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Sci Rep
Sci Rep
Scientific Reports
2045-2322
Nature Publishing Group UK London

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10.1038/s41598-024-71830-4
Article
Impact of COVID-19 pandemic on bone and soft tissue sarcoma patients’ consultation and diagnosis
Oyama Ryunosuke 1
Endo Makoto endo.m.a40@m.kyushu-u.ac.jp

1
Shimada Eijiro 1
Matsunobu Tomoya 2
Setsu Nokitaka 3
Ishihara Shin 3
Kanahori Masaya 1
Kawaguchi Kengo 1
Hirose Takeshi 1
Nabeshima Akira 1
Fujiwara Toshifumi 1
Yoshimoto Masato 2
Maekawa Akira 2
Hanada Masuo 2
Yokoyama Nobuhiko 3
Matsumoto Yoshihiro 4
Nakashima Yasuharu 1
1 https://ror.org/00p4k0j84 grid.177174.3 0000 0001 2242 4849 Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan
2 https://ror.org/01hky8m83 grid.415645.7 0000 0004 0378 8112 Department of Orthopaedic Surgery, Kyushu Rosai Hospital, Fukuoka, Japan
3 https://ror.org/00mce9b34 grid.470350.5 0000 0004 1774 2334 Department of Orthopaedic Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
4 https://ror.org/012eh0r35 grid.411582.b 0000 0001 1017 9540 Department of Orthopaedic Surgery, Fukushima Medical University, Fukushima, Japan
4 9 2024
4 9 2024
2024
14 206277 2 2024
30 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
The coronavirus disease (COVID-19) pandemic negatively affected the diagnosis and treatment of several cancer types. However, this pandemic’s exact impact and extent on bone and soft tissue sarcomas need to be clarified. We aimed to investigate the effect of the COVID-19 pandemic and emergency declaration by the local government on consultation behavior and clinical stage at diagnosis of bone and soft tissue sarcoma. A total of 403 patients diagnosed with bone and soft tissue sarcoma who initially visited three sarcoma treatment hospitals between January 2018 and December 2021 were included. The monthly number of newly diagnosed soft tissue sarcoma patients was reduced by 25%, and the proportion of soft tissue patients with stage IV disease at diagnosis significantly increased by 9% during the COVID-19 pandemic compared to before the COVID-19 pandemic. Furthermore, the monthly number of new primary bone and soft tissue sarcoma patients significantly decreased by 43% during the state of emergency declaration. The COVID-19 pandemic had a negative impact on soft tissue sarcoma patients’ consultation behavior and increased the proportion of advanced-stage patients at initial diagnosis. An emergency declaration by the local government also negatively affected primary bone and soft tissue sarcoma patients’ consultation behavior.

Keywords

COVID-19
Pandemic
Bone sarcoma
Soft tissue sarcoma
Consultation behavior
Subject terms

Medical research
Oncology
http://dx.doi.org/10.13039/501100001691 Japan Society for the Promotion of Science JP23K08700 Endo Makoto issue-copyright-statement© Springer Nature Limited 2024
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pmcIntroduction

Coronavirus disease (COVID-19) has spread worldwide since December 2019, and the first patient in Japan was confirmed in January 20201. Recent studies have shown that the COVID-19 pandemic was associated with fewer new diagnoses of several cancer types per month in various countries2–9. Particularly, cancers such as gastrointestinal, oral, and head and neck cancers were more susceptible to the reduction in screenings due to the COVID-19 pandemic, raising concerns about detection at more advanced stages10–12. In Japan, the pandemic has led to the postponement or cancellation of cancer screening13–16, delays in medical consultations, and an increase in the number of gastrointestinal cancers diagnosed as advanced17.

Regarding bone and soft tissue sarcomas, several reports also have shown the negative impact on patient’s diagnosis by the COVID-19 pandemic. The time from the first symptom to definitive histological diagnosis in patients with soft tissue sarcoma was delayed during the pandemic in Italy18. Furthermore, a study in Poland showed that the pandemic caused delays in performing biopsies of bone tumors19. However, there has been no report from Japan or other Asia countries regarding the impact of the COVID-19 pandemic on sarcoma patients.

During the COVID-19 pandemic, the government of the Fukuoka area in Japan declared a state of emergency to ask people to refrain from going out. It is unknown whether the emergency declaration, in a non-punitive manner, affected the consultation behavior of sarcoma patients during the COVID-19 pandemic.

The primary purpose of this study was to determine the impact of the COVID-19 pandemic on the consultation behavior of patients with bone and soft tissue sarcoma and its effect on the clinical stage at diagnosis. We also investigated the impact of the local government’s emergency declaration on the diagnosis of sarcomas through a collaboration among three major sarcoma treatment facilities in the Fukuoka area.

Results

A total of 403 new patients with bone and soft tissue sarcoma visited one of our hospitals between January 2018 and December 2021. Table 1 shows the number of new patients with bone and soft tissue sarcoma per month before and during the COVID-19 pandemic. Compared with before the COVID-19 pandemic, we did not observe a significant reduction in the number of overall new patients per month by 10% and in those of primary new patients by 15% during the COVID-19 pandemic, respectively. The number of new soft tissue sarcoma patients per month significantly decreased from 6.0 before the COVID pandemic to 4.5 during the COVID-19 pandemic (adjusted RR, 0.75; 95% confidence interval [CI] 0.58–0.96; p = 0.02), while there was no significant difference in the number of patients with bone sarcoma.Table 1 The number of new patients with bone and soft tissue sarcoma per month before and during COVID-19 pandemic.

Category	The number of new patients per month	Adjusted RR (95% CI)	p value	
Before
COVID-19	During
COVID-19 pandemic	
Overall	8.7	7.8	0.90 (0.74–1.10)	0.31	
Primary (Untreated elsewhere)	6.9	5.9	0.85 (0.68–1.10)	0.15	
Bone sarcoma	1.0	1.4	1.50 (0.90–2.60)	0.12	
Soft tissue sarcoma	6.0	4.5	0.75 (0.58–0.96)	0.02	
RR rate ratio, CI confidence interval.

Next, we examined the trends in the number of patients with bone and soft tissue sarcoma during the COVID-19 pandemic in more detail, focusing on the state of emergency declaration. The relative number of new patients with bone and soft tissue sarcoma during the COVID-19 pandemic is shown in Fig. 1, with the number of new patients before the COVID-19 pandemic set at 100. The number of new patients tended to be lower overall during the periods of state of emergency, highlighted by several colors. The number of new patients per month was aggregated for the five state-of-emergency periods and is summarized in Table 2. The monthly numbers of total new patients, newly diagnosed cases of primary patients not treated elsewhere, and those of primary soft tissue sarcoma were decreased significantly during states of emergency (p = 0.01, < 0.001, and 0.001, respectively) compared to before the COVID-19 pandemic.Fig. 1 Relative change in new bone and soft tissue sarcoma patients. Color-shaded areas refer to the state of emergency period. The number in the figure indicates a relative number of new patients when before the COVID-19 pandemic was set at 100.

Table 2 The number of new patients with bone and soft tissue sarcoma per month before COVID-19 pandemic and during states of emergency.

Category	The number of new patients per month	Adjusted RR (95% CI)	p value	
Before
COVID-19 pandemic	During
States of emergency	
Overall	8.7	6.1	0.68 (0.47–0.96)	0.01	
Primary (Untreated elsewhere)	6.9	3.9	0.56 (0.39–0.79)	 < .001	
Bone sarcoma	1.0	0.6	0.63 (0.23–1.5)	0.30	
Soft tissue sarcoma	6.0	3.3	0.55 (0.37–0.79)	0.001	
RR rate ratio, CI confidence interval.

Regarding the clinical stage of the primary soft tissue sarcoma patients, the proportion of stage IV patients was significantly higher during the COVID-19 pandemic (9% vs. 18%, p = 0.04) (Table 3 and Fig. 2). Regarding the other clinical characteristics, including age, location, and tumor size, there was no significant difference between before and during the COVID-19 pandemic.Table 3 The characteristics of primary (untreated elsewhere) soft tissue sarcoma patients before and during COVID-19 pandemic.

Category	Before
COVID-19
pandemic
N = 157	During
COVID-19
pandemic
N = 100	p value	
Age, mean (SD)	62.4 (20.1)	66.3 (17.8)	0.12	
Female, n (%)	73 (47)	49 (49)	0.79	
Location	
 Trunk	50 (32)	36 (36)	0.58	
 Extremity	107 (68)	64 (64)	
Size, n (%)	
 Tumor 10 cm or less	108 (71)	67 (67)	0.56	
 Tumor more than 10 cm	49 (29)	33 (33)	
Clinical stage, n (%)	
 I	25 (16)	10 (10)		
 II	22 (14)	15 (15)		
 III	88 (56)	53 (53)		
 IV	14 (9)	18 (18)	0.04*	
 Unknown	8 (5)	4 (4)		
Histology, n (%)	
 Myxofibrosarcoma	35 (22)	18 (18)		
 Dedifferentiated liposarcoma	32 (20)	19 (19)		
 Undifferentiated pleomorphic sarcoma	12 (8)	14 (14)		
 Myxoid liposarcoma	19 (12)	11 (11)		
 Leiomyosarcoma	16 (10)	12 (12)		
 Synovial sarcoma	9 (6)	6 (6)		
 Malignant peripheral nerve sheath tumor	10 (6)	3 (3)		
 Others	24 (16)	17 (17)		
*Stage I–II–III vs Stage IV.

Fig. 2 Proportion of clinical stages of primary soft tissue sarcoma patients before and during the coronavirus disease pandemic.

Figure 3 shows the proportion of sarcoma patients divided by the length from the onset of symptoms to the initial visit to a physician. For bone and soft tissue tumors, the proportion of patients who had their first visit within one month tended to be lower in the COVID-19 pandemic phase. However, there were no statistically significant differences. Regarding the interval from the initial visit to a physician to referral visit to specialist hospitals, the proportion of bone sarcoma patients who visited specialist hospitals within one month from the initial visit significantly increased during the pandemic (50 vs. 78%), as shown in Fig. 4.Fig. 3 Proportion of sarcoma patients per each interval length from the onset of symptoms to the initial visit to a physician.

Fig. 4 Proportion of sarcoma patients per each interval length from the initial visit to a physician to referral visit to specialist hospitals.

Discussion

This study investigated the impact of the COVID-19 pandemic and a state of emergency declaration on the consultation behavior of patients with bone and soft tissue sarcoma. In Japan, the first case of COVID-19 was reported in January 2020, and many medical facilities postponed nonurgent surgeries and cancer screening after March 2020, when the World Health Organization declared a pandemic. Furthermore, in the Fukuoka area, the government declared a state of emergency five times in response to the outbreak of COVID-19 infection and restricted people from leaving their homes unnecessarily.

Using a Poisson regression model, we evaluated the changes in the number of new patients per month between before and during the COVID-19 pandemic or the period of a state of emergency declaration. During the COVID-19 pandemic, the overall number of new patients per month decreased by 10%, and the number of primary patients decreased by 15%, but these differences were not statistically significant. A retrospective study using the national registry in Japan showed a substantial reduction of 12% in the diagnoses of gastric cancer, 11.5% in prostate cancer, and 8.3% in colon cancer during the COVID-19 pandemic20. The reduction rates were similar to those of other cancer types, but the lack of statistical significance might be due to the small samples. On the other hand, we observed a significant reduction in the numbers of overall new patients per month during the state of emergency by 32% and in those of primary new patients by 44% compared with before the COVID-19 pandemic, respectively. A substantial reduction in the number of new patients was observed during all five states of emergency, and a rebound was noted in the periods after the state of emergency declaration, as clearly shown in Fig. 1. The study on healthcare service use in Japan revealed that overall outpatient visits declined by 22% in May 2020, during the first state of emergency in Japan, with a decrease of 25% observed in orthopedics21. In our study, the number of new primary patients declined significantly by 43% during the same period and by 54% from August to October 2020. These results suggest that the state of emergency in Japan during the COVID-19 pandemic likely significantly impacted the decrease in the number of new patients with bone and soft tissue sarcoma.

We observed a significant reduction in the number of new patients with soft tissue sarcoma by 25% during the COVID-19 pandemic (6.0 vs. 4.5; p = 0.02) and by 45% during the state of emergency (6.0 vs. 3.3; p = 0.001) but did not observe the same trend in those with bone sarcoma during both periods. These results are consistent with the retrospective study in Italy involving 372 patients with soft tissue sarcoma that showed a significant reduction in the number of first visits and new diagnoses during March–May 2020 in the COVID group compared to the control group18. Moreover, a report in Poland involving 87 patients with bone tumors revealed that the pandemic resulted in delays in performing biopsies but did not affect the number of new diagnoses19. The discrepancy in diagnosis trends may be attributed to differences in the development and progression patterns between bone-derived and soft tissue-derived sarcomas. In general, patients with bone sarcomas often present pain due to increased pressure within the bone tissue caused by the expanding tumor mass in the limited space of the bone. Conversely, the initial symptom of patients with soft tissue sarcoma is frequently lump without pain. According to the descriptions on medical records about subjective symptoms related to the presence or absence of pain at the first visit, nearly 80% of patients with bone sarcoma present with pain, whereas only about 30% of patients with soft tissue sarcoma (data not shown). It is plausible that patients with painless lumps may have avoided consultation due to the fear of COVID-19 infection rather than seeking treatment for their symptoms.

In literature, some studies investigated whether the COVID-19 pandemic caused delays in cancer diagnosis, with varying results. In lung cancer, a report did not show delays in diagnosis or treatment initiation during the COVID-19 pandemic22. In contrast, a study reported delays in treatment due to the onset of the pandemic in breast cancer23. We observed that the proportion of patients who were seen first within one month from the onset of symptoms was decreased during the pandemic for bone sarcoma (46 vs. 39%, respectively) and soft tissue sarcoma (37 vs. 32%, respectively), but these differences were not statistically significant. On the other hand, the proportion of bone sarcoma patients who saw specialist hospitals within one month from the initial visit significantly increased during the pandemic (50 vs. 78%, respectively), and the proportion of those who took one to three months significantly decreased (38 vs. 11%, respectively). These results are similar to the study’s findings in Poland19. Daniel et al. reported that the median patient-related delay for patients with bone sarcoma was increased from 1 to 2 months during the pandemic, and the doctor-related delay was decreased from 5 to 3 months. This trend may reflect the diversity of symptoms or the complexity of the process from initial consultation to sarcoma diagnosis. These findings suggest that the period from the onset of symptoms to the initial visit can be particularly delayed in sarcoma patients during a pandemic. Therefore, it is crucial for healthcare institutions to continuously disseminate information about sarcoma and encourage patients with any symptoms to see hospitals promptly.

Previous studies have evaluated whether the COVID-19 pandemic impacted the cancer stage at diagnosis. The Italian COVID-DELAY study showed that new patients with colorectal, breast, and lung cancer in 2020 were less likely to be diagnosed with early stage and more likely with later stage22,24,25. In Japan, the number of patients diagnosed with stage I gastric and colorectal cancers was significantly decreased, and that with stage III colorectal cancer increased17. In this study, we observed a similar rise in the proportion of stage IV patients during the COVID-19 pandemic. Although it is unclear whether such later-stage diagnosis will have a consequential impact on survival, previous studies show the clinically relevant association of delays in diagnosis and treatment with poor outcomes for a range of cancer types26–30 and soft tissue sarcoma31–34. One modeling study in England examined the impact of the COVID-19 pandemic on cancer survival and suggested that delays of several months in the treatment would lead to a substantial proportion of many patients with early-stage cancers progressing to the incurable stages35. A delay in the diagnosis of sarcoma is prone to occur due to its rarity and heterogeneity in presentation. Given the absence of screening tests for sarcoma and the context mentioned above, the COVID-19 pandemic may adversely affect patient prognosis.

The negative impact of COVID-19 has underscored the need for enhanced preparedness for future pandemics. It is crucial to understand and address the problems of sarcoma patients, such as their scarcity, diverse histological types, weakened immune system, necessity for diagnosis and treatment by specialists, or limited treatment strategies when the disease progresses with a flexible and comprehensive approach. This includes raising awareness of the disease, stringent infection prevention measures, using telemedicine, setting treatment priorities and optimal allocation of medical resources, and collaboration among multidisciplinary teams36–38. Through these measures, we can ensure a safe and effective diagnosis or treatment environment for sarcoma patients.

Our study has several limitations. First, we only collected data from three hospitals, which might have limited the power of analyses, although those three hospitals are major sarcoma-treatment hospitals in the Fukuoka area. More representative results on the impact of the COVID-19 pandemic on bone and soft tissue sarcoma can be provided by including a larger sample of patients from more institutions. Second, this study could not evaluate outcomes other than a clinical-stage, such as overall or disease-free survival. It would be necessary for future studies to assess whether or not the COVID-19 pandemic is associated with those clinical outcomes for bone and soft tissue sarcoma patients.

In conclusion, the COVID-19 pandemic negatively impacted the early consultation of soft tissue sarcoma patients, increasing the proportion of stage IV patients at initial diagnosis. Also, the government’s emergency declaration led to the withholding of consultations by patients with primary bone and soft tissue tumors.

Methods

Study design and outcomes

This study included all bone and soft tissue sarcoma patients who had initially visited our hospitals, including Kyushu University Hospital, Kyushu Rosai Hospital, and Kyushu Cancer Center, between January 2018 and December 2021. Patients with an inconclusive pathological diagnosis of sarcoma were excluded from this study. Of 403 bone and soft tissue sarcoma patients, 315 were primary (untreated elsewhere) patients. Our hospitals include major sarcoma treatment facilities located in the Fukuoka area, which has a population of approximately 4 million, on Kyushu Island, Japan. We retrospectively collected the following data from medical charts and related documents: date of initial consultation at one of our hospitals, age, sex, symptoms, interval from onset of symptoms to the initial visit to a physician, interval from the initial visit to a physician to referral visit to specialist hospitals, size of the tumor, location of the tumor, bone or soft tissue tumor, histological diagnosis, and clinical stage at diagnosis based on the American Joint Committee on Cancer (AJCC) staging system39. Intervals from the onset of symptoms to the initial visit to a physician and from the initial visit to a physician to referral visit to specialist hospitals were classified into three categories (less than one month, one to three months, and more than three months) based on the previous literature40. For the analysis of the data on the intervals, 292 patients were included, as we excluded 23 cases with missing data. This study was conducted following the principles of the Declaration of Helsinki. The study protocol was approved by the Kyushu University Hospital Institutional Review Board (approval number: 22316-00) and the chief executive of Kyushu Rosai Hospital and Kyushu Cancer Center, respectively, under the laws of Japan41. Informed consent was obtained in the form of opt-out on the web-site. No patients were excluded from this study through opt-out.

The period of the COVID-19 pandemic and a state of emergency in the Fukuoka area

World Health Organization (WHO) characterized the outbreak of COVID-19 as a pandemic on 11 March 2020. Since the COVID-19 pandemic in the Fukuoka area began in March 2020, the period before the COVID-19 pandemic was defined as January 2018 to February 2020, and that during the COVID-19 pandemic in Japan was defined as March 2020 to December 2021 in this study. Within the above period, a state of emergency in the Fukuoka area was declared by the prefectural governments for the following five periods; (1) April 7 to May 14, 2020, (2) August 5 to October 8, 2020, (3) December 12, 2020 to February 28, 2021, (4) May 12 to June 20, 2021, (5) July 28 to October 11, 2021. We normalized the average monthly number of patients before the COVID-19 pandemic to 100 and calculated each period's relative increase or decrease.

Statistical analysis

Continuous variables were compared using a t-test, and chi-square tests were used to compare the proportions of categorical variables between groups. The rate ratio (RR) was analyzed using a Poisson regression model. A p-value of less than 0.05 indicated a statistically significant difference. All statistical analyses were conducted using JMP statistical software version 16.0 (SAS Institute).

Acknowledgements

The authors would like to thank Editage for the English language review. This work was partly supported by JSPS KAKENHI (Grant Number JP23K08700) and research funds from the Graduate School of Medical Sciences, Kyushu University. We thank Junji Kishimoto and Masayuki Hirose (Kyushu University) for their help with the statistical analysis. We also thank all members of Kyushu United for Exploration of Sarcoma Treatment (KUEST). This multi-institutional collaboration study was conducted as KUEST-1 study.

Author contributions

ME and YM were involved in the study conceptualization. RO, ME, TM, NS, MK, TH, AN, MY, AM, MH, NY, and YM contributed to the design of the work. RO, ME, ES, MK, TM, SN, AM, MY, and NY performed the data curation. RO, ME, ES, TM, NS, SI, MK, KK, TH, AN, MY, AM, MH, NY, and YM interpreted the data. ME, ES, TM, SN, SI, YM, YO, and YN supervised the project. All authors critically revised the report, commented on manuscript drafts, and approved the final report.

Data availability

The data supporting this study's findings are available from the corresponding author, ME, upon reasonable request.

Competing interests

The authors declare no competing interests.

Ethical approval

This study was conducted following the principles of the Declaration of Helsinki. The study protocol was approved by the Kyushu University Hospital Institutional Review Board (approval number: 22316-00) and the chief executive of Kyushu Rosai Hospital and Kyushu Cancer Center, respectively, under the laws of Japan. Informed consent was obtained in the form of opt-out on the web-site. Those who rejected it were excluded.

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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References

1. Furuse, Y. et al. Epidemiology of COVID-19 outbreak in Japan, January--March 2020. Jpn. J. Infect. Dis. JJID-2020 (2020).
2. Morris EJA Impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England: A population-based study Lancet Gastroenterol. Hepatol. 2021 6 199 208 10.1016/S2468-1253(21)00005-4 33453763
Morris, E. J. A. et al. Impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England: A population-based study. Lancet Gastroenterol. Hepatol. 6, 199–208 (2021).33453763 10.1016/S2468-1253(21)00005-4
3. Schrag D Hershman DL Basch E Oncology practice during the COVID-19 pandemic JAMA 2020 323 2005 2006 10.1001/jama.2020.6236 32282023
Schrag, D., Hershman, D. L. & Basch, E. Oncology practice during the COVID-19 pandemic. JAMA 323, 2005–2006 (2020).32282023 10.1001/jama.2020.6236
4. Johansson ALV The impact of the COVID-19 pandemic on cancer diagnosis based on pathology notifications: A comparison across the Nordic countries during 2020 Int. J. Cancer 2022 151 381 395 10.1002/ijc.34029 35419824
Johansson, A. L. V. et al. The impact of the COVID-19 pandemic on cancer diagnosis based on pathology notifications: A comparison across the Nordic countries during 2020. Int. J. Cancer 151, 381–395 (2022).35419824 10.1002/ijc.34029
5. Nicholson BD Consultations for clinical features of possible cancer and associated urgent referrals before and during the COVID-19 pandemic: An observational cohort study from English primary care Br. J. Cancer 2022 126 948 956 10.1038/s41416-021-01666-6 34934176
Nicholson, B. D. et al. Consultations for clinical features of possible cancer and associated urgent referrals before and during the COVID-19 pandemic: An observational cohort study from English primary care. Br. J. Cancer 126, 948–956 (2022).34934176 10.1038/s41416-021-01666-6
6. Coma E Impact of the COVID-19 pandemic and related control measures on cancer diagnosis in Catalonia: A time-series analysis of primary care electronic health records covering about five million people BMJ Open 2021 11 e047567 10.1136/bmjopen-2020-047567 34006554
Coma, E. et al. Impact of the COVID-19 pandemic and related control measures on cancer diagnosis in Catalonia: A time-series analysis of primary care electronic health records covering about five million people. BMJ Open 11, e047567 (2021).34006554 10.1136/bmjopen-2020-047567
7. Dinmohamed AG Fewer cancer diagnoses during the COVID-19 epidemic in the Netherlands Lancet Oncol. 2020 21 750 751 10.1016/S1470-2045(20)30265-5 32359403
Dinmohamed, A. G. et al. Fewer cancer diagnoses during the COVID-19 epidemic in the Netherlands. Lancet Oncol. 21, 750–751 (2020).32359403 10.1016/S1470-2045(20)30265-5
8. Rutter MD Brookes M Lee TJ Rogers P Sharp L Impact of the COVID-19 pandemic on UK endoscopic activity and cancer detection: a National Endoscopy Database Analysis Gut 2021 70 537 543 10.1136/gutjnl-2020-322179 32690602
Rutter, M. D., Brookes, M., Lee, T. J., Rogers, P. & Sharp, L. Impact of the COVID-19 pandemic on UK endoscopic activity and cancer detection: a National Endoscopy Database Analysis. Gut 70, 537–543 (2021).32690602 10.1136/gutjnl-2020-322179
9. Kaufman HW Chen Z Niles J Fesko Y Changes in the number of US patients with newly identified cancer before and during the coronavirus disease 2019 (COVID-19) pandemic JAMA Netw. Open 2020 3 e2017267 10.1001/jamanetworkopen.2020.17267 32749465
Kaufman, H. W., Chen, Z., Niles, J. & Fesko, Y. Changes in the number of US patients with newly identified cancer before and during the coronavirus disease 2019 (COVID-19) pandemic. JAMA Netw. Open 3, e2017267. 10.1001/jamanetworkopen.2020.17267 (2020).32749465 10.1001/jamanetworkopen.2020.17267
10. Kuzuu, K. et al. Changes in the number of gastrointestinal cancers and stage at diagnosis with COVID-19 pandemic in Japan: A multicenter cohort study. Cancers 15 (2023).
11. Lo Giudice G Increased delay in diagnosis, but not treatment, among patients with oral cancer during the COVID-19 pandemic JAMA Otolaryngol. Head Neck Surg. 2022 10.1001/jamaoto.2022.3652
Lo Giudice, G. et al. Increased delay in diagnosis, but not treatment, among patients with oral cancer during the COVID-19 pandemic. JAMA Otolaryngol. Head Neck Surg.10.1001/jamaoto.2022.3652 (2022).10.1001/jamaoto.2022.3652
12. Tevetoğlu F Kara S Aliyeva C Yıldırım R Yener HM Delayed presentation of head and neck cancer patients during COVID-19 pandemic Eur. Arch. Otorhinolaryngol. 2021 278 5081 5085 10.1007/s00405-021-06728-2 33674926
Tevetoğlu, F., Kara, S., Aliyeva, C., Yıldırım, R. & Yener, H. M. Delayed presentation of head and neck cancer patients during COVID-19 pandemic. Eur. Arch. Otorhinolaryngol. 278, 5081–5085 (2021).33674926 10.1007/s00405-021-06728-2
13. Fujita, M. et al. Changes in the number of cancer diagnosis practices due to the COVID-19 pandemic: Interrupted time-series analysis using the National Database of Japan. J. Cancer Res. Clin. Oncol. 1–11 (2023).
14. Nogami Y Impact of COVID-19 on gynecologic cancer treatment in Japan: A nationwide survey by the Japan Society of Gynecologic Oncology (JSGO) J. Gynecol. Oncol. 2022 33 e8 10.3802/jgo.2022.33.e8 34783211
Nogami, Y. et al. Impact of COVID-19 on gynecologic cancer treatment in Japan: A nationwide survey by the Japan Society of Gynecologic Oncology (JSGO). J. Gynecol. Oncol. 33, e8 (2022).34783211 10.3802/jgo.2022.33.e8
15. Nogami, Y. et al. Impact of COVID-19 on cervical cancer screening in Japan: A survey of population-based screening in urban Japan by the Japan Society of Gynecologic Oncology. J. Obstet. Gynaecol. Res. (2021).
16. Toyoda Y Katanoda K Ishii K Yamamoto H Tabuchi T Negative impact of the COVID-19 state of emergency on breast cancer screening participation in Japan Breast Cancer 2021 28 1340 1345 10.1007/s12282-021-01272-7 34241799
Toyoda, Y., Katanoda, K., Ishii, K., Yamamoto, H. & Tabuchi, T. Negative impact of the COVID-19 state of emergency on breast cancer screening participation in Japan. Breast Cancer 28, 1340–1345 (2021).34241799 10.1007/s12282-021-01272-7
17. Kuzuu K Gastrointestinal cancer stage at diagnosis before and during the COVID-19 pandemic in Japan JAMA Netw. Open 2021 4 e2126334 e2126334 10.1001/jamanetworkopen.2021.26334 34546368
Kuzuu, K. et al. Gastrointestinal cancer stage at diagnosis before and during the COVID-19 pandemic in Japan. JAMA Netw. Open 4, e2126334–e2126334 (2021).34546368 10.1001/jamanetworkopen.2021.26334
18. Onesti CE The impact of the COVID-19 pandemic on diagnosis and treatment of patients with soft tissue and bone sarcomas or aggressive benign musculoskeletal diseases: A single-center retrospective study (SarCorD study) Front. Oncol. 2022 12 1000056 10.3389/fonc.2022.1000056 36249051
Onesti, C. E. et al. The impact of the COVID-19 pandemic on diagnosis and treatment of patients with soft tissue and bone sarcomas or aggressive benign musculoskeletal diseases: A single-center retrospective study (SarCorD study). Front. Oncol. 12, 1000056 (2022).36249051 10.3389/fonc.2022.1000056
19. Kotrych, D. et al. Delay in diagnosis and treatment of primary bone tumors during COVID-19 pandemic in Poland. Cancers 14 (2022).
20. Horita N Impact of the COVID-19 pandemic on cancer diagnosis and resection in a COVID-19 low-burden country: Nationwide registration study in Japan Eur. J. Cancer 2022 165 113 115 10.1016/j.ejca.2022.01.027 35231766
Horita, N. Impact of the COVID-19 pandemic on cancer diagnosis and resection in a COVID-19 low-burden country: Nationwide registration study in Japan. Eur. J. Cancer 165, 113–115 (2022).35231766 10.1016/j.ejca.2022.01.027
21. Yamaguchi S Impact of COVID-19 pandemic on healthcare service use for non-COVID-19 patients in Japan: Retrospective cohort study BMJ Open 2022 12 e060390 10.1136/bmjopen-2021-060390 35466081
Yamaguchi, S. et al. Impact of COVID-19 pandemic on healthcare service use for non-COVID-19 patients in Japan: Retrospective cohort study. BMJ Open 12, e060390 (2022).35466081 10.1136/bmjopen-2021-060390
22. Cantini L Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): Fewer cases and higher stages from a real-world scenario ESMO Open 2022 7 100406 10.1016/j.esmoop.2022.100406 35219245
Cantini, L. et al. Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): Fewer cases and higher stages from a real-world scenario. ESMO Open 7, 100406 (2022).35219245 10.1016/j.esmoop.2022.100406
23. Papautsky EL Hamlish T Patient-reported treatment delays in breast cancer care during the COVID-19 pandemic Breast Cancer Res. Treat. 2020 184 249 254 10.1007/s10549-020-05828-7 32772225
Papautsky, E. L. & Hamlish, T. Patient-reported treatment delays in breast cancer care during the COVID-19 pandemic. Breast Cancer Res. Treat. 184, 249–254 (2020).32772225 10.1007/s10549-020-05828-7
24. Mentrasti G Alarming drop in early stage colorectal cancer diagnoses after COVID-19 outbreak: A real-world analysis from the Italian COVID-DELAY study Oncologist 2022 27 e723 e730 10.1093/oncolo/oyac129 35815922
Mentrasti, G. et al. Alarming drop in early stage colorectal cancer diagnoses after COVID-19 outbreak: A real-world analysis from the Italian COVID-DELAY study. Oncologist 27, e723–e730 (2022).35815922 10.1093/oncolo/oyac129
25. Mentrasti G Rising incidence of late stage breast cancer after COVID-19 outbreak. Real-world data from the Italian COVID-DELAY study Breast 2022 65 164 171 10.1016/j.breast.2022.08.007 35998429
Mentrasti, G. et al. Rising incidence of late stage breast cancer after COVID-19 outbreak. Real-world data from the Italian COVID-DELAY study. Breast 65, 164–171 (2022).35998429 10.1016/j.breast.2022.08.007
26. Brenkman HJF Association between waiting time from diagnosis to treatment and survival in patients with curable gastric cancer: A population-based study in the Netherlands Ann. Surg. Oncol. 2017 24 1761 1769 10.1245/s10434-017-5820-8 28353020
Brenkman, H. J. F. et al. Association between waiting time from diagnosis to treatment and survival in patients with curable gastric cancer: A population-based study in the Netherlands. Ann. Surg. Oncol. 24, 1761–1769 (2017).28353020 10.1245/s10434-017-5820-8
27. Hangaard Hansen C Gögenur M Tvilling Madsen M Gögenur I The effect of time from diagnosis to surgery on oncological outcomes in patients undergoing surgery for colon cancer: A systematic review Eur. J. Surg. Oncol. 2018 44 1479 1485 10.1016/j.ejso.2018.06.015 30251641
Hangaard Hansen, C., Gögenur, M., Tvilling Madsen, M. & Gögenur, I. The effect of time from diagnosis to surgery on oncological outcomes in patients undergoing surgery for colon cancer: A systematic review. Eur. J. Surg. Oncol. 44, 1479–1485 (2018).30251641 10.1016/j.ejso.2018.06.015
28. Hanna TP Mortality due to cancer treatment delay: Systematic review and meta-analysis BMJ 2020 371 m4087 10.1136/bmj.m4087 33148535
Hanna, T. P. et al. Mortality due to cancer treatment delay: Systematic review and meta-analysis. BMJ 371, m4087 (2020).33148535 10.1136/bmj.m4087
29. Lee Y-H Effect of length of time from diagnosis to treatment on colorectal cancer survival: A population-based study PLoS One 2019 14 e0210465 10.1371/journal.pone.0210465 30640932
Lee, Y.-H. et al. Effect of length of time from diagnosis to treatment on colorectal cancer survival: A population-based study. PLoS One 14, e0210465 (2019).30640932 10.1371/journal.pone.0210465
30. Toes-Zoutendijk E Impact of COVID-19 and suspension of colorectal cancer screening on incidence and stage distribution of colorectal cancers in the Netherlands Eur. J. Cancer 2022 161 38 43 10.1016/j.ejca.2021.11.008 34915408
Toes-Zoutendijk, E. et al. Impact of COVID-19 and suspension of colorectal cancer screening on incidence and stage distribution of colorectal cancers in the Netherlands. Eur. J. Cancer 161, 38–43 (2022).34915408 10.1016/j.ejca.2021.11.008
31. Urakawa H Association of short duration from initial symptoms to specialist consultation with poor survival in soft-tissue sarcomas Am. J. Clin. Oncol. 2015 38 266 271 10.1097/COC.0b013e318295aea2 23648441
Urakawa, H. et al. Association of short duration from initial symptoms to specialist consultation with poor survival in soft-tissue sarcomas. Am. J. Clin. Oncol. 38, 266–271 (2015).23648441 10.1097/COC.0b013e318295aea2
32. Nandra R Hwang N Matharu GS Reddy K Grimer R One-year mortality in patients with bone and soft tissue sarcomas as an indicator of delay in presentation Ann. R. Coll. Surg. Engl. 2015 97 425 433 10.1308/003588415X14181254790284 26274756
Nandra, R., Hwang, N., Matharu, G. S., Reddy, K. & Grimer, R. One-year mortality in patients with bone and soft tissue sarcomas as an indicator of delay in presentation. Ann. R. Coll. Surg. Engl. 97, 425–433 (2015).26274756 10.1308/003588415X14181254790284
33. Nakamura T The symptom-to-diagnosis delay in soft tissue sarcoma influence the overall survival and the development of distant metastasis J. Surg. Oncol. 2011 104 771 775 10.1002/jso.22006 21744348
Nakamura, T. et al. The symptom-to-diagnosis delay in soft tissue sarcoma influence the overall survival and the development of distant metastasis. J. Surg. Oncol. 104, 771–775 (2011).21744348 10.1002/jso.22006
34. Featherall J Time to treatment initiation and survival in adult localized, high-grade soft tissue sarcoma J. Surg. Oncol. 2019 120 1241 1251 10.1002/jso.25719 31587292
Featherall, J. et al. Time to treatment initiation and survival in adult localized, high-grade soft tissue sarcoma. J. Surg. Oncol. 120, 1241–1251 (2019).31587292 10.1002/jso.25719
35. Loveday C Prioritisation by FIT to mitigate the impact of delays in the 2-week wait colorectal cancer referral pathway during the COVID-19 pandemic: A UK modelling study Gut 2021 70 1053 1060 10.1136/gutjnl-2020-321650 32855306
Loveday, C. et al. Prioritisation by FIT to mitigate the impact of delays in the 2-week wait colorectal cancer referral pathway during the COVID-19 pandemic: A UK modelling study. Gut 70, 1053–1060 (2021).32855306 10.1136/gutjnl-2020-321650
36. Alami H How can health systems better prepare for the next pandemic? Lessons learned from the management of COVID-19 in Quebec (Canada) Front. Public Health 2021 9 671833 10.3389/fpubh.2021.671833 34222176
Alami, H. et al. How can health systems better prepare for the next pandemic? Lessons learned from the management of COVID-19 in Quebec (Canada). Front. Public Health 9, 671833 (2021).34222176 10.3389/fpubh.2021.671833
37. Davidson NE Cancer care at the beginning of the COVID-19 pandemic: Effects on patients and early interventions to mitigate stresses on care Cancer J. 2022 28 107 110 10.1097/PPO.0000000000000586 35333494
Davidson, N. E. et al. Cancer care at the beginning of the COVID-19 pandemic: Effects on patients and early interventions to mitigate stresses on care. Cancer J. 28, 107–110 (2022).35333494 10.1097/PPO.0000000000000586
38. Gatellier L Preparing for the next pandemic: An Asian National Cancer Centers Alliance (ANCCA) Initiative Asian Pac. J. Cancer Prev. 2021 22 2945 2950 10.31557/APJCP.2021.22.9.2945 34582666
Gatellier, L. et al. Preparing for the next pandemic: An Asian National Cancer Centers Alliance (ANCCA) Initiative. Asian Pac. J. Cancer Prev. 22, 2945–2950 (2021).34582666 10.31557/APJCP.2021.22.9.2945
39. Tanaka K Ozaki T New TNM classification (AJCC eighth edition) of bone and soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group Jpn. J. Clin. Oncol. 2019 49 103 107 10.1093/jjco/hyy157 30423153
Tanaka, K. & Ozaki, T. New TNM classification (AJCC eighth edition) of bone and soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group. Jpn. J. Clin. Oncol. 49, 103–107 (2019).30423153 10.1093/jjco/hyy157
40. Soomers VLMN Patient and diagnostic intervals of survivors of sarcoma: Results from the SURVSARC study Cancer 2020 126 5283 5292 10.1002/cncr.33181 33002193
Soomers, V. L. M. N. et al. Patient and diagnostic intervals of survivors of sarcoma: Results from the SURVSARC study. Cancer 126, 5283–5292 (2020).33002193 10.1002/cncr.33181
41. Eba J Nakamura K Overview of the ethical guidelines for medical and biological research involving human subjects in Japan Jpn. J. Clin. Oncol. 2022 52 539 544 10.1093/jjco/hyac034 35349681
Eba, J. & Nakamura, K. Overview of the ethical guidelines for medical and biological research involving human subjects in Japan. Jpn. J. Clin. Oncol. 52, 539–544 (2022).35349681 10.1093/jjco/hyac034
