Multidisciplinary treatment and immunotherapy improved the prognosis of advanced small intestine sarcomatoid carcinoma

, Small intestine sarcomatoid carcinoma ( SISCA ) is a r ar e type of malignancy, with an annual incidence rate of 0.5–0.8 cases per 100 000 people [ 1 ,2 ]. It is c har acterized by the pr esence of both cancerous and sarcomatous components [ 3 ]. Curr entl y, there is no standardized treatment for SISCA. In cases of advanced disease, patients typically undergo chemotherapy regimens similar to those used for colorectal tumors, such as fluor our acil, oxaliplatin, and irinotecan. Ther e hav e been no reported cases of targeted therapy or immunotherapy for SISC A. Here , we present a case of a male patient with tumor mutational burden-high ( TMB-H ) SISCA with liver and lung metastases that sho w ed a fav or able r esponse to m ultidisci-plinary treatment. It may provide valuable information for future treatment.

Dear Editor, Small intestine sarcomatoid carcinoma ( SISCA ) is a r ar e type of malignancy, with an annual incidence rate of 0.5-0.8cases per 100 000 people [ 1 ,2 ].It is c har acterized by the pr esence of both cancerous and sarcomatous components [ 3 ].Curr entl y, there is no standardized treatment for SISCA.In cases of advanced disease, patients typically undergo chemotherapy regimens similar to those used for colorectal tumors, such as fluor our acil, oxaliplatin, and irinotecan.Ther e hav e been no reported cases of targeted therapy or immunotherapy for SISC A.Here , we present a case of a male patient with tumor mutational burden-high ( TMB-H ) SISCA with liver and lung metastases that sho w ed a fav or able r esponse to m ultidisciplinary treatment.It may provide valuable information for future treatment.
In July 2021, a 61-year-old male presented with a 1-month history of abdominal pain.Computed tomogr a phy ( CT ) scans r e v ealed a mass at the junction of the duodenum and jejunum, and a thick-walled cavity with solid nodules in the posterior segment of the right lo w er lung lobe ( Fig. 1 A ) .Gastrointestinal endoscopy identified an ulcer ativ e neoplasm in the horizontal section of the duodenum, with preliminary pathology suggesting malignancy.Due to the potential for further growth leading to intestinal obstruction, r adical sur gical r esection of the small intestine tumor was performed in August 2021.Postoper ativ e pathology indicated sarcomatoid carcinoma ( SCA ) infiltrating the entire intestinal w all, inv olving nerve tissue, with tumor thrombus in blood vessels.Examination of one superior mesenteric vein, one artery node and five peri-intestinal lymph nodes revealed no tumor metastasis ( pT3N0Mx ) .Immunohistochemistry sho w ed pr ogr ammed cell death ligand 1 ( PD-L1 ) had a tumor pr oportion scor e of 35% and a combined positiv e scor e of 45.Next-generation sequencing of the small intestine specimen r e v ealed TMB-H ( 13Mut/Mb ) .Then a lung lesion biopsy confirmed SCA.Follo wing multi-disciplinary discussion, w e considered that postoper ativ e c hemother a p y w as necessary and that the patient would benefit more from combination immunotherapy because of the high PD-L1 expression and TMB-H of tumor cells.So the patient adopted Nab-paclitaxel ( 100 mg/m 2 day 1, e v ery 2 weeks ) , oxaliplatin ( 85 mg/m 2 day 1, e v ery 2 w eeks ) , leucov orin ( 400 mg/m 2 day 1, e v ery 2 weeks ) , and fluor our acil ( 1200 mg/m 2 day 1-day 2, e v ery 2 weeks ) combined with pembr olizumab ( 200 mg day 1, e v ery 3 weeks ) for thr ee cycles.A r eassessment r e v ealed disease pr ogr ession with ne w liv er metastases ( Fig. 1 A ) .The treatment plan was changed to irinotecan ( 190 mg/m 2 day 1, e v ery 3 weeks ) and capecitabine ( 800 mg/m 2 twice a da y, da y 1-day 14, e v ery 3 weeks ) combined with be v acizumab ( 7.5 mg/kg, day 1, e v ery 3 weeks ) .Unfortunatel y, the patient experienced se v er e febrile neutr openia ( FN ) , leading to the discontinuation of anti-tumor treatment.After recovery from FN, the patient underwent another two cycles of reduced-dose treatment.Five months after r eceiving postoper ativ e ther a p y, a follo w up r e v ealed no significant changes in lung and liver lesions.After multidisciplinary discussion again, we believed that systemic treatment plus local tr eatment of liv er and lung lesions may ac hie v e better r esults than systemic treatment alone.So radiofrequency ablation ( RFA ) was performed on the liver lesion, and surgical removal was conducted for the lung lesion, with no residual tumor observed in the postoper ativ e pathology examination of the lung ( Fig. 1 B ) .The patient has since entered the follow-up stage, and the latest r outine c hec kup in May 2024 indicated no evidence of disease ( NED ) .
SCA is documented in the liter atur e to occur in various locations such as the r espir atory tr act, gallbladder, esophagus, stomach, kidne y, and blad der.Primary SCA originating in the small intestine is extr emel y r ar e, with fe wer than 55 r eported cases to date.Clinical manifestations typically include symptoms of intestinal obstruction or intussusception.SISCA primarily affects middle-aged and elderly men [ 4 ].The diagnosis of SISCA is primarily based on histological appearance and immunohistoc hemical e vidence .T his type of tumor is less sensitive to r adiother a py and c hemother a py.In a study summarizing 20 patients by Reid-Nicholson et al .[ 4 ], 14 patients died within 2 months to 3 years after dia gnosis.Additionall y, the tumor exhibits low differ entiation, str ong inv asiv eness, high pr opensity for metastasis , and poor prognosis , with a 5-year survival rate close to 0% [ 5 ].The initial treatment modality for early-stage patients is sur gical interv ention; for adv anced-sta ge patients, c hemother a py is emplo y ed as the primary tr eatment a ppr oac h, with r efer ence to colorectal cancer protocols.In recent years, with the rise of imm unother a py, pr omising r esults hav e been ac hie v ed in the tr eatment of micr osatellite instability high or TMB-H colorectal cancer.Studies such as KEYNOTE-158, TAPUR, and MyPathway suggest that TMB-H and high PD-L1 expression are potential ther a peutic tar gets in gastr ointestinal tumors, impr oving patient pr ogr ession-fr ee surviv al and ov er all surviv al [6][7][8].Ho w e v er, ther e hav e been no reports on the use of imm unother a py in SISCA.We adopted a sta ged a ppr oac h involving c hemother a py combined with imm unother a py, c hemother a py combined with targeted ther a py, and local tr eatments .To date , the patient has shown no r ecurr ence or metastasis, and disease-free survival has r eac hed 24 months.Pr e vious liter atur e suggests that patients with small intestinal SCA typically succumb within 3 years; this patient has been diagnosed for nearly 3 years without r ecurr ence or metastasis, indicating se v er al factors contributing to a favor able prognosis .( i ) T he patient's TMB-H and high PD-L1 expression result in greater benefits from immunotherapy.Although new liver lesions a ppear ed after thr ee cycles of imm unother a py, they ar e likel y pseudo-pr ogr ession [ 9 ]. ( ii ) The stable and localized liver and lung lesions prompted the multidisciplinary team to opt for aggr essiv e local treatment.
It is important to note that the patient experienced drugr elated adv erse r eactions during tr eatment, whic h underscor es the need for close monitoring of toxic side-effects during treatment and individualized treatment adjustments.Ho w ever, due to the rarity and high heterogeneity of the disease, more cases and clinical r esearc h ar e needed to further clarify the optimal treatment options and prognostic factors.
In conclusion, the multi-disciplinary treatment provided clinical benefits for the reported case of SISCA.Molecular profiling pr ovided a pr ecise, individualized guide.We belie v e that SISCA patients with markers of benefiting from immunotherapy should be activ el y tr eated with imm unother a py and the a ppr opriate time for local treatment sought to improve their prognosis.

Ac kno wledgments
This study was supported by the National Health Commission Medical and Health Technology Development Research Center, Innov ativ e Drugs Clinical Research Fund ( Grant No. WKZX2023CX090001 ) and the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sic huan Univ ersity ( Gr ant No. ZYJC21017 ) .We would like to thank the patient for his assistance in providing information and written informed consent.We would also like to thank the pathologists for their support in offering histopathological images.

Figur e 1 .
Figur e 1. Treatment details , ima ging r adiogr a phic findings and lung metastases histological a ppear ance.( A ) Ima ges of c hest and abdomen CT at different time points.( B ) Histological appearance of lung metastases before and after treatment ( ×400 magnification ) .PD, Progressive disease; SD, stable disease.