Jamaoncology Bakouny 2021 L

Letters

Concept and design: Ortiz, Deshmukh. gland area of the United States (from March 2 to June 2, 2020),1 Acquisition, analysis, or interpretation of data: All authors. was compared with 3 control periods before and after the main Drafting of the manuscript: Ortiz, Colón-López, Deshmukh. Critical revision of the manuscript for important intellectual content: All authors. study period (the preceding 3 months from December 1, 2019, Statistical analysis: Ortiz-Ortiz, Tortolero-Luna, Torres-Cintrón, Deshmukh. to March 2, 2020; the same 3 months in the preceding year from Obtained funding: Ortiz, Colón-López, Deshmukh. March 2 to June 2, 2019; and the 3 months after the main study Administrative, technical, or material support: Ortiz, Wu, Deshmukh. period from June 3 to September 3, 2020). The percentage de- Supervision: Ortiz, Colón-López, Deshmukh. crease in screening tests and in diagnoses during the pan- ConflictofInterestDisclosures:DrOrtizreportedreceivinggrantsfromtheNational Institutes of Health during the conduct of the study; and personal fees from serving demic period compared with each of the control periods was as a consultant for Merck outside the submitted work. Dr Ortiz-Ortiz reported computed as percentage decrease = (Npandemic −Ncontrol)/ receiving grants from the Centers for Disease Control and Prevention (CDC) National Ncontrol. The 95% CIs were computed using the Clopper- Program of Cancer Registries and the National Cancer Institute (NCI) during the Pearson method using the DescTools package in R. All analy- conduct of the study; and grants from Abbvie Corp outside the submitted work. DrColón-LópezreportedrecevingpersonalfeesfromservingasaconsultantforMerck ses were performed using R, version 3.6.1 (R Foundation for & Co outside the submitted work. Dr Tortolero-Luna reported receiving grants from Statistical Computing) (eMethods in the Supplement). Ethi- the NCI and the CDC during the conduct of the study. Mr Torres-Cintrón reported cal approval for the study was provided by Brigham and Wo- receiving grants from CDC National Program of Cancer Registries during the conduct ofthestudy;andgrantsfromAbbVieCorpoutsidethesubmittedwork.DrDeshmukh men’s Hospital prior to commencement of data analysis, in- reportedreceivingpersonalfeesfromMerckIncoutsidethesubmittedwork.Noother cluding a waiver of the requirement for individual patient disclosures were reported. consent given the retrospective and noninterventional na- Funding/Support: This study was funded by U54 grant: 2U54CA096297-16, ture of the research. “Partnership for Excellence in Cancer Research between the University of Puerto Rico (UPR) and the University of Texas MD Anderson Cancer Center (MDACC)” and by award number NU58DP006318 from the National Program of Results | A total of 192 060 patients underwent screening dur- Cancer Registries of the Centers for Disease Control and Prevention to the ing the 4 screening periods. The overall mean (SD) age was 59.6 Puerto Rico Central Cancer Registry. (12.2) years, 58.6% of all patients were female, and 80.1% were Role of the Funder/Sponsor: The funding sources had no role in the design and non-Hispanic White. Overall, 15 453 patients (with 1985 ensu- conduct of the study; collection, management, analysis, and interpretation of ing diagnoses) had undergone 1 of the 5 cancer screening ex- the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. aminations (low-dose computed tomography,Papanicolaou test, AdditionalContributions:RyanSuk,MS,UTHealthSchoolofPublicHealth,provided colonoscopy, prostate-specific antigen screening, or mammog- assistance with Figure 2. She was not compensated for her contribution. raphy) during the 3-month pandemic study period, compared 1. Deshmukh AA, Suk R, Shiels MS, et al. Incidence trends and burden of human with 51 944 patients (3190 diagnoses) during the subsequent 3 papillomavirus–associated cancers among women in the United States, months, 64 269 patients (3423 diagnoses) in the preceding 3 2001-2017. J Natl Cancer Inst. 2020;djaa128. doi:10.1093/jnci/djaa128 months, and 60 344 patients (2961 diagnoses) during the same 2. Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint 3 months of the preceding year (2019). The decrease in screen- regression with applications to cancer rates. Stat Med. 2000;19(3):335-351. doi:10.1002/(SICI)1097-0258(20000215)19:3<335::AID-SIM336>3.0.CO;2-Z ing tests was accompanied by decreases in ensuing diagnoses 3. Rosenberg PS, Check DP, Anderson WF. A web tool for age-period-cohort and was found across the 5 screening tests (Figure 1). The per- analysis of cancer incidence and mortality rates. Cancer Epidemiol Biomarkers Prev. centage of positivity of screening tests appeared to be higher dur- 2014;23(11):2296-2302. doi:10.1158/1055-9965.EPI-14-0300 ing the primary pandemic period compared with the 3 control 4. Burger EA, Smith MA, Killen J, et al. Projected time to elimination of cervical periods for mammographies (4.1% vs 1.9%-2.3%), prostate- cancer in the USA: a comparative modelling study. Lancet Public Health. 2020;5 specific antigen screenings (22.7% vs 9.9%-13.2%), colonosco- (4):e213-e222. doi:10.1016/S2468-2667(20)30006-2 pies (1.3% vs 0.7%-0.9%), and Papanicolaou tests (11.6% vs 6.5%- 5. Centers for Disease Control and Prevention. BRFSS prevalence & trends data. Published 2020. Accessed September 3, 2020. https://www.cdc.gov/brfss/ 10.0%), but not for low-dose computed tomography scans (0.8% brfssprevalence/ vs 0.7%-0.8%). The percentage decreases in screening were pro- 6. Lei J, Ploner A, Elfström KM, et al. HPV vaccination and the risk of invasive nounced across all screening tests, compared with all 3 control cervical cancer. N Engl J Med. 2020;383(14):1340-1348. doi:10.1056/NEJMoa1917338 periods, and ranged from –60% to –82% (Figure 2A). The percentage decreases in diagnoses resulting from the cancer screen- Cancer Screening Tests and Cancer Diagnoses ing tests, compared with all 3 control periods, were also pro- During the COVID-19 Pandemic nounced (–19% to –78%; Figure 2B). Assuming the same number Oncology patient care may be disrupted secondary to corona- of patients (64 269) would have otherwise been screened dur- virus disease 2019 (COVID-19) through delays in diagnostic in- ing the pandemic period as in the previous 3 months, approxi- vestigations and surgical procedures, as well as delayed can- mately 1438 cancerous and precancerous lesion diagnoses (1985 cer diagnoses because of reduced cancer screening. This study vs 3423 diagnoses) were “missed” during the primary pan- assesses the number of pa- demic period.

Supplemental content tients undergoing cancer screening tests and of ensu- Discussion | This study reports a significant decrease in the num- ing cancer diagnoses during the COVID-19 pandemic in the larg- ber of patients undergoing screening tests for cancer and in the est health care system in the northeastern United States, Mas- number of ensuing diagnoses of cancerous and precancerous le- sachusetts General Brigham. sions during the COVID-19 pandemic in 1 health care system in the Northeastern United States. We found that, from June to Sep- Methods | This study comprised four 3-month periods. One pe- tember 2020, there was a significant recovery in the number of riod, during the first peak of the pandemic in the New En- screening tests and ensuing diagnoses, to almost prepandemic

458 JAMA Oncology March 2021 Volume 7, Number 3 (Reprinted) jamaoncology.com

Downloaded From: https://jamanetwork.com/ on 09/28/2021 Letters

Figure 1. Changes in the Numbers of Cancer Screening Tests and Ensuing Diagnoses

A B Subsequent 3 mo Pandemic group All tests Positive test results

Cancer screening test Cancer screening test Mammography Mammography PSA PSA Colonoscopy Colonoscopy Papanicolaou test Papanicolaou test Low-dose CT scan Low-dose CT scan

0 10 000 20 000 30 000 0 10 000 20 000 30 000 Screening tests, No. Screening tests, No.

C Preceding 3 mo D Same 3 mo in 2019

Cancer screening test Cancer screening test Mammography Mammography PSA PSA Colonoscopy Colonoscopy Papanicolaou test Papanicolaou test Low-dose CT scan Low-dose CT scan

0 10 000 20 000 30 000 0 10 000 20 000 30 000 Screening tests, No. Screening tests, No.

Changes in the numbers of cancer screening tests and ensuing diagnoses by cancer screening test and screening period during the primary pandemic study period compared with3controlperiods(subsequent3months,preceding3months,andsame3monthsintheprecedingyear).CTindicatescomputedtomography;PSA,prostate-specificantigen.

Figure 2. Percentage Decreases in the Numbers of Screening Tests and Ensuing Diagnoses

Subsequent 3 mo Preceding 3 mo Same 3 mo in 2019 A Screening tests

–10

–20

–30

–40

–50

–60

–70

Change in cancer screening tests, % –80

–90 Mammography PSA Colonoscopy Papanicolaou Low-dose test CT scan Cancer screening test

B Screening tests with diagnoses of cancerous or precancerous lesions

0 Percentage decreases during the primary pandemic study period –20 compared with 3 control periods –40 (subsequent 3 months, preceding 3 months, and same 3 months in the –60 preceding year) in the number of

Change in cancer diagnosis, % screening tests (A) and in the number –80 of screening tests leading to –100 diagnoses of cancerous or Mammography PSA Colonoscopy Papanicolaou Low-dose precancerous lesions (B). Error bars test CT scan indicate 95% CIs. CT indicates Cancer screening test computed tomography; PSA, prostate-specific antigen.

jamaoncology.com (Reprinted) JAMA Oncology March 2021 Volume 7, Number 3 459

Downloaded From: https://jamanetwork.com/ on 09/28/2021 Letters

levels. Moreover, we report that the number of potential “missed” COMMENT & RESPONSE diagnoses during the primary pandemic period were likely lower than would have been expected because the percentage of Effect of Adjuvant Paclitaxel and Carboplatin screening tests leading to a diagnosis of a cancerous or precan- on Survival in Early Triple-Negative Breast Cancer cerous lesion was higher during the primary pandemic period, To the Editor We read with great interest the results of the which may reflect the prioritization of high-risk patients for can- PATTERN (adjuvant Platinum and Taxane in Triple-Negative 1 cer screening during the pandemic. The limitations of this study Breast Cancer) randomized clinical trial by Yu et al that com- include the incomplete capture of the population of Massachu- pared 6 cycles of paclitaxel and carboplatin (PCb) vs anthra- setts and not accounting for patients who may have transitioned cycline-based adjuvant chemotherapy (cyclophosphamide, their screening procedures closer to home during the pandemic epirubicin, and fluorouracil) in early triple-negative breast can- to a clinician not captured in the network. cer (TNBC). Patients in the PCb arm had a 6.2% absolute benefit in disease-free survival (DFS) at 5 years (86.5% vs 80.3%; Ziad Bakouny, MD, MSc hazard ratio [HR], 0.65; 95% CI, 0.44-0.96; P = .03). The DFS Marco Paciotti, MD benefit did not translate into a statistically significant com- Andrew L. Schmidt, MD mensurate overall survival advantage, which was one of the Stuart R. Lipsitz, ScD secondary outcomes of the study. There are a few points that Toni K. Choueiri, MD need further discussion. Quoc-Dien Trinh, MD First, the contemporary preferred management of most patients with TNBC is neoadjuvant chemotherapy; this limits the Author Affiliations: Lank Center for Genitourinary Oncology, Department of clinical applicability of the study results to a few patients who Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts are treated with up-front surgery.2 In the select patient group of (Bakouny, Schmidt, Choueiri); Division of Urological Surgery, Brigham and Women’s Hospital, Boston, Massachusetts (Paciotti, Trinh); Center for Surgery early TNBC (comprising 74% node-negative and 54% pT1 1 and Public Health, Brigham and Women’s Hospital, Boston, Massachusetts tumors), the findings strengthen the conclusions of the West Ger- (Paciotti, Lipsitz, Trinh); Department of Urology, Humanitas Clinical and man Study PlanB trial3 that 6 cycles of an anthracycline-free regi- Research Center IRCCS, Rozzano, Italy (Paciotti). men (docetaxel and cyclophosphamide) were noninferior to an Accepted for Publication: November 3, 2020. anthracycline-based regimen (epirubicin and cyclophosphamide Published Online: January 14, 2021. doi:10.1001/jamaoncol.2020.7600 followed by docetaxel) in early ERBB2-negative breast cancer. Corresponding Authors: Toni K. Choueiri, MD, Department of Medical The outcomes were comparable in 445 of 2449 patients (18.2%) Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215 with TNBC and hormone-positive breast cancer. Although the ([email protected]); Quoc-Dien Trinh, MD, Center for Surgery and 4 Public Health, Brigham and Women’s Hospital, 75 Francis St, Boston, MA ABC (Anthracycline in Early Breast Cancer) trials failed to dem- ([email protected]). onstrate noninferiority of docetaxel and cyclophosphamide to Author Contributions: Drs Bakouny and Paciotti had full access to all the data anthracycline-based chemotherapy, the subgroup analysis of in the study and take responsibility for the integrity of the data and the accuracy 947 patients with node-negative TNBC did not show any bene- of the data analysis. Drs Bakouny, Paciotti and Schmidt are co–first authors. Drs Choueiri and Trinh are co–senior authors. fit of anthracyclines (HR, 1.31; 95% CI, 0.86-1.99). Thus, the 1 Concept and design: Bakouny, Schmidt, Lipsitz, Choueiri, Trinh. PATTERN trial adds to the evidence that an anthracycline-free Acquisition, analysis, or interpretation of data: All authors. regimen may be considered for patients with node-negative TNBC Drafting of the manuscript: Bakouny, Paciotti, Schmidt, Lipsitz. treated with up-front surgery. Critical revision of the manuscript for important intellectual content: Bakouny, Schmidt, Lipsitz, Choueiri, Trinh. Second, it is not clear whether the DFS benefit in the PCb arm Statistical analysis: Bakouny, Paciotti, Schmidt, Lipsitz. in the PATTERN trial1 was driven by carboplatin or weekly ad- Obtained funding: Choueiri. ministration of paclitaxel compared with docetaxel administered Administrative, technical, or material support: Schmidt, Choueiri. every 3 weeks. An exploratory analysis of the E1199 trial5 reported Supervision: Choueiri, Trinh. that weekly paclitaxel was substantially better than every-3- Conflict of Interest Disclosures: Dr Bakouny reported receiving grants from Genentech/IMCore and nonfinancial support from Bristol Myers Squibb outside weeks docetaxel in the TNBC cohort (10-year DFS: 69.0% vs the submitted work. Dr Schmidt reported receiving nonfinancial support from 62.3%; HR, 0.69; P = .001; overall survival: 75.1% vs 68.7%, HR, Astellas and Pfizer outside the submitted work. Dr Choueiri reported receiving 0.69; P = .02). It stands to reason that the improved DFS in the nonfinancial support from the COVID-19 and Cancer Consortium during the conduct of the study and personal fees from Pfizer, Exelixis, Bristol Myers PCb arm could be partly attributable to the difference in choice Squibb, Merck, Roche/Genentech, and Novartis related to kidney cancer for and schedule of taxane in the 2 treatment arms. clinical trials, to being on advisory boards, to consultancy, and to manuscript Lastly, it will be interesting to know the incidence of car- support outside the submitted work. Dr Trinh reported receiving personal fees diotoxic effects in the PATTERN trial. If it is higher in the from Astellas, Bayer, and Janssen and grants from Intuitive Surgical outside the submitted work. No other disclosures were reported. anthracycline arm, this further supports a non–anthracycline- Funding/Support: Dr Trinh is supported by a Health Services Research pilot based adjuvant treatment in patients with node-negative test grant from the Defense Health Agency and an unrestricted educational TNBC. grant from the Vattikutti Urology Institute. Role of the Funder/Sponsor: The funding sources had no role in the design and Shalabh Arora, MD conduct of the study; collection, management, analysis, and interpretation of Akash Kumar, DM the data; preparation, review, or approval of the manuscript; and decision to Atul Batra, DM submit the manuscript for publication. 1. Mass.gov.ArchiveofCOVID-19casesinMassachusetts.AccessedOctober25,2020. Author Affiliations: Department of Medical Oncology, Dr. BRA Institute Rotary https://www.mass.gov/info-details/archive-of-covid-19-cases-in-massachusetts Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.

460 JAMA Oncology March 2021 Volume 7, Number 3 (Reprinted) jamaoncology.com

Downloaded From: https://jamanetwork.com/ on 09/28/2021