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Upfront Therapy Approaches in Gastric/GEJ Cancer

Insights From: Yelena Y. Janjigian, MD, Memorial Sloan Kettering Cancer Center; Alan P. Venook, MD, University of California San Francisco; Zev A. Wainberg, MD, UCLA School of Medicine
Published: Friday, Jan 05, 2018



Transcript: 

Yelena Y. Janjigian, MD: For patients with locally advanced nonmetastatic esophageal and stomach cancer, the multidisciplinary approach between pathology, surgery, radiation, oncology, radiology, and medical oncology team members is crucial. The first decision tree is, is this disease curable? And a careful review of the radiology and pathology is very important to determine the treatment plan.

For patients with localized disease who present with symptoms and a radiographically visible tumor, in the majority of the cases, surgery alone is insufficient to cure a patient. Therefore, a medical oncologist really becomes the coordinator of the team, to help improve chances of cure and to really get these patients through an operation, ultimately with help of all the team members. That will cure them. Patients who undergo surgery first may undergo a suboptimal resection that is not R0, which means it’s not a complete resection, and then you’re really wasting an opportunity to potentially cure this patient. After the surgery, the patients are usually nutritionally compromised and quite frail, and are no longer able to receive chemotherapy or chemoradiation treatments that could have augmented their response and success of the surgery from the beginning.

That’s why it’s very important to sit down together, take even 15 to 20 minutes. It doesn’t take very long, but look at the images together and figure out what the plan is here as opposed to trying to piecemeal it together later on.

For metastatic disease, chemotherapy is the most important treatment, and for a majority of the patients, the disease becomes a chronic illness. In these situations, radiation and surgery become a way to help improve their quality of life or palliate some of the symptoms. But chemotherapy is important. Increasingly with the use of immunotherapy and other targeted agents, we’ve used radiation therapy, focal ablation, to help augment the immune response to the tumor. It was systemic therapy, but this is more of a research tool at the moment.

Zev A. Wainberg, MD: When we evaluate patients with gastric and gastroesophageal junction cancers, we do try to take a multidisciplinary approach because we recognize that in the absence of metastatic disease, those patients will need a combination of chemotherapy; radiation therapy very often, which is provided by the radiation oncologists; and sometimes surgery, if it’s appropriate. So, it is a disease that is well served by a multidisciplinary approach. There are many mechanisms to do that, obviously, but one of the better ways is usually to discuss these patients in a tumor board setting where all the disciplines are represented. For patients who do not have metastatic disease and have treatment for curative intent, the goal would be to involve, in some way, shape, or form, all of those modalities in the treatment of the patient.

Alan P. Venook, MD: Patients with locally advanced stomach or GE junction cancer can be cured. The challenge is, how do you do that? What’s the best order in which to do the treatments? Combinations of chemotherapy, radiation, and surgery, or mixing and matching of all of those, may be the standards. Certainly, in Europe, the standard is chemotherapy followed by surgery. In the United States, more of a standard would be surgery followed by chemotherapy and radiation. And then, there are variations on that theme.

But the goal is to cure the disease. You achieve that infrequently, but you do achieve it occasionally. In Asia, you might achieve it more commonly because biologically, we think gastric cancer is different in Asia than in the West. But here, with combination therapy, the goal is to cure the disease. It probably happens in 15% to 20% of patients.

Zev A. Wainberg, MD: The optimal chemotherapy regimen for adjuvant and neoadjuvant therapy in gastric and GEJ cancers is quite controversial. It’s very different depending on where you treat patients, in the United States versus Europe versus Asia. I think, generally speaking though, most of the data support neoadjuvant use for patients who are at least T3 N0 or above, which are patients who may not be fully resectable. So, they’re not fully resectable, which is the majority of patients with gastric and GEJ cancers. Often now with those patients, the data support neoadjuvant treatment in gastric cancer, usually neoadjuvant chemotherapy alone in newer regimens such as the FLOT regimen, which has shown improved survival outcomes compared to the older regimens like ECF.

In the case of GE junction adenocarcinoma, where there’s a role for radiation, most of the data would support neoadjuvant chemoradiation with the CROSS study regimen, which is fractionated radiation along with carboplatin and Taxol [paclitaxel] given weekly. Those are some of the main elements. I think if you have a situation where therapy is not given neoadjuvantly and then the patient is found to meet criteria for adjuvant therapy, there’s support to do that as well, obviously after surgery. But I think while looking at the trend over the last 10 or 15 years in these diseases, it has been to move more of the treatment to neoadjuvant as opposed to adjuvant.

The role of radiation and chemoradiation in neoadjuvant gastroesophageal junction is well demonstrated in regimens like the CROSS regimen, where the role of chemoradiation is important because some of the tumor may involve the gastroesophageal junction. However, in the stomach tumors like gastric cancer, the role of radiation is much more controversial. And recent studies, such as the CRITICS study, have suggested that there may not be much benefit to giving adjuvant radiation in some of those patients. We’re waiting for more studies that are ongoing now, such as TOPGEAR or ARTIST-2, that will further clarify the role of radiation in gastric cancer. But at this point in time, the only data we have for adjuvant in gastric cancer for radiation are relatively old data from the intergroup study, where there still was a role for chemoradiation in the adjuvant setting. It’s much more controversial as opposed to GEJ.

Transcript Edited for Clarity 
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Transcript: 

Yelena Y. Janjigian, MD: For patients with locally advanced nonmetastatic esophageal and stomach cancer, the multidisciplinary approach between pathology, surgery, radiation, oncology, radiology, and medical oncology team members is crucial. The first decision tree is, is this disease curable? And a careful review of the radiology and pathology is very important to determine the treatment plan.

For patients with localized disease who present with symptoms and a radiographically visible tumor, in the majority of the cases, surgery alone is insufficient to cure a patient. Therefore, a medical oncologist really becomes the coordinator of the team, to help improve chances of cure and to really get these patients through an operation, ultimately with help of all the team members. That will cure them. Patients who undergo surgery first may undergo a suboptimal resection that is not R0, which means it’s not a complete resection, and then you’re really wasting an opportunity to potentially cure this patient. After the surgery, the patients are usually nutritionally compromised and quite frail, and are no longer able to receive chemotherapy or chemoradiation treatments that could have augmented their response and success of the surgery from the beginning.

That’s why it’s very important to sit down together, take even 15 to 20 minutes. It doesn’t take very long, but look at the images together and figure out what the plan is here as opposed to trying to piecemeal it together later on.

For metastatic disease, chemotherapy is the most important treatment, and for a majority of the patients, the disease becomes a chronic illness. In these situations, radiation and surgery become a way to help improve their quality of life or palliate some of the symptoms. But chemotherapy is important. Increasingly with the use of immunotherapy and other targeted agents, we’ve used radiation therapy, focal ablation, to help augment the immune response to the tumor. It was systemic therapy, but this is more of a research tool at the moment.

Zev A. Wainberg, MD: When we evaluate patients with gastric and gastroesophageal junction cancers, we do try to take a multidisciplinary approach because we recognize that in the absence of metastatic disease, those patients will need a combination of chemotherapy; radiation therapy very often, which is provided by the radiation oncologists; and sometimes surgery, if it’s appropriate. So, it is a disease that is well served by a multidisciplinary approach. There are many mechanisms to do that, obviously, but one of the better ways is usually to discuss these patients in a tumor board setting where all the disciplines are represented. For patients who do not have metastatic disease and have treatment for curative intent, the goal would be to involve, in some way, shape, or form, all of those modalities in the treatment of the patient.

Alan P. Venook, MD: Patients with locally advanced stomach or GE junction cancer can be cured. The challenge is, how do you do that? What’s the best order in which to do the treatments? Combinations of chemotherapy, radiation, and surgery, or mixing and matching of all of those, may be the standards. Certainly, in Europe, the standard is chemotherapy followed by surgery. In the United States, more of a standard would be surgery followed by chemotherapy and radiation. And then, there are variations on that theme.

But the goal is to cure the disease. You achieve that infrequently, but you do achieve it occasionally. In Asia, you might achieve it more commonly because biologically, we think gastric cancer is different in Asia than in the West. But here, with combination therapy, the goal is to cure the disease. It probably happens in 15% to 20% of patients.

Zev A. Wainberg, MD: The optimal chemotherapy regimen for adjuvant and neoadjuvant therapy in gastric and GEJ cancers is quite controversial. It’s very different depending on where you treat patients, in the United States versus Europe versus Asia. I think, generally speaking though, most of the data support neoadjuvant use for patients who are at least T3 N0 or above, which are patients who may not be fully resectable. So, they’re not fully resectable, which is the majority of patients with gastric and GEJ cancers. Often now with those patients, the data support neoadjuvant treatment in gastric cancer, usually neoadjuvant chemotherapy alone in newer regimens such as the FLOT regimen, which has shown improved survival outcomes compared to the older regimens like ECF.

In the case of GE junction adenocarcinoma, where there’s a role for radiation, most of the data would support neoadjuvant chemoradiation with the CROSS study regimen, which is fractionated radiation along with carboplatin and Taxol [paclitaxel] given weekly. Those are some of the main elements. I think if you have a situation where therapy is not given neoadjuvantly and then the patient is found to meet criteria for adjuvant therapy, there’s support to do that as well, obviously after surgery. But I think while looking at the trend over the last 10 or 15 years in these diseases, it has been to move more of the treatment to neoadjuvant as opposed to adjuvant.

The role of radiation and chemoradiation in neoadjuvant gastroesophageal junction is well demonstrated in regimens like the CROSS regimen, where the role of chemoradiation is important because some of the tumor may involve the gastroesophageal junction. However, in the stomach tumors like gastric cancer, the role of radiation is much more controversial. And recent studies, such as the CRITICS study, have suggested that there may not be much benefit to giving adjuvant radiation in some of those patients. We’re waiting for more studies that are ongoing now, such as TOPGEAR or ARTIST-2, that will further clarify the role of radiation in gastric cancer. But at this point in time, the only data we have for adjuvant in gastric cancer for radiation are relatively old data from the intergroup study, where there still was a role for chemoradiation in the adjuvant setting. It’s much more controversial as opposed to GEJ.

Transcript Edited for Clarity 
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