Vulnerability in Colorectal Cancer: Adjusted Gross Income and Geography as Factors in Determining Overall Survival in Colorectal Cancer: A Single-Center Study Across a Broad Income Inequality in an American Context
Round 1
Reviewer 1 Report
Comments and Suggestions for Authors
see attached review; major issues are italicized
Comments for author File: 
Comments.pdf
Comments on the Quality of English Language
minor issue
Author Response
10/31/2024
Current Oncology (ISSN 1718-7729)
Manuscript ID: currooncol-3229749
Re: Point-by-point replay to the Reviewer 2 comments/questions
Dear Sir or Madame:
Thank you very much for your very valuable comments. Please see below our answers:
- Comment/question n.1: ”…Page 2 and Table 1 - Insurance status is reported as "private or Medicare vs. Medicaid vs. not insured". This appears to be a heavily insured population and that variable would be expected to have a correlation with SES as well as a strong and potentially independent influence on CRC stage at diagnosis and overall survival (at a minimum), yet none of the subsequent analyses reported in Tables 2-5 seem to reference insurance again. It would be appropriate to include it, and possibly adjust for it in some way, in all analyses and inferences. How those data were analyzed should also be explained in the methods section…”
Answer to comment/question n.1 We have now included both insurance and treatment type received in our analyses. Please, see Tables 1, 3, 4, and 5.
- Comment/question n.2: ”…Conclusion - In the final sentence, the authors make an impassioned plea to direct additional federal and state resources to 'community cancer centers" to support research, screening, and treatment of people of any SES diagnosed with cancer. While that would be a potentially impactful action, it is far too narrow of a recommendation, as many community cancer centers don't offer cancer screening or preventive services, but only care for diagnosed cancer patients (and often, only those that have suitable insurance or the ability to self-pay). For that reason, the plea should be broadened significantly beyond community cancer centers to include primary care services, cancer screening services, cancer treatment services, and supportive care services wherever they are offered to uninsured and low SES populations...most notably, in safety net health settings, community health centers, FQHCs, etc…”
Answer to comment/question n.2 On lines 339 to 340 we edited the text as follow: “…Therefore, more Federal and State resources should be programmatically directed to community cancer centers, and any other agency that supports research, screening, and treatment of people of low SES diagnosed with CRC.…”
Thank you very much, again for providing your comments/questions and for allowing us to improve our manuscript.
Sincerely,
The Authors of “Vulnerability in Colorectal Cancer: Adjusted Gross Income And Geography as Factors in Determining Overall Survival in Colorectal Cancer. A Single Center Study in a Widespread Income Inequality American Geography”
Reviewer 2 Report
Comments and Suggestions for Authors
Thanks for the opportunity to review the work by Doria, et al. The study involves a small observational study of the association between AGI, geography, and CRC overall survival in a small area of central New Jersey. The authors report several strong associations between race and age at diagnosis, race and SES, stage at diagnosis and SES, overall survival and SES. The work was thoughtfully conducted and the results are reasonably documented. However, attention to a couple of issues would strengthen the manuscript further.
Questions/recommendations:
1. Page 2 and Table 1 - Insurance status is reported as "private or Medicare vs. Medicaid vs. not insured". This appears to be a heavily insured population and that variable would be expected to have a correlation with SES as well as a strong and potentially independent influence on CRC stage at diagnosis and overall survival (at a minimum), yet none of the subsequent analyses reported in Tables 2-5 seem to reference insurance again. It would be appropriate to include it, and possibly adjust for it in some way, in all analyses and inferences. How those data were analyzed should also be explained in the methods section.
2. Conclusion - In the final sentence, the authors make an impassioned plea to direct additional federal and state resources to 'community cancer centers" to support research, screening, and treatment of people of any SES diagnosed with cancer. While that would be a potentially impactful action, it is far too narrow of a recommendation, as many community cancer centers don't offer cancer screening or preventive services, but only care for diagnosed cancer patients (and often, only those that have suitable insurance or the ability to self-pay). For that reason, the plea should be broadened significantly beyond community cancer centers to include primary care services, cancer screening services, cancer treatment services, and supportive care services wherever they are offered to uninsured and low SES populations...most notably, in safety net health settings, community health centers, FQHCs, etc.
Author Response
10/31/2024
Current Oncology (ISSN 1718-7729)
Manuscript ID: currooncol-3229749
Re: Point-by-point replay to the Reviewer 1 comments/questions
Dear Sir or Madame:
Thank you very much for your very valuable comments. Please see below our answers:
- Comment/question n.1: ”…Similarly, whites were diagnosed later in life (70.9 years of age) compared to non-whites (p = 0.001), but paradoxically, this did not lead to a significant difference in OS (p = 0.56).” o Add the age of the non-whites…”
Answer to comment/question n.1 We added the required data: “…Whites were diagnosed later in life (70.9 years of age) compared to non-whites Black (66.5), Asian (61.7), Hispanic (58.5) (p = 0.001)…” See line 26 to 27.
- Comment/question n.2: ”…Is this “paradoxical” – earlier onset of cancer in non-Caucasians has been described (see below)…”
Answer to comment/question n.2 We are unclear on what the Reviewer is asking. We will be more than happy to address this question if it can be reformulated. Please, let us know. Thank you.
- Comment/question n.3: ”…Stage at diagnosis was a significant predictor of OS, when it pertained to SES (p = 0.008). o How could there be a progressive decreased risk for achieving longer OS with living in an area of higher SES compared to lower. The pts are diagnosed at a stage of more advanced disease with lower SES, so how is OS lower with high SES? And Kaplan-Meier curve more favorable for higher SES. â–ª From text: Kaplan–Meier analysis showed OS being significant better in the higher SES (p = 0.017) group [Figure 1]…”
Answer to comment/question n.3 We apologize for the confusion. Fig 1 plots the chances of survival beyond a specific time point. As such, a higher curve implies lower risk of dying. This is consistent with the reviewer’s expectation that patients with Low SES are diagnosed at a more advanced stage than those from High SES and should have lower OS.
- Comment/question n.4: ”…Why did they choose year 2017 for income when the study ranged from 2000-2019? o This is a long time period and could substantial changes occur over that period?...”
Answer to comment/question n.3 There was an error in the original submission regarding the data year. The data were from 2015, not 2017 as initially stated. In the revised paper, we clarify that financial data by ZIP code were only available for the years 2011-2019. During this period, no significant changes in socioeconomic status (SES) were observed in most of the areas of interest. Therefore, we originally chose to use data from the midpoint of the available time range. However, after revising the analyses, we have now used data from 2011, the midpoint of the study time, which we believe now to be more appropriate to represent the SES for the entire 2000-2019 period. We appreciate the reviewer for highlighting this issue. The related text has been modified/added as follow: “…We extracted data from individual income tax returns, focusing on selected income and tax items by state, ZIP code, and adjusted gross income (AGI) for tax years 2011 to 2019 for the 21 ZIP codes for Mercer County, NJ. AGI information by ZIP code was unavailable on the Census website (https://data.census.gov) because it was not reported prior to 2011. Socioeconomic status (SES) appeared stable over the 10-year period, with only 5 out of 21 ZIP codes (08618, 08611, 08619, 08560, and 08501) experiencing changes. These shifts affected the SES classification of 407 patients: 325 moved from mid-low to low SES, 61 moved from mid-high to mid-low SES, and 21 moved from high to mid-high SES. Our analyses, performed on data from each of these years, yielded virtually identical results in both qualitative and quantitative terms, as there was no substantial distinction between the two lowest SES categories, where the biggest shift occurred. Given that clinical and hospital data were collected for patients treated between 2000 and 2019, and that the financial data analyses for 2011-2019 showed no significant differences, we decided to use the SES designations based on the data from the 2011 tax year. This approach reasonably assumes that, similarly to the period 2011-2019, minimal SES changes occurred between 2000 and 2010, and that 2011 SES data adequately represent the entire study period…” Please, see lines 146 to 161.
- Comment/question n.5: ” … Don’t need to include every item recorded in table 1 in the second sentence…”
Answer to comment/question n.5 We deleted the redundant text from the manuscript. Please, see deleted text lines 195-199
- Comment/question n.6: ” … Table 1 which is “demographics” in parentheses? o Do we need the â–ª race section as have race/ethnicity section â–ª Hispanic section as get the Hispanic proportion from race/ethnicity section o change average age or subject to average age at diagnosis o Explain SES and categories under chart”
Answer to comment/question n.6 We thank the reviewer for the comments that help make the table clearer. We have made all the suggested changes. Please, see revised Table n. 1 .
- Comment/question n.7: ” … Paragraph 1 – avoid discussion in results rather than Discussion section o commentary belongs in discussion â–ª “making our analysis more relevant 152 to our geography and allowing us to target specific interventions…”
Answer to comment/question n.7 The following text has been moved to the discussion section of the manuscript: “…Our data suggest that OS in patients with CRC is in part attributable to the Zip Code and its associated SES; race or ethnicity did not seem to be associated with overall survival, prompting the premise, that geography (Zip Code) and its associated income level form major determinants in OS after being diagnosed with CRC. Others have also recognized the importance of social determinants of health in CRC (11).. Our service area includes both urban and suburban population; of note our sample is different from a nationwide sample (US) as it includes >35% non-whites making our analysis more relevant to our geography and allowing us to target specific interventions…” Please, see lines 273 - 282
- Comment/question n.8: ” … “Lives and resides” redundant…”
Answer to comment/question n.8 Sentence was revised. Please, see line 104
- Comment/question n.9: ” … Is this more methodology and not a result? â–ª “Using the patients’ zip code and tax return data associated with the zip code, we can derive the socioeconomic status (SES) of the area where the patient lives and resides…”
Answer to comment/question n.9 Text has been moved Please, see line 102 - 104
- Comment/question n.10: ”…“indicating widespread income inequality.” • Rather than “widespread” do the authors mean “a large” income gap between the highest and lowest zip codes…”
Answer to comment/question n.10: This was edited into: “…large income gap between the highest and the lowest zip codes…” Please, see lines 208 - 209
- Comment/question n.11: ”… Change first sentence to “as expected, stage at diagnosis…”
Answer to comment/question n.11: Sentence was revised per reviewer’s recommendation. Please, see line 211
- Comment/question n.12: ”… Would drop the “interesting paradox” and just report the data. Colon cancer developing at younger age in non-Caucasians has been observed…”
Answer to comment/question n.12: Sentence revised. Please, see line 216
- Comment/question n.13: ”… Would say that there was significant variation in age of diagnosis between the groups…”
Answer to comment/question n.12: This has been addressed as follow: “…that Caucasians were diagnosed at a later age (70.9 ± 14.1 years of age) compared to non-Caucasians (Black 66.5 ± 13.7, Asian 61.7 ± 10.9, Hispanic 58.5 ± 14.9 years of age) which was significantly different from each other (p = 0.001, ANOVA)…” Please, see lines 216 - 219
- Comment/question n.14: ”… Maybe compare Caucasian vs. Non-Caucasian and report here as well (don’t need to add to table 3)…”
Answer to comment/question n.14: Unfortunately, this would not be prudent in this particular case. In fact, from table 5, the only racial group differentiated from the Caucasian group is the Asian. As such lumping the three non-Caucasian groups (Blacks, Hispanics, and Asians) would lead into potential misleading conclusions as any differentiation between these groups could be solely driven by the Asian group, but it would imply a difference between Caucasians and the other minority groups as well.
- Comment/question n.15: ”… Majority of Whites lived in mid-high and high (not high), and the vast majority of Black and Hispanic patients resided in low and mid-low…”
Answer to comment/question n.15: Sentence has been revised as follow: “…majority of the white population living in an area of mid-high and high SES and the vast majority of the Black and Hispanic patients residing in low-or mid low SES zip codes... “ Please, see lines 224 - 226
- Comment/question n.16: ”… Sentence 1 is too long – please simplify or 2 sentences…”
Answer to comment/question n.16: We now have two sentences that hopefully make the information clearer. Please, see lines 230 - 236
- Comment/question n.17: ”… Don’t repeat results from table 3 – maybe add table 3 results to para 2…”
Answer to comment/question n.17: This is a great point and we thank the reviewer for pointing it out. We have now moved the following sentence in paragraph 2: “…In our analysis, race or ethnicity was not immediately associated with OS despite having a differential distribution in our sample [Table 3]…” Please, see lines 220 - 222
- Comment/question n.18: ”… Table 5 and related discussion – all of the following â–ª Confusing. Should this table be titled “Overall Survival (OS): Multifactorial Regression Analysis” • Perhaps take refs out of title and asterisk the parameters and include reference/comparator under table o Stage 0 o Race Caucasian o SES Low o What is the comparator or reference for age?...”
Answer to comment/question n.18: We made the suggested changes to the table and we added the reference group for the insurance. There is no need for a reference group for age as this is a numerical (continuous) variable and the risk is interpreted as per unit increase in the variable, i.e., per each year increase in the age at diagnosis.
- Comment/question n.19: ”…So this finds OS no different by race/ethnicity with multifactorial analysis? Were all the right factors considered?...”
Answer to comment/question n.19: That is correct. Since race is highly associated with several factors already included in the model, such as SES and access to insurance, our analyses point to that, once these factors are accounted for, there is no residual effect of race.
We have incorporated several relevant factors identified in the literature. While other factors may influence overall survival (OS), the existing variables have rendered the effect of race insignificant. Therefore, it is highly unlikely that adding additional factors would make the effect of race significant. In fact, including additional factors, potentially associated with race, would further reduce the contribution of race in the OS as they will be stripping away parts of the residual effect explained by race.
- Comment/question n.20: ”… Given the age of diagnosis is lower in non-Caucasians (table 3), might expect younger age of diagnosis in lower SES zip codes more heavily weighted with non-Caucasians – but did not see this (table 4). Is the diagnosis of CRC therefore delayed here, and is that why the % of advanced cancer is higher and OS is lower?...”
Answer to comment/question n.20: With the new data adjustment (year 2011), there is now a trend with lower SES being younger as the Reviewer expected. Even in the previous analysis, the trend was still there but without statistical significance. However, there is no relationship between stage of cancer and race or SES (p= .325 and .066, respectively). As such it doesn’t appear to be the case that delayed diagnosis might contribute to differences in the OS between the different SES groups.
- Comment/question n.21: ”… Does this analysis answer the question of whether the OS is more greatly impacted by SES in Blacks and Hispanics vs. Whites?
Answer to comment/question n.21: This question can be answered via the use of interaction term between race and SES in the Cox PH model. We have performed the analysis, but we found no evidence at all of interaction between the two factors. In concluding, the data do not provide any evidence that OS is more greatly impacted by SES in Blacks and Hispanics vs. Whites.
- Comment/question n.22: ”… Would remove discussion here as well and move it to the discussion section…”
Answer to comment/question n.22:The following text was edited:”… Our data suggest that OS in patients with CRC is in part attributable to the Zip Code and its associated SES; race or ethnicity did not seem to be associated with overall survival, prompting the premise, that geography (Zip Code) and its associated income level form major determinants in OS after being diagnosed with CRC. Others have also recognized the importance of social determinants of health in CRC (11)and moved from the section of the manuscript labeled “Results” to the Discussion. Please, see lines 273 - 278
- Comment/question n.23: ”… - SES is the “only determinant we identified” - This paragraph needs a lot of tightening. The message is low SES is associated with higher risk for poorer OS with CRC. Later diagnosis. Greater Black and Hispanic representation. Why…”
Answer to comment/question n.23: We changed that paragraph as follow: “…The results of our study support the notion that low SES is associated with higher risk of poorer OS with CRC and later diagnosis…” Please, see lines 300 - 301
- Comment/question n.24: ”… Access to health care? Insurance, ?English as second language, low education, health literacy, fewer health care facilities, need for navigation, inability to lose time from work, and on and on o Nutrition as pointed out o ?obesity and other illnesses related…”
Answer to comment/question n.24: We noted your concerns, and we acknowledge that these can all be important factors. Regarding the insurance question: Insurance doesn’t seem to be the cause, we essentially had very few people that were not insured by medicare/private insurance (154 – 12%).
- Comment/question n.25: ”… How does the first recommendation stem directly this study?...”
Answer to comment/question n.25: We think that community-embedded health care workers such as Nurse navigator can bridge some of the most important gaps in the low SES zip codes. As an example, they could educate people about the importance of screening colonoscopy in preventing CRC. This is addressed in the manuscript.Please, see lines 321 - 329
- Comment/question n.26: ”… Agree with targeting zip codes based on SES. Then, what do you do about it?...”
Answer to comment/question n.26: We believe that working with the known vulnerable population (people residing in low SES zip codes) on bridging the postulated gaps might increase the rate of screening colonoscopies and decrease the incidence of late diagnosed CRC. This is addressed in the manuscript. Please, see lines 321 - 332
- Comment/question n.27: ”… Agree with all measures that have been shown to improve screening and access in low SES areas…”
Answer to comment/question n.27: Thank you for agreeing with us.
- Comment/question n.27: ”… Is there a need especially target non-Caucasians in low SES zips?...”
Answer to comment/question n.27: The result of our analysis supports the notion that people residing in low SES zip codes, irrespective of their race, are at higher risk of developing CRC because they are uniformly affected by similar hurdles. We believe that this finding represents the uniqueness of our study.
Thank you very much, again for providing your comments/questions and for allowing us to improve our manuscript.
Sincerely,
The Authors of “Vulnerability in Colorectal Cancer: Adjusted Gross Income And Geography as Factors in Determining Overall Survival in Colorectal Cancer. A Single Center Study in a Widespread Income Inequality American Geography”
Round 2
Reviewer 2 Report
Comments and Suggestions for Authors
The most important issues have been sufficiently addressed by the authors. Thanks for the revised manuscript. The remaining question re: a statement that is labeled as a paradox is that the issue is truly not a paradox, so that phrasing should be simply removed.
Thanks.
Author Response
11/6/2024
Current Oncology (ISSN 1718-7729)
Manuscript ID: currooncol-3229749
Re: Point-by-point replay to the Reviewer comments/questions
Dear Sir or Madame:
Thank you very much for your very valuable comments. Please see below our answers:
- Comment/question n.1: ”… The most important issues have been sufficiently addressed by the authors. Thanks for the revised manuscript. The remaining question re: a statement that is labeled as a paradox is that the issue is truly not a paradox, so that phrasing should be simply removed…”
Answer to comment/question n.1 We remove the words paradox and paradoxically from the manuscript, please see lines 27 and 216.
Thank you very much, again for providing your comments/questions and for allowing us to improve our manuscript.
Sincerely,
The Authors of “Vulnerability in Colorectal Cancer: Adjusted Gross Income And Geography as Factors in Determining Overall Survival in Colorectal Cancer. A Single Center Study in a Widespread Income Inequality American Geography”
