Comprehensive Geriatric Assessment for Older Women with Early-Stage (Non-Metastatic) Breast Cancer—An Updated Systematic Review of the Literature
and Kwok-Leung Cheung 1,2,*
Gretchen G. Kimmick
Round 1
Reviewer 1 Report
The authors gathered reports from the literature regarding geriatric assessment and its use in patients with early stage breast cancer. Each study is outlined in tabular form and briefly summarized in the text.
Specific comments:
- The body of the manuscript indicates that the focus was to compile data about GA in patients with early-stage (non-metastatic) breast cancer. The title, therefore, should be changed to reflect this. “Primary breast cancer” does not indicate a specific stage, only that it was the cancer of the breast that was the primary.
- In the methods, please clarify search terms to clarify stage of breast cancer patients in the studies.
- CGA is a broad term including assessment of multiple domains important to older persons. The typically included domains are functional status, falls, comorbidity, nutrition, psychological and spiritual status, cognition, polypharmacy, social support. In the methods, please describe what criteria were used to define CGA. Did all reports have to include certain domains assessed or did the paper just need to call the assessment a “CGA”.
- In the description of the Critical Appraisal in Methods, please include more explanation of the criteria used and a supporting reference or references.
- Mention is missing of the following references, and others that are pertinent to this review, that included women with early-stage breast cancer:
· Magnuson, A, MS Sedrak, CP Gross, WP Tew, HD Klepin, TM Wildes, HB Muss, E Dotan, RA Freedman, T O'Connor, W Dale, HJ Cohen, V Katheria, A Arsenyan, A Levi, H Kim, S Mohile, A Hurria and CL Sun (2021). "Development and Validation of a Risk Tool for Predicting Severe Toxicity in Older Adults Receiving Chemotherapy for Early-Stage Breast Cancer." J Clin Oncol 39(6): 608-618. https://doi.org/10.1200/JCO.20.02063
· Extermann, M, I Boler, RR Reich, GH Lyman, RH Brown, J DeFelice, RM Levine, ET Lubiner, P Reyes, FJ Schreiber, 3rd and L Balducci (2012). "Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score." Cancer 118(13): 3377-3386. https://doi.org/10.1002/cncr.26646
· Hurria, A, E Soto-Perez-de-Celis, JB Allred, HJ Cohen, A Arsenyan, K Ballman, J Le-Rademacher, A Jatoi, J Filo, J Mandelblatt, JM Lafky, G Kimmick, HD Klepin, RA Freedman, H Burstein, J Gralow, AC Wolff, G Magrinat, M Barginear and H Muss (2019). "Functional Decline and Resilience in Older Women Receiving Adjuvant Chemotherapy for Breast Cancer." J Am Geriatr Soc 67(5): 920-927. https://doi.org/10.1111/jgs.15493
· Kikuchi, R, G Broadwater, R Shelby, J Robertson, LL Zullig, B Maloney, C Meyer, D Mungal, PK Marcom, R Kanesvaran, H White and G Kimmick (2019). "Detecting geriatric needs in older patients with breast cancer through use of a brief geriatric screening tool." J Geriatr Oncol 10(6): 968-972. https://doi.org/10.1016/j.jgo.2019.04.010
· Extermann, M, C Vonnes, B Dosal, J Mcclennon and R Reich (2019). "Integrating geriatric screening in the clinical trial setting with the SAOP-3: Recommendations for screening older adults undergoing cancer treatments " Journal of Geriatric Oncology 10 (6 Supplement 1 ): S91.
· Bartlett, DB, G Broadwater, HK White, R Shelby, LL Zullig, J Robertson, R Kanesvaran, HJ Cohen and G Kimmick (2020). "Factors associated with falls in older women with breast cancer: the use of a brief geriatric screening tool in clinic." Breast Cancer Res Treat 184(2): 445-457. https://doi.org/10.1007/s10549-020-05862-5
· Dale, W, HD Klepin, GR Williams, SMH Alibhai, C Bergerot, K Brintzenhofeszoc, JO Hopkins, MP Jhawer, V Katheria, KP Loh, LM Lowenstein, JM McKoy, V Noronha, T Phillips, AE Rosko, T Ruegg, MK Schiaffino, JF Simmons, Jr., I Subbiah, WP Tew, TL Webb, M Whitehead, MR Somerfield and SG Mohile (2023). "Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Systemic Cancer Therapy: ASCO Guideline Update." J Clin Oncol, 10.1200/JCO.23.00933: JCO2300933. https://doi.org/10.1200/JCO.23.00933
· Mohile, SG, MR Mohamed, H Xu, E Culakova, KP Loh, A Magnuson, MA Flannery, S Obrecht, N Gilmore, E Ramsdale, RF Dunne, T Wildes, S Plumb, A Patil, M Wells, L Lowenstein, M Janelsins, K Mustian, JO Hopkins, J Berenberg, N Anthony and W Dale (2021). "Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study." Lancet 398(10314): 1894-1904. https://doi.org/10.1016/S0140-6736(21)01789-X
· Webster, S, S Lawn, R Chan and B Koczwara (2020). "The role of comorbidity assessment in guiding treatment decision-making for women with early breast cancer: a systematic literature review." Support Care Cancer 28(3): 1041-1050. https://doi.org/10.1007/s00520-019-05218-w
· de Boer, AZ, W van de Water, E Bastiaannet, NA de Glas, M Kiderlen, JEA Portielje and M Extermann (2020). "Early stage breast cancer treatment and outcome of older patients treated in an oncogeriatric care and a standard care setting: an international comparison." Breast Cancer Res Treat 184(2): 519-526. https://doi.org/10.1007/s10549-020-05860-7
· Williams, GR, AM Deal, HK Sanoff, KA Nyrop, EJ Guerard, M Pergolotti, SS Shachar, BB Reeve, JT Bensen, SK Choi and HB Muss (2019). "Frailty and health-related quality of life in older women with breast cancer." Support Care Cancer 27(7): 2693-2698. https://doi.org/10.1007/s00520-018-4558-6
· Dottorini, L, L Catena, I Sarno, G Di Menna, A Marte, E Novelli, C Rusca and E Bajetta (2019). "The role of Geriatric screening tool (G8) in predicting side effect in older patients during therapy with aromatase inhibitor." J Geriatr Oncol 10(2): 356-358. https://doi.org/10.1016/j.jgo.2018.10.007
· Thomas, R, A Pieri and H Cain (2017). "A systematic review of generic and breast cancer specific life expectancy models in the elderly." Eur J Surg Oncol 43(10): 1816-1827. https://doi.org/10.1016/j.ejso.2017.06.014
- There are several reports from CALGB 49907 and CALGB 369901 that would be pertinent to the discussion, including the following:
· Dura-Ferrandis, E, JS Mandelblatt, J Clapp, G Luta, L Faul, G Kimmick, HJ Cohen, RL Yung and A Hurria (2017). "Personality, coping, and social support as predictors of long-term quality-of-life trajectories in older breast cancer survivors: CALGB protocol 369901 (Alliance)." Psychooncology, 10.1002/pon.4404. https://doi.org/10.1002/pon.4404
· Mandelblatt, JS, L Cai, G Luta, G Kimmick, J Clapp, C Isaacs, B Pitcher, W Barry, E Winer, S Sugarman, C Hudis, H Muss, HJ Cohen and A Hurria (2017). "Frailty and long-term mortality of older breast cancer patients: CALGB 369901 (Alliance)." Breast Cancer Res Treat 164(1): 107-117. https://doi.org/10.1007/s10549-017-4222-8
- Section 4.2 includes references to work related to advanced cancer (ex 15, 31, 32), not breast cancer, and seems disjointed. There is other work that is pertinent (see reference).
· Thomas, R, A Pieri and H Cain (2017). "A systematic review of generic and breast cancer specific life expectancy models in the elderly." Eur J Surg Oncol 43(10): 1816-1827. https://doi.org/10.1016/j.ejso.2017.06.014
· Kimmick, GG, B Major, J Clapp, J Sloan, B Pitcher, K Ballman, M Barginear, RA Freedman, A Artz, HD Klepin, JM Lafky, J Hopkins, E Winer, C Hudis, H Muss, H Cohen, A Jatoi, A Hurria and J Mandelblatt (2017). "Using ePrognosis to estimate 2-year all-cause mortality in older women with breast cancer: Cancer and Leukemia Group B (CALGB) 49907 and 369901 (Alliance A151503)." Breast Cancer Res Treat 163(2): 391-398. https://doi.org/10.1007/s10549-017-4188-6
- On line 201, please specify which ‘biomarkers’ these are.
- The sentence on lines 202 and 203 seems out of place and the supporting reference is to a review paper.
- Reference 31, does not seem pertinent to extent of breast surgery and should be checked.
- The sentence on line 207 pertains to renal cell carcinoma, but the reference 32 is about patients with lymphoma.
- How is the study of Stotter et al akin to the prior mentioned study? Were the tools similar? How was treatment decision-making affected?
- The summary on lines 212 and 213 is not well supported by the evidence provided.
- Regarding the statement that the G8 is the most common screening tool (line 265), the qualifier should be included that there is the most literature about the G8. It may not be the most common tool, as is alluded to later in the paper.
There are grammatical errors on the following lines:
- 30 and 33, “frailer” should be replace with “more frail”
- 44, missing word between ‘consists’ and ‘assessment
- 50, ‘with’ should be ‘which’
- 60, ‘according’ should be ‘accordance’
- 66, the Parks reference is 2012, not 2011
- 69, dates missing after the word ‘between’
- 78, study type is listed twice
- 104, ‘functional’ should be ‘function’
- 225, ‘use of how’?
- 244, perhaps there is an extra word? ‘a’ or ‘to’?
- 256, extra word, ‘in’, should be deleted
- 283, ‘that a full CGA’ what?
There are also multiple misspelled words and typos in the references.
See comments to authors.
Author Response
Comment 1: The body of the manuscript indicates that the focus was to compile data about GA in patients with early-stage (non-metastatic) breast cancer. The title, therefore, should be changed to reflect this. “Primary breast cancer” does not indicate a specific stage, only that it was the cancer of the breast that was the primary.
Response 1: The title has been amended.
Comment 2: In the methods, please clarify search terms to clarify stage of breast cancer patients in the studies.
Response 2: This review is an updated systematic review of the literature that was initially conducted by our team in 2012. To allow for accurate comparison between the two reviews, and to further evaluate the new literature published, the methodology from the previous review and the new review must be kept the same. This included the search terms that were used. As with the original review, we did not use search terms that specified the stage of the breast cancer, we will not be able to add any additional search terms. After applying our exclusion/ inclusion criteria, we were able to identify the stage of breast cancer that the studies focused on (Table 1). This is perhaps a flaw within our original methodology, and a factor we will take into consideration for future work.
Comment 3: CGA is a broad term including assessment of multiple domains important to older persons. The typically included domains are functional status, falls, comorbidity, nutrition, psychological and spiritual status, cognition, polypharmacy, social support. In the methods, please describe what criteria were used to define CGA. Did all reports have to include certain domains assessed or did the paper just need to call the assessment a “CGA”.
Response 3: Similarly, to the above response (Response 2), our methods used were identical to the original review that was published (Parks, R.M 2012). There were no set criteria that was used to define CGA in our methods, we excluded studies from our literature list if there was no form of CGA mentioned in the methodology of the study.
Comment 4: In the description of the Critical Appraisal in Methods, please include more explanation of the criteria used and a supporting reference or references.
Response 4: This section has been expanded upon, and the reference included.
Comment 5: Mention is missing of the following references, and others that are pertinent to this review, that included women with early-stage breast cancer:
Response 5: Thank you for highlighting reviews that could be useful to our systematic review. Having reviewed the recommendations, we have reviewed and included the applicable studies mentioned in our discussion. Unfortunately, it appears that some studies that were highlighted, did not come up during our initial searches conducted by our team, therefore we will not be able to add those studies to our final study list due to parameters of the systematic review.
Comment 6: There are several reports from CALGB 49907 and CALGB 369901 that would be pertinent to the discussion, including the following:
Response 6: These reports have been reviewed and referenced in the discussion.
Comment 7: Section 4.2 includes references to work related to advanced cancer (ex 15, 31, 32), not breast cancer, and seems disjointed. There is other work that is pertinent (see reference).
Response 7: Thank your for providing a list of studies. Those studies that might be relevant to our current study have been included. Reference 32 is used to provide further evidence of how CGA can be an effective tool to help determine factors influencing survival or mortality (further addressed in response 12).
Comment 8: On line 201, please specify which ‘biomarkers’ these are.
Response 8: This has now been specified. On the copy our team downloaded, this is on line 255 for reference.
Comment 9: The sentence on lines 202 and 203 seems out of place and the supporting reference is to a review paper.
Response 9: The review paper that is mentioned Okonji, D.O is proving a premise for the discussion, and not as supporting evidence to the discussion points being made. Further on in the section we expand on points with additional supporting evidence.
Comment 10: Reference 31, does not seem pertinent to extent of breast surgery and should be checked.
Response 10: We have reviewed the literature and have amended the reference to with an appropriate paper.
Comment 11: The sentence on line 207 pertains to renal cell carcinoma, but the reference 32 is about patients with lymphoma.
Response 11: This has been rectified with the correct reference.
Comment 12: How is the study of Stotter et al akin to the prior mentioned study? Were the tools similar? How was treatment decision-making affected?
Response 12: The overall treatment decision in Stotter et al and Pierantoni F et al were similar. Both studies conducted a pre-treatment and post-treatment CGA to categorise patients based on their frailty, and patients’ likelihood chance of survival post treatment. The use of comparison between the two studies, highlights how successful CGA is being used as a survival rate indicator in other cancer types, as well as in breast cancer. The comparison provides for further evidence indicating of the versatility of CGA, as well as providing further evidence of CGA being used in a breast cancer setting.
Comment 13: The summary on lines 212 and 213 is not well supported by the evidence provided.
Response 13: Amendments have been made, and additional evidence has been provided to support the section’s (4.3) conclusions.
Comment 14: Regarding the statement that the G8 is the most common screening tool (line 265), the qualifier should be included that there is the most literature about the G8. It may not be the most common tool, as is alluded to later in the paper.
Response 14: Thank you for bringing this to our attention. Please see the changes that have been made (line 308).
Comment 15: There are grammatical errors on the following lines: 30, 33, 44, 50, 60, 66, 69, 78, 104, 225, 244, 256, 283, and miss-spelled words in references.
Response 15: All grammatical errors have been reviewed and corrected. All spellings in references are the same spellings of that of the published titles of those references. There may be discrepancies between variations of English (UK) and English (US).
Reviewer 2 Report
The authors report a systematic review. They focus on the value of a comprehensive geriatric assessment in older women with primary breast cancer.
The review is well designed and well written. It updates an earlier review by the same group and reports on relevant new literature. It covers a medical field of growing importance, and reports clinically relevant findings.
Minor limitations:
In the abstract the authors refer to their prior review and mention the year 2012, in the introduction 2011 is reported.
At different parts of the manuscript the authors report, that they address older woman with primary breast cancer, at other part, they use the term early breast cancer.
Results section: (Table 1, Table 2) are mentioned, however figure 1 would fit better.
Results section: Content of table 1 is mentioned, however not table 2.
Figure 1: records after duplicate removed – I would suggest to mention the number of duplicates instead, as 491 is the number of records screened, which is mentioned in the next box.
3rd box right column: n=115 is mentioned twice.
Author Response
Comment 1: In the abstract the authors refer to their prior review and mention the year 2012, in the introduction 2011 is reported.
Response 1: This has been amended.
Comment 2: At different parts of the manuscript the authors report, that they address older woman with primary breast cancer, at other part, they use the term early breast cancer.
Response 2: If primary breast cancer is mentioned in the tables, for transparency we used the terms that was described by the original studies. We have changed the terms from primary breast cancer to early breast cancer.
Comment 3: Results section: (Table 1, Table 2) are mentioned, however figure 1 would fit better.
Response 3: Thank you, this has been amended.
Comment 4: Results section: Content of table 1 is mentioned, however not table 2.
Response 4: Thank you, this has been amended.
Comment 5: Figure 1: records after duplicate removed – I would suggest to mention the number of duplicates instead, as 491 is the number of records screened, which is mentioned in the next box.
Response 5: This has been changed to: “Duplicates identified”.
Comment 6: 3rd box right column: n=115 is mentioned twice.
Response 6: Comment has been removed.
