Dealing with stage IIIA N2 non small cell lung cancer (NSCLC)

Shobha Shukla and Bobby Ramakant, CNS (Citizen News Service)
Dr Francoise Mornex, Member, Board of
Directors, IASLC and APLCC 2016 Committee
The treatment of locally advanced Non Small Cell Lung Cancer (NSCLC) is becoming a significant challenge because of a growing proportion of patients with unresectable stage III disease. Despite a multimodality approach consisting in concurrent chemo-radiotherapy, the prognosis remains poor. “Before starting treatment, the stage IIIA or IIIB status of the patients need to be confirmed. They should have had their CT scan, brain MRI and PET scan done and, additionally, if possible, their N2 status must have been proven either by mediastinoscopy or by endobronchial or endo-esophagus ultrasound. This ensures that they do not have metastasis, their N2 status is known and the size of the tumour is in the stage IIIA or IIIB” said Dr Francoise Mornex, Professor of Oncology at the University Claude Bernard in Lyon, France.

She is also the Chairman of the Radiation Oncology Department in Lyon, Centre Hospitalier Lyon Sud, and member of Board of Directors of IASLC and APLCC 2016 Committee.

Investigative staging for mediastinal node is key

Dr Punnarerk Thongcharoen
Member, APLCC 2016 LOC
Agrees Dr Punnarerk Thongcharoen, a senior thoracic surgeon in Thailand’s oldest and largest hospital - Siriraj Hospital, Faculty of Medicine, Mahidol University - and member, APLCC 2016 Local Organizing Committee. “Just like other cancers, if lung cancer is diagnosed when the disease is in an early stage then there are more chances of cure with surgery. If it is an advanced case of lung cancer then chances of cure are less. Hence the first thing is to identify whether N2 lymph nodes are involved or not – only then we should progress ahead and manage patients properly. If it is N2 disease then we need to further classify if it is bulky N2 disease (advanced stage) or non-bulky N2 disease. For bulky N2 lung cancer, probably appropriate chemotherapy and radiation therapy might be a better option. For non-bulky lung cancer disease, surgery may still have a role. Usually we start with chemotherapy and radiotherapy first and then reassess if we are able to resect the tumour” said Dr Thongcharoen.

“Some physicians and surgeons are still relying on non-invasive staging approach like CT scan or PET scan. We should encourage treating doctors to get the status confirmed whether it is N2 disease or not. So the key is to do investigative staging for mediastinal node. We also need to train more doctors to be able to do these investigative staging procedures well and encourage all healthcare professionals to stay updated with the latest guidelines in lung cancer management,” he said.

Do not lose hope if NSCLC is unresectable!

The focus of Dr Mornex is specifically on those patients of stage IIIA N2 NSCLC who are unresectable (cannot be operated upon) because either their tumour is too big to be surgically removed or they are inoperable because of their local conditions due to comorbidities. Most of these are fragile and old patients—their median age is 71 years and they suffer from a lot of comorbidities, because of their age and also because many of them are smokers.

Dr Mornex explained that “The current treatment regimen for these patients is concurrent chemo-radiation. But unfortunately less than 50% of them are able to tolerate this regimen because of their advanced age and comorbidities. For patients who cannot be treated with concurrent chemo-radiation, mostly induction chemotherapy, followed by full dose of radiation, is done. This is called a sequential treatment - chemotherapy followed by radiation”.

“In those less than 50% of the patients who can be put on concurrent chemo-radiation, there is a choice of several drugs. Most of the time we use a doublet - meaning 2 agents of chemotherapy - one of which usually is cisplatin, if the patient is less than 70-75 years old, and this can be joined with another drug like Vinorelbine, VP16, gemcitabine, or taxol. In case the patients are fragile or of age 70-75 years or more, we will use carboplatin instead of cisplatin. So, if the patient’s condition permits, we mostly use two agents of chemotherapy - one of them being a platinum agent. Regarding radiation, there is still a question mark on what radiation dose is appropriate to be delivered. But based on the results of a large randomised controlled study called RTOG 0617 that were presented in 2015, a lower dose of standard radiation of 60 Gray (Gy) gave better outcome in terms of median survival when compared to the high dose radiation. So the current recommendations are to combine 2 agents of chemotherapy - and 60 Gy of radiation”, said Dr Mornex.

What radiation technique should be used?

“There is a choice of using either the technique of 3D conformal therapy or Intensity Modulated Radiation Therapy (IMRT). Dr Mornex informed that, “In the RTOG 0617 trial, 47% of the patients received IMRT technique that gave better results, even though the tumours on which it was used were larger compared with those on whom conformal 3D therapy was used. Moreover IMRT has shown to also better protect the normal organs, especially the heart. So now for patients of stage IIIA N2 of NSCL cancer we should use 2agents of chemotherapy, 60 Gy of radiation and, if possible, IMRT technique for radiotherapy.”

The way forward

The question for this stage of lung cancer is to know how to integrate correct systemic adjuvants, and more specifically, the targeted therapy and immunotherapy. “We have some trials combining targeted agents and concurrent chemo radiation, or trials introducing targeted adjuvants before concurrent chemo radiation or after chemo radiation. We have tried GKI, Erlotinib, Gefitinib and Cetuximab. But so far, for tyrosine kinase inhibitor (TKI) therapy, none of these agents, when used with concurrent chemo radiation, have helped in improving the results.”

Added Dr Mornex: “There are several ongoing trials with new agents that might hopefully improve the results. Some of these trials are dedicated to Asia, because Asian patients do not have the same mutations as European or American patients. It will be extremely important to compare the results of the same trial designed in Asia with those in other parts of the world, because it is important to have responses of different tumours and a precise tolerance profile to these new agents, especially when combined with radiation.”

Changing scenario

Dr Mornex shared that, “Now we are observing more nonsmoking and young patients with this type of cancer - something which I did not see 20 years ago in my clinical practice. Obviously there are some changes in the chromosomes, and we are not sure about the factors which are affecting the genes in the mutations of our patients. It has not yet been possible to show whether or not this cancer in young patients or in nonsmokers will be different in terms of outcomes for the same cancer in smoking patients. But the good news is that for these patients we can identify if they have some known mutations or not and if they have this mutation we can propose to them very specific treatments with good outcomes. So we will be able to personalise the treatment that we are offering to our patients and by this way also we should be able to improve the survival. One of the big questions will be to know how to combine the new agents (which are driven by the mutations of the patients) with chemo radiation to improve results without increasing toxicity. I think with the new agents and the combination of the new agents and the recent radiotherapy treatments we should be able to dramatically improve the results for this disease in a near future. Targeted therapies and immunotherapy are likely improve the management of locally advanced NSCLC in the future.”

Shobha Shukla and Bobby Ramakant, CNS (Citizen News Service)
14 May 2016