Understanding the impact of the COVID-19 pandemic on systemic anticancer therapy delivery (SACT) is crucial to appreciate the short- and long-term consequences for cancer patients and plan future ...care. Here, we report real-time national SACT delivery data from NHS Scotland. We demonstrate an initial rapid reduction in patient attendance of 28.7% with subsequent rapid recovery following service redesign. The smallest decrease was seen in breast cancer (19.7%), which also had the most rapid recovery and the largest decrease seen in colorectal cancer (43.4%). Regional variation in the magnitude of impact on SACT delivery was observed, but nadirs occurred at the same time and the rate of recovery was similar across all regions. This recovery reflected a coordinated national approach and associated patient and clinician support structures, which facilitated the creation of COVID-19-protected areas for SACT delivery in Scottish cancer centres enabling rapid sharing of successful and innovative strategies. The data show that these actions have limited the disadvantage to cancer patients.
Background Cervical cancer is the fourth most common cancer in women, with an estimated 342,000 deaths worldwide in 2020. Current standard of care in the UK for locally advanced cervical cancer is ...concurrent chemoradiotherapy with weekly cisplatin, yet 5-year overall survival rates are only 65% with a distant relapse rate of 50%. Inhibitors of Apoptosis Proteins (IAPs) are often overexpressed in cancer cells and associated with tumour progression and resistance to treatment. Tolinapant, developed by Astex Pharmaceuticals, is an IAP antagonist with an additional mechanism of action via down-regulation of NF-kB, an important regulator in cervical cancer. Preclinical studies performed using tolinapant in combination with cisplatin and radiotherapy showed inhibition of tumour growth and enhanced survival. There is therefore a strong rationale to combine tolinapant with chemoradiotherapy (CRT). Methods CRAIN is a phase Ib open-label, dose escalation study to characterise the safety, tolerability and initial evidence for clinical activity of tolinapant when administered in combination with cisplatin based CRT. Up to 42 patients with newly diagnosed cervix cancer will be recruited from six UK secondary care sites. The number of participants and the duration of the trial will depend on toxicities observed and dose escalation decisions, utilising a TiTE-CRM statistical design. Treatment will constist of standard of care CRT with 45 Gy external beam radiotherapy given in 25 daily fractions over 5 weeks with weekly cisplatin 40mg/m.sup.2. This is followed by brachytherapy for which common schedules will be 28 Gy in 4 fractions high-dose-rate or 34 Gy in 2 fractions pulsed-dose-rate. Tolinapant will be administered in fixed dose capsules taken orally daily for seven consecutive days as an outpatient on alternate weeks (weeks 1, 3, 5) during chemoradiation. Dose levels for tolinapant which will be assessed are: 60 mg; 90 mg (starting level); 120 mg; 150 mg; 180 mg. Escalation will be guided by emerging safety data and decisions by the Safety Review Committee. Discussion If this trial determines a recommended phase II dose and shows tolinapant to be safe and effective in combination with CRT, it would warrant future phase trials. Ultimately, we hope to provide a synergistic treatment option for these patients to improve outcome. Trial registrations EudraCT Number: 2021-006555-34 (issued 30th November 2021); ISRCTN18574865 (registered 30th August 2022). Keywords: Cervical cancer, Tolinapant, Chemoradiotherapy, Cisplatin, Phase I
Purpose of Review
To evaluate the evidence for the use of fluorine-18-fluorodeoyglucose (18F-FDG) PET CT in external beam radiotherapy planning for treatment of gynaecological malignancies.
Recent ...Findings
Our review confirms that the incorporation of 18F-FDG PET CT during radiotherapy planning may decrease inter-observer variability during target delineation. It can also provide useful functional information regarding the tumour, which may facilitate the development of techniques for dose escalation and ‘dose painting’ not only for primary disease, especially in cervical cancer, but also nodal metastasis.
Summary
The utilisation of this functional modality in external beam radiotherapy planning, particularly in locally advanced cervical malignancy, is an exciting topic that warrants further prospective research. Perhaps the most valuable role may be the potential to deliver dose escalation to 18F-FDG PET CT avid targets previously limited by organ at risk constraints, now that we have significantly more advanced radiotherapy planning tools at our disposal.
Management of early endometrial cancer is contentious these days with little agreement between oncologists as well as across MDTs or tumour boards and indeed across countries. This is because of the ...state of knowledge with regards to risk factors in early endometrial cancer; although we recognise risk factors affect outcome, we haven’t yet been able to demonstrate that our treatments make a significant difference. We have reviewed available literature on LVSI and are able to demonstrate that it is an independent risk factor for nodal metastasis as well as distant recurrence. We need a randomised trial integrating grade and LVSI and testing therapeutic options of radiotherapy and chemotherapy. However, it is unlikely to see the light of day. Therefore, we are left with this knowledge of prognostic factors and it is our duty to integrate this into our decision-making during our multidisciplinary team meetings and make decisions tailored to individual patient circumstances.
Brachytherapy is an essential part of radiotherapy treatment for cervical cancer. Over the decades, it has evolved from manual loading of radium and caesium to remote after-loaders and from low-dose ...and medium-dose rates to high-dose rates. Over the past 10 years, 3D image-based Brachytherapy has evolved and established itself as the gold standard, improving local control and overall survival, and significantly reducing toxicity. In this article, we review some of the available literature on gynaecologic brachytherapy, more specifically on topics such as dose rates, high-dose-rate/pulsed-dose-rate (HDR/PDR) brachytherapy and image-based brachytherapy (IBBT), and present some of the evidence that establishes IBBT
Update on radiotherapy in gynaecological malignancies Reed, Nicholas S; Sadozye, Azmat H
Obstetrician & gynaecologist/The obstetrician & gynaecologist,
January 2017, 2017-01-00, 20170101, Volume:
19, Issue:
1
Journal Article
Peer reviewed
Open access
Key content
This article reviews the changing role of adjuvant radiation therapy in gynaecological cancer, with emphasis on data from recent clinical trials.
The evolution of practice with modern ...technology is improving the delivery of radiation, which has the potential to escalate doses, reduce toxicity and improve outcome.
Radiation is infrequently used in ovarian cancer but in selected patients may provide good palliation.
Late toxicity and survivorship issues are now recognised as important factors and there is a need to modify treatments to improve this.
Learning objectives
To learn and understand the changing uses of adjuvant radiation therapy in gynaecological cancer.
To understand the changing practice of brachytherapy, especially with the use of imaging to allow adaptive therapy.
To understand the use of high technology to improve the delivery of radiation therapy in gynaecological cancers with potential for dose escalation with improved outcome and reduced toxicities.
To understand the developments in brachytherapy and the use of computerised technologies and adaptive treatments.
Update on chemotherapy in gynaecological cancers Reed, Nicholas S; Sadozye, Azmat H
Obstetrician & gynaecologist/The obstetrician & gynaecologist,
July 2016, 2016-07-00, 20160701, Volume:
18, Issue:
3
Journal Article
Peer reviewed
Open access
Key content
Ovarian cancer requires multidisciplinary management, usually with postoperative adjuvant chemotherapy. In some cases, however, neo‐adjuvant chemotherapy and delayed surgery may be ...offered.
Recurrent ovarian cancer management is usually treated with chemotherapy, with drug choice often influenced by the platinum‐free interval.
The role of adjuvant chemotherapy for endometrial cancer remains open to debate. Adjuvant chemotherapy is increasingly offered for high‐risk cases with lymphovascular space invasion. Carboplatin and paclitaxel are the most effective drugs in adjuvant and recurrent settings.
Concomitant cisplatin with radiation therapy is the standard of care for locally advanced cervical cancer; recent studies have shown that the addition of bevacizumab to carboplatin and paclitaxel leads to improved response rates in the recurrent, metastatic setting.
There are many rare gynaecological cancers that require multidisciplinary management, and entry into clinical trials should be strongly supported.
Learning objectives
To understand the role and scheduling of chemotherapy in both newly diagnosed and recurrent epithelial ovarian cancer.
To understand when chemotherapy should be offered in cervical and endometrial cancers.
To be able to seek information sources for the management of rare and uncommon gynaecological cancers.
Ethical issues
The question of systemic lymphadenectomy remains controversial and should be carefully discussed with the patient.
Women should be encouraged to participate in clinical trials to help address some of the controversies in endometrial cancer management.
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