Apurna Jegannathen, MD @sngilani @UHNM_NHS #pancreaticcancer #cancer #research A Sustained Response of Maintenance Therapy in PACC

Apurna Jegannathen, MD @sngilani @UHNM_NHS #pancreaticcancer #cancer #research A Sustained Response of Maintenance Therapy in PACC

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Apurna Jegannathen, MD from University Hospital Of North Midlands discusses the abstract A Sustained Response of Maintenance Therapy in Pancreatic Acinar Cell Carcinoma (PACC): A Case Report and Literature Review.


The Study:
Maintenance Therapy; Pancreatic Acinar Cell Carcinoma (PACC); Gemcitabine; Oxaliplatin; CapecitabineWe recognize 50-year-old male patients who have been histologically diagnosed with acinar cell tumor of the pancreas. He originally had localized pancreatic cancer. He underwent distal pancreatectomy with splenectomy for pT3pNxpMxR1 condition, con-anaphylaxis. Upon disease recurrence, oxaliplatin + capecitabine was initiated but stopped after 5 cycles due to disease progression. Oddly, however, later CT scans after 3 months showed a disease response that persisted for almost 6 months without any medication. We believe it was an odd late answer. But unfortunately, shortly after this, his condition got worse again. We re-challenged him with the same chemotherapy at that time. More than four years after his initial diagnosis, this patient on maintenance therapy showed more clinical and radiological improvement in his illness.

Introduce
Every year, 8463 new cases of pancreatic cancer in the UK are diagnosed. The prevalence of pancreatic cancer in the UK has remained the same over the past two decades, affecting equal proportions of males and females, accounting for 3 percent of all new cancers. The incidence of pancreatic cancer would increase because of the population's longevity. Pancreatic tumours may be caused by either the endocrine or exocrine part of the pancreas. Almost 95% of these cancers derive from the ductal component and are exocrine in nature. Pan-creatic acinar cell carcinoma (PACC) is a rare tumor consisting of 1 to 2 percent of exocrine pancreatic cancers. PACC is genomically distinct from other pancreas cancers.

Context
An acinar cell carcinoma is a rare form of malignancy of the pancreas that accounts for only 1-2% of all pancreatic cancers. They seem to have more men at the age of seventy. Presentation signs are usually non-specific. It is also related to elevated serum levels of lipase. We are focusing on a young man who suffered from general ill-health and weight loss at the age of fifty. His disease not only reacted well to the initial chemotherapy,
But they also remained healthy on maintenance chemotherapy. He lived for 48 months after his initial diagnosis.

Study Report
There was weight loss and general fatigue reported by a 50-year-old man. He had no clear previous medical record or family history. His WHO production status was zero. Picked-up CT scans for a left hypochondrial mass that was later confirmed histologically as adenocarcinoma. He underwent a splenectomy and a distal pancreatectomy. As well as differentiated acinar, cellular pancreatic carcinoma (pT3 pNx pMx R1) returned to final histology. Gemcitabine adjuvant chemotherapy was introduced but abandoned because of the anaphylactic reaction. Three months later, a CT surveillance scan raised local recurrence issues and possible liver metastases. These findings were confirmed by the PET CT scan. The Oxaliplatin plus Capecitabine protocol was therefore initiated in palliative settings. After 5 cycles, his condition tended to worsen.
In the liver of you. He declined to participate in a clinical trial or to undergo further chemotherapy treatment. He suffered pain in his abdomen three months later. Surprisingly, CT scanning at the time.
Pancreatic tumor shrinkage was observed and liver lesions vanished. This phenomenon may be a result of a late reaction to previous chemotherapy. But unfortunately, six months later, his condition, which was supported by CT and MRI scans, deteriorated again. A decision to re-challenge Oxaliplatin plus Capecitabine was made. After 4 more cycles, a remarkable response was seen again. We had to stop oxaliplatin due to neurotoxicity, but we continued maintenance with a single agent called capecitabine. Further imaging, also 48 months after its initial progression, revealed a persistent response without any further growth.
About diagnosis. This patient remained on maintenance therapy with reasonable performance status for four years from their initial diagnosis.
The ongoing response of the disease to maintenance treatment with capecitabine has been observed. He was monitored with regular surveillance CT scans until his illness progressed.

Discussion 
Acinar carcinoma is more prevalent in men than in women between the average age of 60 and 70. Typically, weight loss, nausea, and stomach pain are present.
The level of serum lipase may be increased in some patients manifesting Schmid's triad consisting of polyarthritis, eosinophilia, and fat necrosis. Endocrine defects in rare acinary cell carcinomas may also occur. In this sense, our case is rare since the patient is relatively young and has symptoms, i.e. weight loss and constitutional symptoms, that are known to occur in this type of cancer.
For most pancreatic cancers, the prognosis is poor. The mean survival remains 4 to 8 months for advanced pancreatic cancers.
There are no clear guidelines for the treatment of tumors of the acinar cell. At present, this rare form of malignancy is being treated in almost the same way as other types of exocrine pancreatic tumors. Gemcitabine has been the mainstay of treatment for advanced pancreatic cancer (APC) for many years. Unfortunately, when gemcitabine was added to different chemotherapeutic agents, some earlier trials did not show survival benefits. However, two meta-analyses later found that the combination of gemcitabine with either capecitabine or oxaliplatin resulted in overall survival becoming substantially longer. Recently, a triplet combination regimen has been tested (Gemcitabine, Oxaliplatin, and Capecitabine).
The median period is increased to 4.3 months of progression by certain APC benefits. But this comes with the price of toxicity and rapid growth in resistance.
A similar case of pancreatic acinary cell carcinoma was documented by Monique Antoine, et al., who survived for 37 months after treatment with multiple chemotherapeutic agents, in 2007. In this regard, however, our case is exceptional in that it survived for much longer after just one single regimen of oxaliplatin + capecitabine followed by maintenance chemotherapy with capecitabine alone.

Conclusion
Late response and long-term disease stabilization may occur in some patients and maintenance chemotherapy may be possible. This may be due to underlying biological and genetic factors that must be further explored by genomic profiling. In more than two-thirds of these tumors, for instance, RAF gene fusions and mutually exclusive inactivation of DNA repair genes are novel potential therapeutic targets altered.

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