Resistance gene expression determines the in vitro chemosensitivity of non-small cell lung cancer (NSCLC)

Background NSCLC exhibits considerable heterogeneity in its sensitivity to chemotherapy and similar heterogeneity is noted in vitro in a variety of model systems. This study has tested the hypothesis that the molecular basis of the observed in vitro chemosensitivity of NSCLC lies within the known resistance mechanisms inherent to these patients' tumors. Methods The chemosensitivity of a series of 49 NSCLC tumors was assessed using the ATP-based tumor chemosensitivity assay (ATP-TCA) and compared with quantitative expression of resistance genes measured by RT-PCR in a Taqman Array™ following extraction of RNA from formalin-fixed paraffin-embedded (FFPE) tissue. Results There was considerable heterogeneity between tumors within the ATP-TCA, and while this showed no direct correlation with individual gene expression, there was strong correlation of multi-gene signatures for many of the single agents and combinations tested. For instance, docetaxel activity showed some dependence on the expression of drug pumps, while cisplatin activity showed some dependence on DNA repair enzyme expression. Activity of both drugs was influenced more strongly still by the expression of anti- and pro-apoptotic genes by the tumor for both docetaxel and cisplatin. The doublet combinations of cisplatin with gemcitabine and cisplatin with docetaxel showed gene expression signatures incorporating resistance mechanisms for both agents. Conclusion Genes predicted to be involved in known mechanisms drug sensitivity and resistance correlate well with in vitro chemosensitivity and may allow the definition of predictive signatures to guide individualized chemotherapy in lung cancer

Therapies in Cervical Cancer—Editorial

George Papanikolaou is famously quoted as saying “the first observation of cancer cells in the smear of the uterine cervix gave me one of the greatest thrills I ever experienced during my scientific career” [...

A single centre evaluation of the 2019 UK SABR consortium guidelines for primary lung cancer: correlation between Prescription Dose Spillage and inverse Paddick Conformity Index

Background: The aim of the study was to determine level of agreement between RTOG Conformity Index (RTOG-CI), Paddick Conformity Index (PCI) and Prescription Dose Spillage (PDS) in describing lung stereotactic ablative radiotherapy (SABR) plan conformity; to elucidate any limitations, in practice, of PCI and PDS. International Commission on Radiation Units and Measurements report 91 (ICRU 91) aimed to reduce inconsistencies in dose prescription and normalisation between centres by specifying SABR reporting rules, and suggested using PCI. UK SABR Consortium 2019 guidelines adopted PDS to measure plan quality, but not the PCI. Materials and methods: 51 consecutive lung SABR plans received 54 Gy in 3 fractions (54 Gy/3 Fr), 55 Gy/5 Fr or 60 Gy/8 Fr. Plans were developed according to 2016 UK SABR consortium guidelines, which did not specify PCI or PDS; these values were retrospectively calculated. As PCI varies from 0 to an optimum of 1, inverse PCI (invPCI) was used for calculations. Results: PTV-adjusted PDS tolerances were met in 80.4% of studied plans. A near-perfect positive correlation between invPCI and PDS (R2 = 0.978) was found — stronger than between invPCI and the previously-used RTOG-CI (R2 = 0.915). Conclusions: The strong invPCI-PDS correlation is likely dependent on adequate PTV coverage, present in our cohort. This supports the UK SABR Consortium’s adoption of PDS provided PTV coverage is ensured. Plan conformity should be confirmed by visual slice-by-slice review

A single centre evaluation of the 2019 UK SABR consortium guidelines for primary lung cancer: correlation between Prescription Dose Spillage and inverse Paddick Conformity Index

BackgroundThe aim of the study was to determine level of agreement between RTOG Conformity Index (RTOG-CI), Paddick Conformity Index (PCI) and Prescription Dose Spillage (PDS) in describing lung stereotactic ablative radiotherapy (SABR) plan conformity; to elucidate any limitations, in practice, of PCI and PDS. International Commission on Radiation Units and Measurements report 91 (ICRU 91) aimed to reduce inconsistencies in dose prescription and normalisation between centres by specifying SABR reporting rules, and suggested using PCI. UK SABR Consortium 2019 guidelines adopted PDS to measure plan quality, but not the PCI.Materials and methods51 consecutive lung SABR plans received 54 Gy in 3 fractions (54 Gy/3 Fr), 55 Gy/5 Fr or 60 Gy/8 Fr. Plans were developed according to 2016 UK SABR consortium guidelines, which did not specify PCI or PDS; these values were retrospectively calculated. As PCI varies from 0 to an optimum of 1, inverse PCI (invPCI) was used for calculations.ResultsPTV-adjusted PDS tolerances were met in 80.4% of studied plans. A near-perfect positive correlation between invPCI and PDS (R2 = 0.978) was found - stronger than between invPCI and the previously-used RTOG-CI (R2 = 0.915).ConclusionsThe strong invPCI-PDS correlation is likely dependent on adequate PTV coverage, present in our cohort. This supports the UK SABR Consortium's adoption of PDS provided PTV coverage is ensured. Plan conformity should be confirmed by visual slice-by-slice review

Unilateral Optic Disc Papilloedema following Administration of Carboplatin Chemotherapy for Ovarian Carcinoma

A 48-year-old woman with a positive BRCA1 gene mutation was diagnosed with stage 3b high-grade ovarian endometrioid carcinoma. She was treated with adjuvant carboplatin at a dose of 740 mg (AUC 6) in 3-weekly cycles. Five days after her fifth cycle of carboplatin, she awoke with new-onset blurred vision in her left eye. An ophthalmology review showed left-sided disc oedema with normal optic nerve function tests and 6/24 visual acuity. A CT scan of the head and orbits was performed which showed no evidence of metastasis or raised intracranial pressure. An autoimmune screen was performed which did not reveal any explanation for her visual symptoms. Fundus fluorescein angiography showed bilateral intense late disc leakage with no evidence of vasculitis. Her chemotherapy was stopped in view of a radiological and biochemical remission and her visual symptoms were monitored. She was also started on a tapering dose of prednisolone 40 mg daily. Five months after the initial review, she has developed left optic disc atrophy with 6/18 visual acuity, while the right eye remains asymptomatic. The diagnosis was felt to be that of carboplatin-induced unilateral disc oedema, a very rare side effect of this chemotherapy

British Gynaecological Cancer Society recommendations for women with gynecological cancer who received non-standard care during the COVID-19 pandemic.

During the COVID-19 pandemic, pressures on clinical services required adaptation to how care was prioritised and delivered for women with gynecological cancer. This document discusses potential 'salvage' measures when treatment has deviated from the usual standard of care. The British Gynaecological Cancer Society convened a multidisciplinary working group to develop recommendations for the onward management and follow-up of women with gynecological cancer who have been impacted by a change in treatment during the pandemic. These recommendations are presented for each tumor type and for healthcare systems, and the impact on gynecological services are discussed. It will be important that patient concerns about the impact of COVID-19 on their cancer pathway are acknowledged and addressed for their ongoing care