primary peritoneal serous carcinoma ( ppsc ) has a clinical profile similar to ovarian cancer 1 . adjuvant paclitaxel  carboplatin therapy ( tc ) showed almost identical , favorable results regarding survival rates in patients with ppsc and ovarian cancer 2 ; however , once recurrence happens , ppsc becomes difficult to manage with tc alone . active , specific immunotherapy using the patient 's tumor cells can elicit a long - term cell - mediated immune response and succeeds in treating melanoma and colon cancer 3,4 . formalin - fixed cells and paraffin - embedded tumor tissues are also good sources of alternative tumor - associated antigens for autologous cytotoxic t - cell induction 5,6 . autologous formalin - fixed tumor vaccine ( aftv ) was developed on the basis of this principle 7,8 . a prospective randomized clinical trial showed that aftv significantly decreased the incidence of early recurrence in patients with hepatocellular carcinoma who had undergone hepatic resection alone 9 . other pilot and phase i / iia studies for glioblastoma multiforme indicated that such therapy was effective without notable complications 10,11 . therefore , aftv has been considered to be applicable to many types of solid tumors , such as high - grade malignant fibrous histiocytoma in combination with radiotherapy 12 . in this background , we tried to treat a case of tertiary - recurrent ppsc with tc and aftv , which seemed difficult to manage with tc alone . a 57-year - old woman presented an abnormal endometrial pap smear , which was suspicious for adenocarcinoma and was systemically explored . she underwent laparoscopic laparotomy , which identified adenocarcinoma on the surfaces of her ovary , omentum , and peritoneum . after undergoing a total abdominal hysterectomy , bilateral salpingo - oophorectomy , total omentectomy , pelvic lymphadenectomy , and exploratory excision of the right crus of diaphragm she had an elevated ca125 level ( 1335  u / ml ) after 26  months of time to progression ( ttp ) by the first postoperative paclitaxel ( 180  mg / m ) plus carboplatin ( cbdca ; area under the curve 6 ) therapy ( tc ) comprising six courses . positron emission tomography - computed tomography ( pet - ct ) showed recurrence at the small bowel , which was observed only on the surface of the ileum . as a result a second tc comprising six courses was administered ; however , after 20  months of ttp , the ca125 level was elevated again ( 84  u / ml ) . she underwent tc a third time , which comprised five courses . after resulting 8.3  months of ttp , the ca125 level continuously increased from 17.9  u / ml ( day 0 ) to 2586  u / ml ( day 91 ) ( see fig.1 ) . pet - ct revealed multiple hot spots around the right crus of the diaphragm , liver , and mesentery ( day 85 ) ( see fig.2 , left ) . tc was again attempted ; however , after initiation of the  fourth tc ( day 97 ) , the ca125 level increased to 3571  u / ml ( day 105 ) . at that point , a decision was made to combine tc and aftv . the ca125 level continuously increased from 17.9  u / ml ( day 0 ) to 2586  u / ml ( day 91 ) . tc ( solid arrows ) began on day 97 , and intradermal injections of aftv ( open arrows ) commenced on day 116 . following initiation of this therapy , ca125 levels dramatically decreased from 3571  u / ml ( day 105 ) to 244  u / ml ( day 133 ) . levels continued to decrease from 53.6  u / ml ( day 161 ) to 29.3  u / ml ( day 189 ) to 15.8  u / ml ( day 281 ) . pet - ct images before and after tc and aftv . left : multiple hot spots around the right crus of the diaphragm , liver , and mesentery are visible . aftv , autologous formalin - fixed tumor vaccine ; tc , paclitaxel  carboplatin therapy ; pet - ct , positron emission tomography - computed tomography . first the formalin - fixed , histologically confirmed neoplastic tissue was thoroughly fragmented and centrifuged . then , an alcohol extract preparation of freeze - dried bacillus calmette  gurin vaccine ( japan bcg laboratory , tokyo . tokyo , japan ) was added , washed , and suspended in 1  ml of saline with 250  ng of tuberculin microparticles and 250  ng of soluble tuberculin ( japan bcg laboratory , tokyo ) . after obtaining informed consent from the patient , she received three intradermal injections of aftv at 2-week intervals . the day after the third aftv injection , skin erythema and induration were observed , suggesting delayed - type hypersensitivity reaction around inoculated points ; this finding persisted for only 7  days . the blood ca125 levels dramatically decreased to 244  u / ml ( day 133 ) , 53.6  u / ml ( day 161 ) , 20.4  u / ml ( day 224 ) , 17.9  u / ml ( day 251 ) , and 15.8  u / ml ( day 281 ) ( fig.1 ) . pet - ct revealed no visible mass ( day 189 ) ( fig.2 , right ) . however , ca125 levels dramatically increased again from 24.8  u / ml ( day 310 ) to 830  u / ml ( day 344 ) . because the entire specimen was used to prepare the three aftv , additional chemotherapy without aftv was performed with tc ( only one course ; no response ) , followed by gemcitabine monotherapy ( no response ) , and finally , topotecan ( no response ) for example , tc affects patient survival rates in a similar and favorable manner 2 . a traditional phase ii study evaluating the efficacy of tc for platinum - sensitive recurrent ovarian cancers demonstrated an observable response in 75.6% ( 26.8% complete response , 48.8% partial response ) of cases 13 , but incidence of the response to tc decreased in the context of ppsc recurrence . in this case study , the patient 's ttp was 26 , 20 , and 8.3 months after the first , second , and third tc , respectively . when ppsc recurred after the third tc , the ca125 level continued to elevate to 3571  u / ml even after initiating a fourth tc ; this response pattern differed from those of the former tc applications in which the ca125 level decreased in response to therapy . when tc was combined with aftv , the patient responded dramatically to the additional aftv and did not develop severe adverse effects . in addition , the patient showed a ttp of 11.5  months , which was longer than that of the third ttp . because formalin fixation preserves the specific antigenicity of tumor cells 5 and preparation of aftv from resected and fixed tumor tissues 10,11 is simple , furthermore , after the patient received tc and aftv , no visible lesions were detected by pet - ct . these findings suggest that tc and aftv could serve as a new strategy for recurrent ppsc , which is unmanageable with tc alone . the feasibility and efficacy of complete laparoscopic staging was demonstrated in early stage ovarian cancer 14 ; however , in advanced stage , the role of laparoscopy has been limited in cytoreductive procedures . in this case , cancer mass was observed on the surfaces of the ovary , omentum , peritoneum , and right crus of diaphragm , and laparotomy was rationally indicated for optimal maximum cytoreduction . the efficacy of intraperitoneal ( ip ) chemotherapy preceded by cytoreductive surgery was reported in advanced ovarian cancer 15 . in this case , consecutive cytoreductive laparotomy after laparoscopic survey was seemed to be appropriate , and we do not adopt ip chemotherapy due to the possibility in severe adverse events , such as grade 34 pain , ileus , diarrhea , or an associated complication of ip catheter , which might worsen quality of life in spite of the expected promising survival by ip 16 . latest immunotherapeutic advancements in the treatment of tumors 1719 should be taken in consideration for this type of patients . in this case study , the patient gained approximately a year of progression - free survival time after the recurrence of tc - resistant ppsc , which implies that this type of immunotherapy may be a viable treatment option for chemo - refractory recurrent ppsc . written informed consent was obtained from the patient for publication of this case report and accompanying images . the authors declare that they have no conflict of interest , except that to works at a private company known as cell - medicine , inc .
key clinical messagepaclitaxel  carboplatin therapy ( tc ) usually controls primary peritoneal serous carcinoma ( ppsc ) but not recurrent disease . in this case 
 , ppsc recurred after three courses of tc , responded dramatically to additional autologous formalin - fixed tumor vaccine ( aftv ) , and resulted in prolonged , progression - free survival without visible lesions detected by positron emission tomography  computed tomography .