Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study #Covid19RftLks

COVIDSurg Collaborative | 2021| Effect of Covid-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study | The Lancet Oncology | https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00493-9/fulltext

This international study prospectively enrolled patients with a decision for curative surgery awaiting surgery during the SARS-CoV-2 pandemic and tracked their care pathways prospectively. It included data from the 15 most common solid cancer types across all country-income settings, providing wide generalisability to global policy. The analysis allowed a direct comparison of full and moderate lockdowns to light restrictions, accounting for their dynamic nature, where different patients from the same country were exposed to different lockdown states.

Their findings indicate that during full lockdowns, one in seven patients did not receive their planned operation, all of whom had a pandemic-related reason for non-operation. This finding was robust, and consistent in sensitivity analyses. In a secondary analysis, awaiting surgery in a full lockdown for greater than 6 weeks was associated with an increased likelihood of non-operation (Source: COVIDSurg Collaborative).

Summary

Background

Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction.

Methods

This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926.

Findings

Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays.

Interpretation

Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include protected elective surgical pathways and long-term investment in surge capacity for acute care during public health emergencies to protect elective staff and services.

Funding

National Institute for Health Research Global Health Research Unit, Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, Medtronic, Sarcoma UK, The Urology Foundation, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research.

Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an interrnational, prospective, cohort study [primary paper]

NIHR: Breast cancer surgery is safer for older women than has been assumed

NIHR | October 2020 |Breast cancer surgery is safer for older women than has been assumed

Between 2013-2018 over 3000 women aged 70 or over with operable breast cancer were recruited to a NIHR- funded cohort study. The majority (83.4 %) of the women underwent surgery; with researchers tracking their progress for two years. One of the study’s key findings is that no deaths were attributable to surgery for breast cancer. According to the authors of the study, this suggests that surgery for breast cancer in women in this age group is perhaps safer than thought.

This study is part of a wider- Bridging the Age Gaps in Breast Cancer- project which aims to examine the characteristics and outcomes (survival, quality of life and adverse events) of women aged at least 70 years in the UK undergoing surgery for breast cancer.

Researchers found:

• Fewer than one in five women (19.3%) had an adverse outcome, such as a dangerous blood clot (DVT) or wound pain.
• a woman’s age predicted what surgery she would receive. The oldest women in the group were twice as likely to have a mastectomy than the youngest women (59.1% vs 29.9%). Younger women were more likely to have breast-conserving surgery, with less breast tissue removed. This may relate to the lack of screening in older women, so cancers tend to be found when they are bigger and women feel a lump.
• older women were less likely to have lymph glands under the armpit removed (axillary surgery) than younger women (91.4% vs 98.6%). The aim of axillary surgery is to find out if the cancer has spread, and to remove any cancer in the axilla.
• just 2.8% of the women in this study who had a mastectomy went on to have reconstructive sugery. This compares to one in five (20%) women overall in the UK.
• quality of life was lower after surgery particularly for those who had more breast tissue removed as in mastectomy.
• the risk of being unable to carry out some standard day to day tasks was higher after surgery.

Morgan, J. L., George, J., Holmes, G., Martin, C., Reed, M. W., Ward, S., … & Wyld, L. (2020). Breast cancer surgery in older women: outcomes of the Bridging Age Gap in Breast Cancer study. British Journal of Surgery.

Abstract

Background

Breast cancer surgery in older women is variable and sometimes non‐standard owing to concerns about morbidity. Bridging the Age Gap in Breast Cancer is a prospective multicentre cohort study aiming to determine factors influencing treatment selection and outcomes from surgery for older patients with breast cancer.

Methods

Women aged at least 70 years with operable breast cancer were recruited from 57 UK breast units between 2013 and 2018. Associations between patient and tumour characteristics and type of surgery in the breast and axilla were evaluated using univariable and multivariable analyses. Oncological outcomes, adverse events and quality‐of‐life (QoL) outcomes were monitored for 2 years.

Results

Among 3375 women recruited, surgery was performed in 2816 patients, of whom 24 with inadequate data were excluded. Sixty‐two women had bilateral tumours, giving a total of 2854 surgical events. Median age was 76 (range 70–95) years. Breast surgery comprised mastectomy in 1138 and breast‐conserving surgery in 1716 procedures. Axillary surgery comprised axillary lymph node dissection in 575 and sentinel node biopsy in 2203; 76 had no axillary surgery. Age, frailty, dementia and co‐morbidities were predictors of mastectomy. Age, frailty and co‐morbidity were significant predictors of no axillary surgery. The rate of adverse events was moderate, with no 30‐day mortality. Long‐term QoL and functional independence were adversely affected by surgery.

Conclusion

Breast cancer surgery is safe in women aged 70 years or more, with serious adverse events being rare and no mortality. Age, ill health and frailty all influence surgical decision‐making. Surgery has a negative impact on QoL and independence, which must be considered when counselling patients about choices.

Full paper BJS Breast cancer surgery in older women: outcomes of the Bridging Age Gap in Breast Cancer study

Further information on the project is available from the University of Sheffield’s Medical School Bridging the Age Gap in Breast Cancer

Robotic surgery for rectal cancer produces similar results to keyhole surgery

NIHR Signal | December 2019 |Robotic surgery for rectal cancer produces similar results to keyhole surgery

Robotic rectal cancer surgery does not appear technically easier than standard keyhole surgery. The researchers, in this trial, judged this by measuring the need to ‘convert’ a keyhole procedure to open surgery when operating. This NIHR-funded trial also found that robotic surgery produced similar clinical results to standard laparoscopic (keyhole) surgery in treating rectal cancer.

In the trial, 28 out of 230 patients (12%) who received keyhole surgery were converted to open surgery, compared with 19 out of 236 (8%) who received robotic surgery. This difference did not achieve statistical significance. There were also no differences in the likelihood of removing the whole tumour, surgery-related complications and bladder or sexual function. Longer-term outcomes such as three-year recurrence and overall survival were also similar.

These results suggest robotic rectal surgery, which costs £1,000 more than laparoscopic surgery due to ongoing equipment costs and longer operating time, may not be cost-effective (Source: NIHR).

The full details of the trial are available from the NIHR 

Full reference:

Jayne, D. | 2019| Robotic-assisted Surgery Compared With Laparoscopic Resection Surgery for Rectal Cancer: The ROLARR RCT | Efficacy and Mechanism Evaluation | DOI: 10.3310/eme06100

Abstract

Background

Robotic rectal cancer surgery is gaining popularity, but there are limited data about its safety and efficacy. Objective To undertake an evaluation of robotic compared with laparoscopic rectal cancer surgery to determine its safety, efficacy and cost-effectiveness.

Design

This was a multicentre, randomised trial comparing robotic with laparoscopic rectal resection in patients with rectal adenocarcinoma.

Setting

The study was conducted at 26 sites across 10 countries and involved 40 surgeons. Participants The study involved 471 patients with rectal adenocarcinoma. Recruitment took place from 7 January 2011 to 30 September 2014 with final follow-up on 16 June 2015. Interventions Robotic and laparoscopic rectal cancer resections were performed by high anterior resection, low anterior resection or abdominoperineal resection. There were 237 patients randomised to robotic and 234 to laparoscopic surgery. Follow-up was at 30 days, at 6 months and annually until 3 years after surgery.

Main outcome measures The primary outcome was conversion to laparotomy. Secondary end points included intra- and postoperative complications, pathological outcomes, quality of life (QoL) [measured using the Short Form questionnaire-36 items version 2 (SF-36v2) and the Multidimensional Fatigue Inventory-20 (MFI-20)], bladder and sexual dysfunction [measured using the International Prostatic Symptom Score (I-PSS), the International Index of Erectile Function (IIEF) and the Female Sexual Function Index (FSFI)], and oncological outcomes. An economic evaluation considered the costs of robotic and laparoscopic surgery, including primary and secondary care costs up to 6 months post operation.

Results Among 471 randomised patients [mean age 64.9 years, standard deviation (SD) 11.0 years; 320 (67.9%) men], 466 (98.9%) patients completed the study. Data were analysed on an intention-to-treat basis. The overall rate of conversion to laparotomy was 10.1% and occurred in 19 (8.1%) patients in the robotic-assisted group and in 28 (12.2%) patients in the conventional laparoscopic group. Of the nine prespecified secondary end points, including circumferential resection margin positivity, intraoperative complications, postoperative complications, plane of surgery, 30-day mortality and bladder and sexual dysfunction, none showed a statistically significant difference between the groups. No difference between the treatment groups was observed for longer-term outcomes, disease-free and overall survival (OS). Males were at a greater risk of local recurrence than females and had worse OS rates. The costs of robotic and laparoscopic surgery, excluding capital costs, were £11,853 (SD £2940) and £10,874 (SD £2676) respectively.

Conclusions

There is insufficient evidence to conclude that robotic rectal surgery compared with laparoscopic rectal surgery reduces the risk of conversion to laparotomy. There were no statistically significant differences in resection margin positivity, complication rates or QoL at 6 months between the treatment groups. Robotic rectal cancer surgery was on average £980 more expensive than laparoscopic surgery, even when the acquisition and maintenance costs for the robot were excluded. Future work The lower rate of conversion to laparotomy in males undergoing robotic rectal cancer surgery deserves further investigation. The introduction of new robotic systems into the market may alter the cost-effectiveness of robotic rectal cancer surgery.

The full article is available from PubMed

New device accurately identifies cancer in seconds

Handheld device can identify cancerous tissue in 10 seconds, with 96% accuracy. | story via ScienceDaily

A team of scientists at The University of Texas has invented a handheld device that quickly and accurately identifies cancerous tissue during surgery, delivering results in about 10 seconds. The MasSpec Pen is a handheld instrument that gives surgeons precise diagnostic information about what tissue to cut or preserve, helping improve treatment and reduce the chances of cancer recurrence.

In tests on tissues removed from 253 human cancer patients, the MasSpec Pen took about 10 seconds to provide a diagnosis and was more than 96 percent accurate. The technology was also able to detect cancer in marginal regions between normal and cancer tissues that presented mixed cellular composition. The team expects to start testing this new technology during oncologic surgeries in 2018.

Full story at ScienceDaily

See also: BBC News: ‘Pen’ identifies cancer in 10 seconds

Full reference: Zhang, J. et al. Nondestructive tissue analysis for ex vivo and in vivo cancer diagnosis using a handheld mass spectrometry system  Science Translational Medicine 06 Sep 2017: Vol. 9, Issue 406

 

Prognosis following cancer surgery during holiday periods

This study aimed to test the new hypothesis that cancer surgery performed during holiday periods is associated with worse long-term prognosis than for non-holiday periods | International Journal of Cancer

This nationwide Swedish population-based cohort study included 228,927 patients during 1997-2014 who underwent elective resectional surgery for a cancer where the annual number of resections was over 100. The 16 eligible cancer sites were grouped into 10 cancer groups. The exposure, holiday periods, was classified as wide (14-weeks) or narrow (7-weeks). Surgery conducted inside versus outside holiday periods was compared regarding overall disease-specific (main outcome) and overall all-cause (secondary outcome) mortality.

Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, sex, comorbidity, hospital volume, calendar period, and tumor stage. Surgery conducted during wide and narrow holiday periods were associated with increased HRs of disease-specific mortality for cancer of the breast (HR 1.08, 95% CI 1.03-1.13 and HR 1.06, 95% CI 1.01-1.12) and possibly of cancer of the liver-pancreas-bile ducts (HR 1.09, 95% CI 0.99-1.20 and HR 1.12, 95% CI 0.99-1.26).

Sub-groups with cancer of the colon-rectum, head-and-neck, prostate, kidney-urine bladder, and thyroid also experienced statistically significantly worse prognosis following surgery conducted during holiday periods. No influence of surgery during holiday was detected for cancer of the esophagus-stomach, lung, or ovary-uterus. All-cause HRs were similar to the disease-specific HRs. The prognosis following cancer surgery might not be fully maintained during holiday periods for all cancer sites.

Full reference: Lagergren, J. et al. (2017) Prognosis following cancer surgery during holiday periods. International Journal of Cancer. Published online: 21 July 2017

Preoperative conventional chemoradiotherapy versus short-course radiotherapy with delayed surgery for rectal cancer

Latkauskas, T. et al. BMC Cancer. Published: 1 December 2016

Image source: Richard Kirsch and Raw’n’ Wild – Wellcome Images // CC BY-NC-ND 4.0

Background: There still is no evidence which neoadjuvant therapy regimen for stage II–III rectal cancer is superior. The aim of this study was to compare results achieved after long-course chemoradiotherapy (CRT) with short-term radiotherapy (RT) followed by delayed surgery.

 

Conclusion: Three-years disease-free survival was better in CRT group comparing with RT group with no difference in overall survival.

Read the full article here

Impact of laparoscopic versus open surgery on hospital costs for colon cancer

Laudicella, M. et al. (2016) BMJ Open. 6:e012977

Image source: Virginia Po – Wellcome Library // CC BY-NC-ND 4.0

Objective: Laparoscopy is increasingly being used as an alternative to open surgery in the treatment of patients with colon cancer. The study objective is to estimate the difference in hospital costs between laparoscopic and open colon cancer surgery.

Design: Population-based retrospective cohort study.

Settings: All acute hospitals of the National Health System in England.

Population: A total of 55 358 patients aged 30 and over with a primary diagnosis of colon cancer admitted for planned (elective) open or laparoscopic major resection between April 2006 and March 2013.

Primary outcomes: Inpatient hospital costs during index admission and after 30 and 90 days following the index admission.

Results: Propensity score matching was used to create comparable exposed and control groups. The hospital cost of an index admission was estimated to be £1933 (95% CI 1834 to 2027; p<0.01) lower among patients who underwent laparoscopic resection. After including the first unplanned readmission following index admission, laparoscopy was £2107 (95% CI 2000 to 2215; p<0.01) less expensive at 30 days and £2202 (95% CI 2092 to 2316; p<0.01) less expensive at 90 days. The difference in cost was explained by shorter hospital stay and lower readmission rates in patients undergoing minimal access surgery. The use of laparoscopic colon cancer surgery increased 4-fold between 2006 and 2012 resulting in a total cost saving in excess of £29.3 million for the National Health Service (NHS).

Conclusions: Laparoscopy is associated with lower hospital costs than open surgery in elective patients with colon cancer suitable for both interventions.

Read the full article here

Race/ethnicity and socio-economic differences in colorectal cancer surgery outcomes

Akinyemiju, T. et al. BMC Cancer. Published online: 5 September 2016

Image source: Wellcome Images // CC BY-NC-ND 4.0

Image shows photomicrograph of adenocarcinoma of the colon

Background: The purpose of this study was to examine racial and socio-economic differences in the receipt of laparoscopic or open surgery among patients with colorectal cancer, and to determine if racial and socio-economic differences exist in post-surgical complications, in-hospital mortality and hospital length of stay among patients who received surgery.

Methods: We conducted a cross-sectional analysis of hospitalized patients with a primary diagnosis of colorectal cancer between 2007 and 2011 using data from Nationwide Inpatient Sample. ICD-9 codes were used to capture primary diagnosis, surgical procedures, and health outcomes during hospitalization. We used logistic regression analysis to determine racial and socio-economic predictors of surgery type, post-surgical complications and mortality, and linear regression analysis to assess hospital length of stay.

Results: A total of 122,631 patients were admitted with a primary diagnosis of malignant colorectal cancer between 2007 and 2011. Of these, 17,327 (14.13 %) had laparoscopic surgery, 70,328 (57.35 %) received open surgery, while 34976 (28.52 %) did not receive any surgery. Black (36 %) and Hispanic (34 %) patients were more likely to receive no surgery compared with Whites (27 %) patients. However, among patients that received any surgery, there were no racial differences in which surgery was received (laparoscopic versus open, p = 0.2122), although socio-economic differences remained, with patients from lower residential income areas significantly less likely to receive laparoscopic surgery compared with patients from higher residential income areas (OR: 0.74, 95 % CI: 0.70-0.78). Among patients who received any surgery, Black patients (OR = 1.07, 95 % CI: 1.01-1.13), and patients with Medicare (OR = 1.16, 95 % CI: 1.11-1.22) and Medicaid (OR = 1.15, 95 % CI: 1.07-1.25) insurance experienced significantly higher post-surgical complications, in-hospital mortality (Black OR = 1.18, 95 % CI: 1.00-1.39), and longer hospital stay (Black β = 1.33, 95 % CI: 1.16-1.50) compared with White patients or patients with private insurance.

Conclusion: Racial and socio-economic differences were observed in the receipt of surgery and surgical outcomes among hospitalized patients with malignant colorectal cancer in the US.

Read the article here

Study shows patients require less painkilling medication after breast-cancer surgery if they have opiate-free anesthesia

ScienceDaily. Published online: 30 May 2016.

Image source: Fuse809 – Wikipedia // CC BY-SA 3.0

Image shows Remifentanil’s 3D molecular structure

In this study, painkiller requirements were examined after patients received opiate anaesthesia and non-opiate anaesthesia. A randomised controlled trial was conducted, containing two groups each containing 33 breast cancer patients undergoing a mastectomy or lumpectomy. The study took place between September 2014 and July 2015 at the Jules Bordet Institute, Brussels.

Perioperative non-opiate analgesia was obtained by combining clonidine (0.2 mcg/kg), ketamine (0.3 mg/kg) and lidocaine (1.5 mg/kg). An extra bolus of ketamine (0.2mg/kg) was given if necessary. Opiate analgesia was obtained via a combination of remifentanil infusion, ketamine (0.3 mg/kg) and lidocaine (1.5 mg/kg). Both groups received intravenous paracetamol (1000mg/6h) and intravenous diclofenac (75 mg/12h). Patients received a PCA (patient-controlled analgesia) pump for breakthrough pain during the first 24 hours post-operatively.

Clinical characteristics and post-operative piritramide painkiller consumption (through the patient controlled pump) were assessed during the first 24 hours post-operatively. Data were not complete for two patients in the non-opiate group, and thus a total of 64 patients were included in the study. The total mean piritramide usage 24 hours post-operatively was 8.1 mg (range 2.0-14.5) in the non-opiate group and 13.1 mg (range 6.0-16.0) in the opioid group. The difference observed was statistically significant.

Read the full commentary here

Environmental and social benefits of the targeted intraoperative radiotherapy for breast cancer

Coombs, N.J. et al. BMJ Open 2016. 6:e010703. 

Objective: To quantify the journeys and CO₂ emissions if women with breast cancer are treated with risk-adapted single-dose targeted intraoperative radiotherapy (TARGIT) rather than several weeks’ course of external beam whole breast radiotherapy (EBRT) treatment.

Setting: (1) TARGIT-A randomised clinical trial (ISRCTN34086741) which compared TARGIT with traditional EBRT and found similar breast cancer control, particularly when TARGIT was given simultaneously with lumpectomy, (2) 2 additional UK centres offering TARGIT.

Participants: 485 UK patients (249 TARGIT, 236 EBRT) in the prepathology stratum of TARGIT-A trial (where randomisation occurred before lumpectomy and TARGIT was delivered simultaneously with lumpectomy) for whom geographical data were available and 22 patients treated with TARGIT after completion of the TARGIT-A trial in 2 additional UK breast centres.

Outcome measures: The shortest total journey distance, time and CO₂ emissions from home to hospital to receive all the fractions of radiotherapy.

Methods: Distances, time and CO₂ emissions were calculated using Google Maps and assuming a fuel efficiency of 40 mpg. The groups were compared using the Student t test with unequal variance and the non-parametric Wilcoxon rank-sum (Mann-Whitney) test.

Results: TARGIT patients travelled significantly fewer miles: TARGIT 21 681, mean 87.1 (SE 19.1) versus EBRT 92 591, mean 392.3 (SE 30.2); had lower CO₂ emissions 24.7 kg (SE 5.4) vs 111 kg (SE 8.6) and spent less time travelling: 3 h (SE 0.53) vs 14 h (SE 0.76), all p<0.0001. Patients treated with TARGIT in 2 hospitals in semirural locations were spared much longer journeys (753 miles, 30 h, 215 kg CO₂ per patient).

Conclusions: The use of TARGIT intraoperative radiotherapy for eligible patients with breast cancer significantly reduces their journeys for treatment and has environmental benefits. If widely available, 5 million miles (8 000 000 km) of travel, 170 000 woman-hours and 1200 tonnes of CO₂ (a forest of 100 hectares) will be saved annually in the UK.

Read the full article here