update in the management of upper gi malignancy health/health...i will focus on the common...

Update in the Management of Upper GI Malignancy

Daniel D. Kirchoff, MDSurgical Oncology and General SurgeryRoper St. Francis Physician [email protected]

16th Annual Primary Care SymposiumDecember 3, 2016

mailto:[email protected]

Outline

• Esophageal Cancer• Gastric Cancer• Pancreatic Cancer• Liver Cancer• Head and Neck Cancer

Presenter

Presentation Notes

I will focus on the common pathologies in the upper GI tract

Goals

• Review presentation, workup, and treatment for the most common upper GI malignancies

• Review some of the controversies and changes regarding treatments

• Review the role of medications to prevent liver cancer and head and neck cancer

Presenter

Presentation Notes

Surgery has several roles in stage IV cancer. Palliation and diagnosis are important ones but I’d like to talk a little more about surgery as an effective therapy. Some of the traditional and rational arguments are that we are using a local tool for a systemic problems and that it is very morbid and the risks are way higher than the benefits.

Esophageal Cancer• Over 16,000 people in the US diagnosed in 2015

with over 15,000 deaths (1)• Distribution in the US has dramatically shifted

from squamous cell carcinoma (SCC) to adenocarcinoma (AC)

• SCC risk factors are strongly EtOH and tobacco, but not as much for AC

• Obesity and long-standing GERD are risk factors for AC

1. Siegel RL, et al. Cancer Statistics 2015. CA Cancer J Clin 2015;65(1):5-29.

Presenter

Presentation Notes

The reality is that more surgery IS being performed as we can see for a few representative cancers based on the nationwide inpatient sample.

Esophageal Cancer• Presents with dysphagia, post-prandial chest pain,

weight loss

• Workup includes endoscopy and endoscopic ultrasound

• Whole body imaging with both CT C/A/P and PET/CT (1)

1. Pfau PR, et al. The role and clinical value of EUS in a multimodality esophageal carcinoma staging program with CT and PET. Gastrointestinal Endosc 2007;65:3775-384.

Presenter

Presentation Notes

Presentation – especially in high risk people (Barrett’s, long-stnading GERD, obesity, smokers) Workup hinges on determining whether there is advanced disease and if neoadjuvant therapy is needed. Also important is where exactly the tumor is – since the proximal stomach is treated like the esophagus.

Esophageal CancerTreatment

• Early stage (in situ, T1a, some T1b) – endoscopic resection

1. Pfau PR, et al. The role and clinical value of EUS in a multimodality esophageal carcinoma staging program with CT and PET. Gastrointestinal Endosc 2007;65:3775-384.

Presenter

Presentation Notes

EUS is important here. Early lesions can be treated with EMR +/- ablation (this is also how Barrett’s with HGD can be treated Mention that this is something a lot of surgeons might say is not acceptable – but it is! For SCC – definitive non-surgicl treatment is also acceptable and even preferred given the morbidity of surgery.

Esophageal Cancer

1. Van Hagen P, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. NEJM 2012;366:2074-84.

T1b and greater requires multimodality therapy

CROSS Trial

• 75% AC of esophagus and GE junction

• Randomized to surgery alone or neoadjuvanttherapy

• 50 vs. 24 months median survival in the multimodality group

Presenter

Presentation Notes

Presentation – especially in high risk people (Barrett’s, long-stnading GERD, obesity, smokers) Workup hinges on determining whether there is advanced disease and if neoadjuvant therapy is needed. Also important is where exactly the tumor is – since the proximal stomach is treated like the esophagus.

Esophageal Cancer

1. Van Hagen P, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. NEJM 2012;366:2074-84.

T1b and greater requires multimodality therapy

Improved 5 – year overall survival with multimodality therapy regardless of histology

Presenter

Presentation Notes

This establishes the current standard of care using multiple chemotherapeutic agents carboplatin and paclitaxel with XRT for 5 weeks, then surgery within 6-8 weeks

Gastric Cancer• Over 26,000 people in the US will be diagnosed

in 2016 with over 10,000 deaths (1)• Vastly larger incidence in Asia and in Asians• H. Pylori infection, smoking, EtOH intake, high

salt intake are all risk factors• Cancers are more proximal in US

1. Siegel RL, et al. Cancer Statistics 2016. CA Cancer J Clin 2016;66:7-30.

Presenter

Presentation Notes

Proximal tumors are worse, for outcomes as well as for difficulty w surgical therapy and need for more extensive stomach removal. Distribution is different in Asian countries

Gastric Cancer• Presentation is variable from dysphagia to

bleeding from tumors.• Weight loss, anemia, abdominal pain

Presenter

Presentation Notes

Proximal tumors are worse, for outcomes as well as for difficulty w surgical therapy and need for more extensive stomach removal. Distribution is different in Asian countries

Gastric Cancer• Similar workup to esophageal• Endoscopy and EUS for initial staging• CT C/A/P, PET/CT• For early lesions, endoscopic therapy is

appropriate

Presenter

Presentation Notes

Workup includes basic labs, endoscopy for diagnosis, EUS for thickness and whole body imaging.

Gastric Cancer• For all but the earliest cancers, multimodality

therapy is critical

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The appropriate multimodality therapy for gastriic cancer is a very broad and confusing topic. What type of surgery? Chemo before or after? Radiation alone or with chemo, timing? Surgery alone as one arm of all the trials. This is a diagram representing active and recently completed clinical trials for the treatment of gastric cancer based on location and histology

Gastric Cancer• Type of surgery – limited (D1) vs. extended (D2)

Presenter

Presentation Notes

The first controversy in gastric cancer is how much surgery to do. In the US, there has not been a big emphasis on lymph nodes. A D1 dissection includes the nodesa round the stomach whereas and D2 resection included the nodes around the celiac axis, pancreas and spleen. In Japan and other Eastern countries, D@ often involved splenectomy and partial pancreatectomy as well with better survival compared to the US. Older gastric cancer trials demonstrated inproved survival for chemo and radiation but this was after “inadequate lymph node surgery”. Thought to maybe make up for inferior surgery.

Gastric Cancer

• Equivalent survival in D1 vs. D2 surgery in Italy but suggestion of improved survival if LN +

Presenter

Presentation Notes

The first controversy in gastric cancer is how much surgery to do. In the US, there has not been a big emphasis on lymph nodes. A D1 dissection includes the nodesa round the stomach whereas and D2 resection included the nodes around the celiac axis, pancreas and spleen. In Japan and other Eastern countries, D@ often involved splenectomy and partial pancreatectomy as well with better survival compared to the US. Older gastric cancer trials demonstrated inproved survival for chemo and radiation but this was after “inadequate lymph node surgery”. Thought to maybe make up for inferior surgery.

• MAGIC trial is widely but not univerallyconsidered the standard.

• Those undergoing curative resection should have chemotherapy or chemoradiation depending on extent of lymphadenectomy

Gastric Cancer

Presenter

Presentation Notes

MAGIC trial is standard although it is hampered by including GE junction tumos that we now consider esophageal, no standardized surgery with LN dissection all over the place

• So many variables make this a confusing landscape

• Recently, the harvest of 15LN was announced as a quality measure through the ACS Commission on Cancer.

Gastric Cancer

Presenter

Presentation Notes

Points to remember. D@ comes from Japan where it is quite possible the disease is different Dutch D1 D2 trial found no survival difference at 10 years, but at 15 years there was a slightl survival difference Ultimately the ACS CoC published a quality guideline recommending harvest of 15 LN, not specifying the extent. Multi organ resection for LN is widely considered to be excessive and un necessary. LOTS of trials with interesting names basically looking at pre and post-op treatment modalities including XRT before or after

• Looking at the SEER Medicare database, ethnicity and place of birth are searchable demonstrating that Asian patients born in Asia, Asians born in the US, and non-Asians have different tumors and survival

• Statistical analysis shows the difference is not related only to location or LN harvest

Gastric Cancer

1. Kirchoff DD, et al. Overall survival is influenced by birthplace and not extent of surgery in Asian Americans with resectable gastric cancer. J Gastrointest Surg 2015;19(11):1966-73.

Presenter

Presentation Notes

Interesting aspect of gastric cancer research is the difference between Eastern and Western patients. The pie charts represent the distribution of tumors within the stomach for different ethnic groups – foreign born Asians have the most lower or more favorable tumors. For all Asian patients, survival is improved if born outside the US. Multivariable analysis shows that the difference in survival is infludenced by stage, age and birthplace,but not LN harvest, tumor grade or tumor locations. H. Pylori strains, diet, and genetics are all possible factors.

• In 2016, over 53,000 people will be diagnosed and over 41,000 people will die with pancreatic cancer (1)

• Risk factors include pancreatitis, EtOH, tobbacco• Presentation commonly painless jaundice, vague abdominal

pain, weight loss

Pancreatic Cancer


Presenter

Presentation Notes

Most favorable presentation is often painless jaundice as the mass has grown enough to obstruct the sBD but prior to metastases

• Workup includes labs to evaluate jaundice• Tumor markers – CA 19-9• Imaging with pancreatic protocol CT (arterial, portal

venous, and delayed venous phases), or MRI/MRCP• Chest CT to complete staging, EUS/ERCP for diagnosis and

often relief of jaundice

Pancreatic Cancer


Presenter

Presentation Notes

Controversy of using EUS for diagnosis – some would argue if it is resectable it should come out and doesn’t need a biopsy.

• Imaging findings determine type of sugeryand timing of surgery

• Resectable• Borderline resectable• Unresectable

• Determined by vascular relationships

Pancreatic Cancer


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• Do we need a tissue diagnosis before treatment?

• Does everyone need chemotherapy?

Pancreatic Cancer


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• Do we need a tissue diagnosis before treatment?

• Does everyone need chemotherapy?

Pancreatic Cancer

Yes

Presenter

Presentation Notes

Everyone needs chemotherapy – the timing of chemotherapy is till in question

• Benefits of surgery upfront• Less post-operative morbidity• Option if difficulty making diagnosis• Can avoid a biliary stent

• Benefits of chemotherapy first• Avoiding surgery for biologically aggressive

disease• Higher rate of R0 resection• More likely to receive chemotherapy

Pancreatic Cancer


Presenter

Presentation Notes


• Resectable cancers

• Borderline resectable• These are tumors with very high rates of R1 resection• Phase II trial looked at neoadjuvant therapy for

resectable (23) and borderline resectable (39) patients led to over 80% rates of R0 resection for patients who made it to resection

Pancreatic Cancer

1. Kim EJ, et al. A multi-institutional phase 2 study of neoadjuvant gemcitabine and oxaliplatinwith radiation therapy in patients with pancreatic cancer. Cancer 2013;119:2692-2700.

Presenter

Presentation Notes

According to national guidelines, upfront surgical resection is acceptable for resectable lesions but we are participating in a randomized clinical trial to evaluate the outcomes of neoadjuvant therapy using the 2 accepted regimens for 3 cycles before surgrey and 3 cycles after surgery. Some patients will progress on therapy – they would not have been helped by an invasive surgery

• Technical aspects of surgery

Pancreatic Cancer

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Presentation Notes


• Often V.O.M.I.T.

• Workup

Pancreatic Cystic Lesions


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Presentation Notes

VOMIT – incidentaloma Workup hinges on further imaging, history, and often EUS

Pancreatic Cystic Lesions


Presenter

Presentation Notes

VOMIT – incidentaloma Workup hinges on further imaging, history, and often EUS

Liver and Bile Duct Cancers• Bile duct cancers (gallbladder CA and cholangiocarcinoma)

were diagnosed in over 10,600 patients in the US in 2015 with close to 4,000 deaths (1)

• Risk factors include chronic inflammation, primary sclerosing cholangitis and inflammatory bowel disease

• Presentation commonly painless jaundice, vague abdominal pain, weight loss


Presenter

Presentation Notes


Cholangiocarcinoma• Diagnosis includes labs and

LFTs, and imaging, often with ultrasound demonstrating biliary ductal dilatation

• Tumor marker – CEA, CA 19-9• Imaging – CT w contrast,

MRI/MRCP• Staging – PET/CT especially

important due to the high likelihood of occult metastatic disease


Presenter

Presentation Notes


Cholangiocarcinoma• Treatment depends of location• Intrahepatic• Extrahepatic

• Hilar (Kaltskin’s tumor)• Distal bile duct

• Gallbladder


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Cholangiocarcinoma• Treatment

• Surgery• GB – radical

cholecystectomy• GB, lymph nodes,

segment 4B and 5


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• Surgery• Cholangiocarcinoma• Extrahepatic• Extrahepatic bile

ducts and lymph nodes


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• Surgery• Cholangiocarcinoma• Extrahepatic• Extrahepatic bile

ducts and lymph nodes

• Biliary reconstruction


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• Surgery• Intrahepatic –

segmental resection• Involved segment

sparing parenchyma as much as possible

• No lymph nodes

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Presentation Notes



• Surgery• Hilar – Extended

resection• Resection depends on

involvement of blood vessels, ERCP results and amount of liver left behind

Presenter

Presentation Notes

Need to touch on lack of need for biopsy Surgical exploration often fails due to unknowables

Hepatocellular Carcinoma

1. Horgan AM, et al. Adjuvant in the treatment of biliary tract cancer: a systemic review and meta-analysis. J Clin Oncol 2012;30:1934-1940.

• Liver cancer (HCC) was diagnosed in an estimated 35,000 patients in 2015 with over 24,000 deaths(1)

• Risk factors are very well-defined and include hepatitis and cirrhosis – including non-alcoholic steatohepatitis (NASH), along with EtOH abuse, aflatoxin exposure

• Presentation often non-specific including pain, jaundice, malaise, and weight loss

• Screening patients at high risk plays an important role

Presenter

Presentation Notes


Screening

1. Zhang BH, et al. Randomized controlled trial of screening for HCC. J Cancer Res Clin Oncol2004;130:417-422.

• Based on large RCT from China demonstrating Q6 month U/S and alpha fetoprotein (AFP) level in Hep B or chronic hepatitis patients led to 37% decrease in mortality from HCC

• In the US, the AASLD doesn’t recommend use of AFP but it is still commonly used

• High risk population: viral or non-viral cirrhosis (including NASH), and Hep B carriers without cirrhosis

• US screening q 6 months (commonly w AFP)• A liver nodule will prompt contrasted CT or MRI• Lesions <1cm can be followed q 3 months

Presenter

Presentation Notes

RCT from China with results inspite of less than 60% of patients completing screening

HCCTreatment and workup

• Diagnosis can be made with classic enhancement pattern on imaging or needle biopsy

• Chest imaging and bone scan (only for symptoms) for staging

• Assessment of liver remnant volume and portal hypertension

• Multidisciplinary care• Surgery, Embolization, Ablation, radiotherapy, transplant

Presenter

Presentation Notes

Treatment options vary widely and are multifactorial. Transplant indicated under certain guidelines, surgery has a lower recurrence rate thatn TACE/Ablate but only marginally so it is a truly multidisciiplinary team decision – which we review the last Tuesday of each month.

Multidisciplinary treatment options• A lot of our experience comes from colorectal liver mets

and retrospective data

• No change in OS, but delayed progressionin the liver

1. Siegel RL, et al. SIRFLOX. CA Cancer J Clin 2016;66:7-30.

Presenter

Presentation Notes

Selective internal radiation theapy (SIRT) or radioemboliztion delivers radiation in the form of small spheres embedded with Yttrium 90 radio-eluting beads.

Multidisciplinary treatment options• Y-90 radioembolization utilized the tumor’s arterial blood

supply as opposed to healthy liver’s portal system blood supply


Presenter

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This is for more than just HCC TACe, ablation, Y-90

Multidisciplinary treatment options• Y-90 radioembolization utilized the tumor’s arterial blood

supply as opposed to healthy liver’s portal system blood supply


Presenter

Presentation Notes

This is a scale represenatation of the size of the spheres that can get into the arteriolar blood supply but not into the circultion and essectially occlude the terminal blood supple of the tumor and radiate for about 2 weeks.

Multidisciplinary treatment options• JH is a 87yo man presented in 9/2015 with metastatic

sigmoid colon CA

9/29/2015

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Multidisciplinary treatment options• JH is a 87yo man presented in 9/2015 with metastatic

sigmoid colon CA

10/29/2015

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Multidisciplinary treatment options• He underwent “gentle” chemotherapy and Y-90

embolization x 2

2/5/2016

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Much less PET activity

Multidisciplinary treatment options• Sigmoid colectomy to deal with primary 3/2016, followed

by “real” chemotherapy and re-imaging

9/20/201610/31/2016

Presenter

Presentation Notes

Much less PET activity Next step will be another round of Y-90 to deal with the remaining metabolically active portion of the tumor.

• Can vaccines really prevent or treat cancer?

Vaccines and Cancer

Presenter

Presentation Notes

Of course there have been significant advances in cancer care and imporvements in mortality including immunotherapy most recently. But the most effective and successful strategy remains preventing cancer and detecting it early. 2 disease have recent and poignant examples of how we can intervene to really halt the spread.

• Can vaccines really prevent or treat cancer?• Hepatitis C is the leading cause of HCC• Previous treatment was tedious and led to 40-45% cure rates• Harvoni is a combination ledipasvir/sofosbuvir pill

Vaccines and Cancer

1. Afdhal N, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. NEJM 2014;370(16):1889-98.

Presenter

Presentation Notes

Havoni is much better tolerated and leads to grater than 90% virologic cure rates

• Can vaccines really prevent or treat cancer?• Hepatitis C is the leading cause of HCC• Previous treatment was tedious and led to 40-45% cure rates• Harvoni is a combination ledipasvir/sofosbuvir pill

Vaccines and Cancer

1. Afdhal N, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. NEJM 2014;370(16):1889-98.

Presenter

Presentation Notes

Of course there have been significant advances in cancer care and imporvements in mortality including immunotherapy most recently. But the most effective and successful strategy remains preventing cancer and detecting it early. 2 disease have recent and poignant examples of how we can intervene to really halt the spread.

• Can vaccines really prevent or treat cancer?• HPV is a very common virus, certain strains of which have

long been known to lead to cervical cancer • HPV 6,11,16, 18 are the virulent forms and now have been

increasingly implicated in head and neck squamous cell cancer.

• According to the CDC: • 11-12 year olds should get 2 doses of HPV vaccine 6-12

months apart (as of 10/19/2016).• Women up to 26 should be vaccinated• Men to age 21 and high risk populations to age 26

Vaccines and Cancer

1. Agalliu I, et al. Associateions of alpha, beta, and gamma-HPV types with risk of incident head and neck cancer. JAMA Oncol 2016;2(5):599-606.

2. Saraiya M, et al. US assessment of HPV Types in cancers: Implications for current and 9-valent HPV vaccines. J Natl Cancer Inst 2015; April 29;107(6).

Presenter

Presentation Notes

Havoni is much better tolerated and leads to grater than 90% virologic cure rates

• This vaccine has proven to decrease rates of cervical, genital, anal, and oropharyhngeal infection with HPV.

• Will this lead to decreased incidence of cancer?

Vaccines and Cancer


Presenter

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These are the cancer incidences associate with HPV

• This vaccine has proven to decrease rates of cervical, genital, anal, and oropharyhngeal infection with HPV.

• Will this lead to decreased incidence of cancer?

Vaccines and Cancer


Presenter

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These are the cancer incidences associate with HPV and in very high percentages for many so while there will always be outliers, a lot of these cancers should be drastically reduced in the next 10-20 years or sooner.

Conclusion

• Review of incidence, workup, and treatment of upper GI malignancies

• Multidisciplinary treatment strategies are expanding the pool of candidates for successful treatments

• Surveillence can help diagnose more early cancers for some diseases (HCC mainly)

• Vaccination will make a major difference in the next decade for HPV and HCV related cancers

Presenter

Presentation Notes

Not all patients are surgical candidates and not all tumors can be removed surgically so microwave ablation is a long-studied method of tumor destruction that is good on its own and even better combined with surgery

Thank You

update in the management of upper gi malignancy health/health...i will focus on the common...

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