well tolerated and may be associated with a shorter hospital stay. Early-fed women whose operations exceed 40 minutes may be more likely to have mild ileus symptoms.

Palliative radiotherapy regimens for non-small cell lung cancer.

BACKGROUND: Palliative radiotherapy (RT) to the chest is often used in patients with lung cancer, but RT regimens are more often based on tradition than research results. OBJECTIVES: To discover the most effective and least toxic regimens of palliative RT, and whether higher doses increase survival. SEARCH STRATEGY: Electronic databases, reference lists, handsearching of journals and conference proceedings, and discussion with experts were used to identify potentially eligible trials, published and unpublished. SELECTION CRITERIA: Randomised controlled clinical trials comparing different regimens of palliative RT in patients with non-small lung cancer. DATA COLLECTION AND ANALYSIS: Ten randomised trials were reviewed. There were important differences in the doses of RT investigated, the patient characteristics and the outcome measures. Because of this heterogeneity no meta-analysis was attempted. MAIN RESULTS: There is no strong evidence that any regimen gives greater palliation. Higher dose regimens give more acute toxicity. There is evidence for a modest increase in survival (6% at 1 year and 3% at 2 years) in patients with better performance status (PS) given higher dose RT. REVIEWER'S CONCLUSIONS: The majority of patients should be treated with short courses of palliative RT, of 1 or 2 fractions. Care should be taken with the dose to the spinal cord. The use of high dose palliative regimens should be considered for and discussed with selected patients with good PS. More research is needed into reducing the acute toxicity of large fraction regimens and into the role of radical compared to high dose palliative RT and more homogeneous studies are needed.

Enhancement of orimulsion biodegradation through the addition of natural marine carbon substrates.

Orimulsion is a bitumen-based heavy fuel that is a less expensive alternative to traditional fuel oils. However, because its density is intermediate between that of freshwater and seawater, in the event of a spill, the fuel could strand in the sediments. Previous work indicated that only 0.6-2.7% of the bitumen would degrade in long incubations of marine sediments. We added various natural carbon substrates to stimulate the degradation of bitumen by native populations of benthic bacteria. The concentration and carbon isotopic signature of the respired carbon dioxide was measured to partition the substrates that supported bacterial respiration. We found that the addition of seagrass and pinfish stimulated the degradation of bitumen by as much as 2-9-fold relative to incubations without these substrates. Biodegradation of bitumen may be enhanced by the addition of natural marine carbon substrates and may be a useful approach for bioremediation. Preadaptation of the bacteria to bitumen did not significantly enhance their ability to degrade it.

Sjogren's syndrome.

Sjogren's syndrome is a chronic progressive autoimmune disorder manifested predominately by xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). It can also affect many body systems. Up to 5% of people over the age of 60 years have primary Sjogren's syndrome, and approximately one third of patients present with extraglandular (systemic) manifestations. This disease is seen mostly in middle-aged women, with a small but significant proportion of these women developing lymphoid neoplasia. The exact etiology is still unknown. This autoimmune disorder is characterized by B-cell activation, the production of numerous auto-antibodies, and the loss of immune tolerance. Salivary gland biopsy remains the most helpful diagnostic test. Treatment is aimed at moisture replacement, which alleviates the discomfort and slows the destructive process. Because of its prevalence in older women, the obstetrician-gynecologist must be aware of the diagnostic and therapeutic approach to Sjogren's syndrome.

The activated macrophage colony-stimulating factor (CSF-1) receptor as a predictor of poor outcome in advanced epithelial ovarian carcinoma.

OBJECTIVE: We have previously shown that the macrophage colony-stimulating factor receptor (CSF-1R) and its ligand, CSF-1, together predict poor prognosis in epithelial ovarian carcinoma. The activated or phosphorylated form of CSF-1R (CSF-1Rphos) has been associated with enhanced invasive and metastatic potential. Our goal is to correlate CSF-1Rphos with known prognostic factors and to determine its role in predicting outcome in advanced ovarian cancer. METHODS: One hundred forty-two primary and forty-seven metastatic epithelial ovarian tumors from 98 patients were immunohistochemically stained using antibodies PY809 and PY723 against their respective tyrosine residues associated with local invasiveness and metastasis. chi2 analysis was used to correlate CSF-1Rphos staining and previously studied prognosticators within each group. Kaplan-Meier curves of survival were comparedusing the log-rank test with significance of P < 0.05. RESULTS: Forty-seven and nine-tenths percent (68/142) of primary tumors and forty-eight and nine-tenths percent (23/47) of metastatic tumors stained positive for PY809 and PY723, respectively. The PY809+ group was strongly associated with CSF-1R (P = 0.015) as was the PY723+ group (P = 0.025) in its respective subset. CSF-1Rphos by itself was not a predictor of survival or disease-free interval (DFI) in either the primary or metastatic group. However, when combined with CSF-1R in the metastatic group, the two together predicted worse survival (P = 0.007) and decreased DFI (P = 0.011). CONCLUSIONS: Phosphorylated tyrosine kinase receptors are detectable in a significant number of ovarian tumors. Staining strongly correlates with CSF-1R. PY723+ metastases coexpressing CSF-1R portend a highly significant decrease in survival and increased risk of recurrence which may serve to identify high-risk ovarian cancer patients.

Induction of cell-cycle arrest in cervical cancer cells by the human immunodeficiency virus type 1 viral protein R.

OBJECTIVE: To determine the ability of the human immunodeficiency virus type 1 (HIV-1) gene vpr to induce cell-cycle arrest in cervical cancer cells with or without human papillomavirus (HPV) type 16 E6 or E7 expression. METHODS: High- and low-level expression vectors for vpr (designated pVPR(HIGH) and pVPR(LOW), respectively) were used in conjunction with HPV-16 E6 or E7 vectors to transfect HPV-negative C33A cervical cancer cells. Vpr expression vectors encode a cell surface marker gene, murine Thy-1, for specific detection of transfected cells. Dual staining for the surface molecule Thy-1 and DNA content was used to determine cell-cycle profile and G2-phase arrest. RESULTS: C33A cells not expressing HPV-16 E6 showed some but not maximal G2-phase arrest when transfected with pVPR(HIGH) alone (43.2% of cells in the G2 phase). Addition of HPV-16 E6 or E6 plus E7 to pVPR(HIGH) substantially increased the percentages of cells in the G2 phase (51.3% and 53.0%, respectively). Cotransfection with pVPR(HIGH) and HPV-16 E7 did not increase significantly the percentage of cells in the G2 phase compared with pVPR(HIGH) alone (40.6% versus 43.2%). In transfections involving pVPR(LOW), a slight degree of G2-phase arrest was observed when Vpr was expressed alone (29.0% of cells in the G2 phase) or in cotransfection with HPV-16 E7 (33.2% of cells), and G2-phase arrest was augmented with the addition of HPV-16 E6 (41.7%) or E6 plus E7 (45.7%). CONCLUSION: Cervical cancer cells are susceptible to cell-cycle arrest induced by HIV-1 vpr. This effect is exacerbated by coexpression of HPV-16 E6, although E6 alone is incapable of inducing any detectable G2-phase arrest, suggesting that E6 and VPR share links in cell-cycle signaling pathways.

Influenza vaccination in pregnancy.

The objective of this paper is to determine the acceptance rate of and incidence of adverse reactions to the influenza vaccine in pregnant women, and to determine the immunized patients' attitudes toward future vaccination. A total of 448 eligible pregnant women were offered the influenza vaccine at routine prenatal visits. Vaccinated women were interviewed at their subsequent visit regarding adverse effects and attitudes toward future vaccination. Of the 448 women studied, 319 (71.2%) accepted the vaccine. There was no difference in acceptance rates between English- and Spanish-speaking women. Mild adverse reactions were experienced by 5.3%. Women who reported adverse reactions were less likely to agree to future vaccination as compared with unaffected women (64.7 vs. 94.0% p < 0.001). The influenza vaccine is readily accepted by pregnant women, and is infrequently associated with mild side effects. Women who experience side effects are less likely to accept the vaccine in the future.