Small Cell Lung Cancer in the Course of Idiopathic Pulmonary Fibrosis—Case Report and Literature Review

Round 1

Reviewer 1 Report

 

In this report, a case of coexistence of IPF and small cell lung cancer in a 76-year-old patient was present. However, several main point should be noted as below.

1) The big disadvantage of this case report was that, as to the case “coexistence of IPF and small cell lung cancer ” had been reported by many other groups since 1990. It could be of less interesting for the readers and has less publishing value. For example,

①Long WQ, Tsuda T, Hiraoka K, Kido M.Four cases of lung cancer associated with idiopathic interstitial pneumonia. J UOEH. 1990 Jun 1;12(2):251-60.

②Kim EJ, Kim SR, Jin Gang S, Park SY, Han YM, Lee YC.Tonsillar metastasis of small cell lung cancer in a patient with idiopathic pulmonary fibrosis: a case report.Medicine (Baltimore). 2015 Feb;94(7):e565.

③Ide M, Tanaka K, Sunami S, Asoh T, Maeyama T, Tsuruta N, Nakanishi Y, Okamoto I.Durable response to nivolumab in a lung adenocarcinoma patient with idiopathic pulmonary fibrosis.Thorac Cancer. 2018 Nov;9(11):1519-1521.

④ Fukunaga K, Yokoe S, Kawashima S, Uchida Y, Nakagawa H, Nakano Y.Nintedanib prevented fibrosis progression and lung cancer growth in idiopathic pulmonary fibrosis.Respirol Case Rep. 2018 Sep 14;6(8):e00363.

⑤ Yamakawa H, Oba T, Ohta H, Tsukahara Y, Kida G, Tsumiyama E, Nishizawa T, Kawabe R, Sato S, Akasaka K, Amano M, Kuwano K, Matsushima H.Nintedanib allows retreatment with atezolizumab of combined non-small cell lung cancer/idiopathic pulmonary fibrosis after atezolizumab-induced pneumonitis: a case report.BMC Pulm Med. 2019 Aug 22;19(1):156

⑥Shiratori T, Tanaka H, Tabe C, Tsuchiya J, Ishioka Y, Itoga M, Taima K, Takanashi S, Tasaka S.Effect of nintedanib on non-small cell lung cancer in a patient with idiopathic pulmonary fibrosis: A case report and literature review.Thorac Cancer. 2020 Jun;11(6):1720-1723.

⑦Kai Y, Matsuda M, Fukuoka A, Hontsu S, Yamauchi M, Yoshikawa M, Muro S.

Remarkable response of non-small cell lung cancer to nintedanib treatment in a patient with idiopathic pulmonary fibrosis. Thorac Cancer. 2021 May;12(9):1457-1460.

⑧Zhang X, Li W, Li C, Zhang J, Su Z.Chemotherapy in idiopathic pulmonary fibrosis and small-cell lung cancer with poor lung function.BMC Pulm Med. 2021 Apr 15;21(1):122.

⑨Dabholkar S, Gao B, Chuong B.Nintedanib-A case of treating concurrent idiopathic pulmonary fibrosis and non-small cell lung cancer. Respirol Case Rep. 2022 Jan 12;10(2):e0902.

⑩Hasegawa M, Uehara A, Suzuki T, Sekine R, Yazawa M, Ichikawa D, Koike J, Shibagaki Y.Nintedanib-induced glomerular microangiopathy: a case report. CEN Case Rep. 2020 Nov;9(4):295-300.

2) The pathological and IHC images about IPF and small cell lung cancer in this case failed to be provided.

Overall, this paper was not qualified, it didn't fulfill the standards established for the journal to be considered for publication.

 

 

Author Response

Thank you very much for the prompt review. Based on your suggestion we added several positions of similar cases  to our discussion. Most of the cases you cited include non small cell lung cancer especially adenocarcinoma in wich nintedanib is commonly used in treatment. Small cell lung cancer is mentioned only in few of them that  is why in our opinion it is worth presenting. We broaden the discussion concerning innovative treatment including immunotherapy.

Regarding histopathological images, since in this case diagnosis was made on clinical and radiological features as it is often enough to make IPF diagnosis. In the case of our patient surgical biopsy was not performed due to underlying COPD.  We added this information in the discussion.

We hope that after changes, it will fulfill your expectation as a reader and reviewer.

Reviewer 2 Report

Dear authors, 

In figure 1 can you provide TAC images at the same layer depth? Panel A and B are quite similar, but different from panel C. I understand that panel see wants to make relevant the tumor image, however I feel important to have the over view at that depth at timepoint A and B and other way around. Maybe, showing to images at both layer depths for each time point it will make sense.

Any information or especulation regarding patient's evolution that can be included in the discussion section?

Author Response

Thank you for the remark regarding images depth.  Indeed Panel A nad B focus more on pulmonary tissue  and panel B resent changes on tumor size. We added more scans at each time point. 

As the patient continue treatment we added  description of further steps. We also expanded the discussion regarding future options. 

Reviewer 3 Report

The topic is interesting. However, there are issues with the case and it should be better described. A big issue is that I don't agree with the IPF diagnosis. Since the patient did not have a biopsy, the diagnosis of IPF would need to rely on a definite UIP pattern on HRCT, which is not present in this case because of the GGO in the upper parts of the lungs. To me, this sounds more like fibrotic NSIP... Also, what was the stage of the SCLC? Did the patient have a PET-CT? What happened after the two first cycles of chemotherapy? We need to know how many cycles the patient received, did he have toxicity, what was his PFS and OS?

I think radiation therapy and its risk with pulmonary fibrosis could be discussed more in details. Also, I don't agree with the comments made by the authors on immunotherapy saying that it is not a breakthrough in SCLC treatment. Yes, the benefit on survival is modest, but there is a high unmet need in SCLC patients and there are some very good and long time responders. We need better biomarkers to select patients, but this is definitely a new standard of care treatment and it is recommended by all guidelines as the best first line treatment in combination with chemotherapy.  It would be interesting to know why it was not given to the patient in this case, and also to include in the discussion a section on the risks of immunotherapy in patients with pulmonary fibrosis.

Author Response

Thank you very much for the constructive remarks. We provided more images to add more details to the IPF diagnosis. Although the diagnosis based on radiological patterns might always be a point to discussion in our option it is classic HRCT pattern including: honeycombing, which is the distinguishing feature , reticular abnormalities,  distribution: subpleural with a basal predominance and absence of features suggestive of an alternative diagnosis .

We added information about stage of small cell lung cancer which was based in CT scans , however PET CT was not performed. As the patient continue treatment we added description of further steps including toxicity and outcomes. We emphasized the importance of immunotherapy combination in SLCCL, however we have to realize the results are not as spectacular as in NSCL.  In the discussion we mentioned risk factors of pneumonitis and the use of checkpoint inhibitors in IPF.

Round 2

Reviewer 1 Report

This revision has answered my concern. No further Q. 

Reviewer 3 Report

Thank you for the corrections. All my comments have been addressed.

I have no additional comments, except that the sentence at line 210 is incomplete: In patients with poor lung function may lead to worse prognosis.