Papillary, acinar etc types and behaviour differences - 1294315

There is ongoing work on finding the best prognostic markers for lung adenocarcinoma. Below is a paragraph from an introduction of a 2015 publicly available paper that describes the utility of histology for prognosis.

Lepidic gives the best prognosis, while acinar/papillary have intermediate prognosis, with solid/micropapillary giving the worst. As an aside, lepidic is generally associated with the non-invasive part of a ggo, and the word solid on histology has not the same meaning as 'solid' on a ct scan.

"Mitosis Trumps T Stage and Proposed International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification for Prognostic Value in Resected Stage 1 Lung Adenocarcinoma"

There is now evidence that adenocarcinoma histologic architecture is of prognostic value,3–5 in particular that lepidic-predominant tumors have superior survival to those with a solid or micropapillary pattern and that acinar or papillary subtypes have an intermediate prognosis.5 In 2011, the International Association for the Study of Lung Cancer (IASLC), together with the American Thoracic Society and the European Respiratory Society, proposed a multidisciplinary classification for lung adenocarcinoma based on histopathologic architectural subtypes.6 Since then, additional studies have validated the reproducibility and prognostic value of the classification in independent series,5–13 although its value in more advanced stages of disease remains in doubt.14,15 In an effort to define comprehensive pathologic prognostic marker sets, the prognostic value of pathologic characteristics other than architecture is increasingly under evaluation. There is evidence that mitotic count16,17 and Ki-67 labeling18 have value in predicting recurrence of stage 1 adenocarcinoma and that nuclear area and major dimension are independent prognostic markers.19

https://www.sciencedirect.com/science/article/pii/S1556086415323704

These studies will/are providing oncologists more specific info on the populations most likely to benefit from adjuvant therapy (chemo after surgery, it's toxicities need to be weighed against benefits). If your cancer is more likely to recur, it may be worth the chancing toxicities of adjuvant treatment to be cured.

I hope you are doing well,
Janine

After several years of thinking about this, I think I have finally understood in a simple way why adjuvant therapy is helpful at higher stages (II and III) but not at the lowest stage 1 [with some exceptions, which I get to later].

The first part is that higher stages are more likely to have hidden metastatic cancer so despite thinking you got it all in surgery, you really didn't.

The second part is there is an increased risk of early death just from the chemotherapy itself. I read a 2018 paper about a large database that found, retrospectively, the absolute mortality rate 6 months after starting adjuvant chemo was about 4%. So if the absolute long term benefit were less than 4% then the net long term benefit is negative because you already lost the 4% in the short term. I'm a bit puzzled that this paper didn't compare the mortality rate to those who didn't get chemo and therefore would die in the short term but I guess that number is small. I hope this makes sense.

A second issue is that gene panel arrays are starting to be studied instead of stage, and standard pathology features to categorize high risk [according to NCCN guidelines]. High risk are those that are more likely to have hidden metastatic cancer and therefore benefit from chemo.

There was a very recent paper on that too. This paper claimed that there size 14 array of gene markers did a better job separating those that benefit from chemo from those that don't than the current, standard, method following NCCN guidelines. I I can look up to find these papers again if someone wants to look at them.

The publicly available 2018 paper on the gene array I referred to is: https://www.clinical-lung-cancer.com/article/S1525-7304(17)30150-X/full…

This prospective, nonrandomized study provides initial evidence that high-risk designation according to the 14-gene prognostic assay also predicts benefit from adjuvant chemotherapy for very early stage NSCLC, and further supports the superiority of molecular stratification over current NCCN criteria at identifying high-risk patients.

Estimated 5-year DFS was 48.9% among molecular high-risk patients who did not undertake adjuvant chemotherapy, 93.8% among untreated molecular low-risk patients, and 91.7% in molecular high-risk patients who did undergo chemotherapy (P = .004). In contrast, DFS was only 75.2% in untreated NCCN low-risk patients, and 61.9% in untreated NCCN high-risk patients (P = .183).

There's a 2018 paper on early mortality in adjuvant chemotherapy but it is behind a subscription wall. The summary is here: https://www.sciencedirect.com/science/article/pii/S1556086418300364

The National Cancer Database was queried for patients age 18 or older in whom stage IB to IIIA NSCLC had been diagnosed between 2004 and 2012 and who had received multiagent adjuvant chemotherapy starting within 120 days from the surgical resection with negative surgical margins. Age groups were divided as follows: younger than 50, 51 to 60, 61 to 70, 71 to 80, and older than 80 years.

Results
A total of 19,691 patients met the eligibility criteria, 19,398 of whom had a known 6-month mortality status. The median age was 65 years (range 19–89). The 1-, 2-, 3-, 4-, 5-, and 6-month cumulative mortality rates from initiation of chemotherapy were 0.7%, 1.3%, 1.9%, 2.6%, 3.2%, and 4.1% respectively.