Caio Rocha Lima, MD, MS at Wake Forest Health - Appendix Cancer Survivorship Symposium

0:00 right now we have dr rosha lima presenting who he is an oncologist with wake forest baptist health and he'll be sharing today what's new in chemotherapy and immunotherapy for appendix cancer so the floor is yours thanks so much good afternoon everybody i will review and discuss systemic treatments for appendicito cancers these are my relevant financial relationships with

0:30 sponsors and grants this may have been presented already but it's not enough to emphasize that not all up in this year cancers are made the same we divide in two main subgroups one we call the eptelio neoplasms and those are the invasive adenocarcinomas the lower high grade appendiciometers neoplasms in the goblet cell adrenal carcinomas

1:00 and then there is a neuroendocrine group where differentiation is paramount in order to guide us how to select different treatment modalities and we break them down into well and poorly differentiated malignancies and then we further break it down into high intermediate and low grade that is a mix of neural neuroelectronic tumor and non-neuroendocrine plasma that's many times challenging and required a lot of interaction with pathology

1:32 in order to try to understand which tuba predominates so let's focus on systemic treatment and it's a multidisciplinary approach one size does not fit all we need to identify subgroups of patients particularly through research who benefit most from each therapy patients usually live long what is good it it reminds me of what i discuss with trainees is the difference between

2:03 incidence and prevalence we deal with many tumors in the colorectal in gi tract that have much higher incidence than appendicity or neoplasms but many of those have a shorter survival so when you stay long managing patients with appendicity or tumors not infrequent that you see that your clinic starts to have a predominance of appendicio tumors because of the longer survival over time your population becomes

2:35 more and more visible of patients of appendicity or tumors and this gives us opportunities to do second third fourth lines of treatment we have also to take into account the concept of methodologically active disease and that's an interaction with the pathologist and the treatment decision is based a lot on the aims of therapy not in not all time responses is what we really need many times we

3:06 want to focus on progression-free and you know most of most most of our overall survival and stable disease is as good as it gets in the disease like that particularly when you have a disease growth that tends to be slow so we have to really be worried about toxicities and when as a magic oncologist make the treatment selection i have to ponder that this treatment may be

3:38 part of the patient's plan for a long period of time so cumulative toxicity needs to be particularly taken into account so when we start the invasive subtype sorry in the a particular subtype invasive nanocarcinoma comes up not that infrequent and it's managed like patients with adenocarcinoma of the colon if you have a patient that undergoes an up in the cell reception

4:09 you know this this this may have already been presented but if the patient did not have an oncologic surgical procedure an oncological surgical procedure should take place with the resection of the appendix and a lymph node dissection and an appropriate number of lymph nodes available so we can appropriately stage the patient not infrequently after an appendectum you may still find residual tumor by doing a right side him colectomy or a for

4:41 oncologic surgery if you have a patient that has positive lymph nodes then i see them in my clinic the surgical team would would refer the patient to us because we would discuss adjuvant therapy with a fluoropytine like five fu or cape cyto being in a platinum like oxalia platinum for fox or kpox like we do any colon cancer and depending on the stage this could be up to three or six months for patients with stage two disease

5:09 we would discuss some of the pathological features that may be an indication that the patient may benefit from ashvan therapy that is also some genetic based data that we can use with some set of gene mutations that may be an indication that the patient should receive adjuvant treatment stage 2 disease and now more than ever we're using circulating tumor gna as a predictor of prognosis in the

5:39 stage two population as a guide to a consideration more aggressive and potentially adjuvant treatment for patients that presents a more advanced metastatic disease again we manage like colon cancer and the regimens are called fofox 5fu and oxalic platinum or fulfill with five of hearing chicken and biologic starts to play a role we have antigea hdf biological like bevacizumab ziva fibrocyte rhombic pseudomap that are all approved in colon cancer and can

6:11 and frequently use in appendicitonal carcinomas or anti-egfr therapy in patients that has rest extended this is a a capital gene colon cancer when it's not mutant we'll call wild type those patients benefit from anti-egfr treatment and asians are called panitumumab institute both approved in the united states now what another group of epithelial tumors that we still have lots to learn is called the mucinous appendiceo

6:43 neoplasms and those we divided according to the grade the low grade has been present and well established for a longer period of time and those patients generally do not respond from systemic chemotherapy and the value of systemic therapy in that population is debatable and then we have a relatively newer group called the high grade actually is not frequently observed and the pathology will tell us you know there is no invasion of what we call the lamina propria but the tumor is high

7:13 grade it tends to have a worse outcome than the low grade tumor despite of the lack of invasion of the alarm inappropriate and here again the jury is still out but there is some early evidence that systemic chemotherapy may have a role but still not as established as in the invasive animal carcinomas and then there is this subtype called the cinet ring histology and those patients tend to do and have a worse prognosis particularly in presence

7:40 of metastatic disease and here systemic chemotherapy has has a role there's another entity called goblet cell carcinoma called cell adenocarcinoma it was previously called and i think was a good change in the terminology it was previously called goblet cell carcinoids or adenocarcinoids because they are actually not frequently managed as neuroendocrine tumors they are mostly managed as adenocarcinoma so i think the terminology change is

8:11 adequate to guide us as medical oncologists and again this is not a disease that is frequently seen and you know the oncologist that is a general oncology would see one case or less a year of a goblet so adenocarcinoma and i think the chaining terminology would be a better way to direct treatment it is managing the adjuvant setting with treatment as we do in colon cancer in the metastatic setting again we need to meet with the

8:38 pathologists and understand how important the potential component of neonatal tumor is present but again we would tend to manage with a platinum and a fluid of an imaging like faux fox or k-box another presentation is when there is peritoneum dissemination and of what we called a rupture of the appendix and then the cells

9:10 occasional cells but basically mucin is present in the peritoneum could come up with work of a mucosil as well and that's called pseudomixing peritoneum as a medical oncologist have very little to offer in that regard this is basically a surgical entity and you know the treatment is to manage the patients according to symptoms and sometimes the bulking operations may have a row and over time it will cause problems so

9:40 you need to be monitoring followed by your oncology gene now shifting gears from the epithelium to the neuroendocrine group let's start with the well-differentiated neuroendocrine tumors and this comprises about 70 to 75 percent of neonatal neoplasms and are supervised according to the grade so you have well differentiated low intermediate and high grade tumors the low intermediate grade tends to have a better prognosis the timing of the cells

10:11 division is slower than the high grade they have an indolent behavior and in the low intermediate grade the role of chemotherapy is questionable we have most biologic approach to that i'm going to further discuss for the high grade subgroup that might be candidates for systemic chemotherapy what we call more orthodox system like chemotherapy and then there is another subgroup called the poorly differentiated neuroendocrine carcinoma that's about 20 to 25 of the endocrine tumors and here we

10:43 treat like small cell carcinomas those patients present with a very aggressive cancer where systemic hemotherapy basically made of a platinum and topozyed adreno chicken among other systemic treatments are of benefit and then you have the mixed type and it's very challenging this group and but many we will approach as a high-grade neonatal carcinoma because those tumors tends to be aggressive now you probably have heard and

11:15 there's a lot of information about carcinoid syndrome that may be a presentation in appendicity or tumors but interesting enough it is not as frequent present like in other sites of the gi tract the small bowel would be a presentation where patients would have neuroendocrine tumors that lead to carcinoid syndrome but occasionally we have an appendicion tumor that presents with an excess of production of vasoactive

11:46 substance particularly serotonin and the symptoms are very characteristics you have flushing wheezing and if not treated it may lead to a right-sided vowel or heart disease and the best way to manage that if it is not a surgical situation the tumor cannot be resected is to proceed with biologic agents that would block the receptors to serotonin and those biologic agents are

12:17 octreotide and eurotide now the patients with well-differentiated neuroendocrine tumors as i mentioned chemotherapy is not the paradigm here we would start with biologic agents like octreotide and rheotide by blocking the receptor it may actually have anti-growth effect in the tumors that have been true trials showing that octreotide may improve outcome all in rheotype may improve

12:48 outcome not only because of symptom control but also improvement in progression free in overall survival but when this does not control the tumor some of the patients may benefit from other biologics like avrolimus it's approved in that scenario and it's also effective in stabilizing the disease very uncommon to cause the tumor to shrink it's a pill you take it daily and it tends to be easier for the patient but there are significant side effects

13:19 including inflammation in the mouth cause stomatitis you can have difficulties in controlling your blood glucose you may develop inflammation in the lungs called pneumonitis so it has to be taken with a caveat and more recently that has been the development of a agent called luthertera it's lucio 177 that basically uses the octreotide as a transport to a nuclear

13:52 radioisotope called luciu177 that would then be delivered through the cancer cells through the octalotide binding and lead to cell death so that is being a very important recent achievement in that scenario and is currently approved in second or third line treatment patients that have a positive scan called a pet datatate so you need to have that skin being positive and by by that you understand that you

14:25 can develop the leucine 177 to the cancer cells in those patients that have the peptitate positive again another situation where the multidisciplinary team is important here you have the nuclear medicine physician helping us to identify those patients when we go to the high grade we are differentiating tumors now we live from the biologics and go into the more chemotherapeutic agents and here you have the temozolomide you also have the platinum metaposite in

14:57 the patient that have the positive pet dota tate that the lutisi 177 may be another approach and biologic like evrolymers and anti-vgf are also indicated in the puller differentiated he is straightforward systemic chemotherapy with platinum metoposite other agents that have been shown to be helpful in that situation including paclitak cell temozolomide that is another peel that can be very active in this situation arena chicken oxalic platinum toppo chicken here

15:29 immunotherapy appears to come up as being a potential benefit in that subgroup of patients early trials suggesting that it might be a row so in conclusions surgery is the only curative treatment for localized disease we need to interact in a multidisciplinary approach because we need the pathologist to tell us the proliferation index and morphology since those are cornerstones for tumor classification and impactable treatment and prognosis

16:00 systemic treatment varies according to a lot of the things that were discussed with you that includes somatostatin analogues target therapies chemotherapy in prg sequentially sequencing treatment is part amount because you have a situation where long survival is fortunately expected so you need to be careful about not causing toxicity that may limit limited quality of life thank you very much