Costs and clinical outcome of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from gastric cancer

Figures & data

Table I. Demographic- and basic clinical data for patients in CRS + HIPEC + EPIC group.

Pat.	Age (years)	Gender (M, male; F, female)	Clinical characteristics
1	58	F	Diagn. lap.:tumour-growth in gastric serosa + little PC, Dec 2004.
2	72	M	Gastroscopy: linitis plastica. Diagn. lap.:PC at left diaphragm + left paracolic gutter, Jun 2005.
3	48	F	Gastroscopy: advanced distal tumour. Diagn. lap.:PC (diaphragm + lig.teres hepatis), Jul 2005.
4	70	F	Gastroscopy: rigid wall distally, no cancer in autopsy. Diagn. lap.: distal gastric tumour + spread PC, Nov 2005.
5	57	M	Gastroscopy: large central tumour-ulcer, cancer in autopsy. Diagn. lap.: gastric tumour with serosal growth + spread PC (small intestine meso, gallbladder, liver, pelvis), Dec 2005.
6	67	F	Gastroscopy: cardiac tumour, cancer in autopsy, Nov 2004. Expl. laparotomy: gastric tumour with serosal growth + spread PC (small intestine meso, lesser omentum, falciform lig.,hepatoduodenal lig., gallbladder) + asciites, Feb 2005.
7	60	M	Diagn. lap.:tumour-growth in gastric serosa + little PC (greater omentum + gallbladder), Apr 2005. Intention to CRS + HIPEC, but expl. laparatomy: extensive tumour growth on the entire small intestine serosa.
8	57	F	Diagn. lap.:tumour-growth in gastric serosa + PC (left and right diafragm), Dec 2006. Intention to CRS + HIPEC, but expl. laparatomy: extensive tumour growth on the entire small intestine serosa.
9	38	M	Gastroscopy: cardiac tumour, cancer in autopsy, Dec 2006. CT: large prox. tumor on minor-side, enlarged lymph nodes at minor-side and spleen; Diagn. lap: little PC (falciform lig.), Jan 2007.
10	57	M	Gastroscopy: bleeding corpus tumour, cancer in autopsy,. Diagn. lap:PC (left and right diaphragm, falciform lig.) + asciites, Dec 2006. Progress during neo-adjuvant chemo.

CRS, cytoreductive surgery; HIPEC, hyperthermic intraperitoneal chemotherapy; EPIC, early postoperative intraperitoneal chemotherapy;PC, peritoneal carcinomatosis.

Table II. Demographic- and basic clinical data for patients in systemic chemotherapy treatment group.

Pat.	Age (years)	Gender (M, male, F, female)	Clinical characteristics
11	59	F	Gastectomy + splenectomy (scirr. cancer), no PC, 2004. CT Oct 2004: PC in greater omentum + enlarged lymph node at the place for splenectomy.
12	61	F	Gastectomy + splenectomy (pT2N0M0), no PC, 2003. CT Jan 2005: residual tumour in the anastomose with growth to environment + enlarged paraaortic lymph nodes.
13	55	M	Subtotal gastectomy: PC in greater omentum, all small intestine serosa and transvers colon, Jan 2005.
14	58	M	Gastroenteroanastomosis + enteroenteroanastomisis, tumourgrowth to pancreas, PC in colon serosa + meso, Apr 2006. Withdrawal of informed concent three weeks after inclusion: chemotherapy beside the protocol.
15	72	M	Gastroscopy: prox. strictured tumour, CT: PC in greater omentum + paraaortic lymph nodes, Dec 2006
16	60	M	Gastroscopy: large tumour, CT: generally thick gastric wall + PC on right urether, Mar 2007
17	74	M	Gastroscopy: generally strictured tumour, CT: enlarged lymph nodes close to gastric great curvature + paraaortic lymph nodes, Feb - Mar 2007
18	66	M	Gastectomy + PC in colon meso, Jun 2005
19	76	M	Subtotal gastectomy, R1-resection (not radical at duodenum), pT2N0M0, Nov 2001. Ultrasonic guided autopsy: PC, Dec 2005. CT: tumour at pancreas with growth into large vessels + tumour dorsal of v. porta, Feb 2006.
20	40	F	Gastectomy (pT2bN2M0), no PC, Sep 2005. Expl. laparotomy: pelvic PC + ascites, May 2007. CRS + HIPEC Oct 2007. CT + Scint: skeletal met., Jan 2008 (also in a review seen at CT scan Sep 2007).

PC, peritoneal carcinomatosis.

Table III. Surgical procedures, tumour burden, completeness of surgical resection, preoperative and perioperative chemotherapy treatment for 10 patients in the CRS + HIPEC + EPIC group.

Pat.	1^st preop chemo	Cycles (number)	Length (months)	2^nd preop chemo	Cycles (number)	Length (months)	CRS	PCI	CC	HIPEC	EPIC
1	Irinotecan + Nordic FLv	6	3	–	–	–	AP, TGE, SE, SCE, SOE, PP	5	0	Cisplatin + Doxorubicin	5 days 5FU/LV
2	Irinotecan + Nordic FLv	7	3	–	–	–	AP, AWR, TGE, SE, SCE	14	0	Oxaliplatin	1 day 5FU/LV
3	Irinotecan + Nordic FLv	6	3	–	–	–	AP, LDR, RDR, TGE, SE, PTE, RCE, SCE, SOE, PP	10	0	Cisplatin + Doxorubicin	3 days 5FU/LV
4	Irinotecan + Nordic FLv	6	3	–	–	–	AP, TGE, SE, PP	5	1	Cisplatin + Doxorubicin	5 days paclitaxel
5	Irinotecan + Nordic FLv	6	3	–	–	–	AP, LDR, RDR, CE, SGE, AE, PP,	15	0	Cisplatin + Doxorubicin	5 days 5FU/LV
6	Docetaxel/5FU/LV + Irinotecan/5FU/LV	4 Doce + 4 Irino + 4 Doce	2+ 2+ 2	FLOX	7	3	AP, AWR, LDR, RDR, CE, TGE, SE, SBR, RCE, PCE, PCE, PP, SS	22	0	Cisplatin + Doxorubicin	5 days 5FU/LV
7	Irinotekan + Nordic FLv	7	3	Irinotekan + Nordic FLv	3-4	1,5 - 2	L, GS	md	Failure site: small bowel	No HIPEC	No EPIC
8	EOX	3	3	–	–	–	L	19	Failure site: small bowel	No HIPEC	No EPIC
9	EOX	4	4	–	–	–	AP, LDR, RDR, TGE, SE	6	0	Oxaliplatin	No EPIC
10	FOLFIRI	5	2	–	–	–	No operation	–	–	No HIPEC	No EPIC

CRS, cytoreductive surgery; PCI, Peritoneal Cancer Index; CC, Completeness of Cytoreduction score; HIPEC, hyperthermic intraperitoneal chemotherapy; EPIC, early postoperative intraperitoneal chemotherapy; FLv, sequential 5 fluorouracil/leucovorin 5FU/LV, 5 fluorouracil/leucovorin; AP, anterior peritonectomy; AWR, abdominal wall resection; LDR, left diaphragm peritonectomy; RDR, right diaphragm peritonectomy; CE, cholecystectomy; TGE, total gastrectomy; SGE, subtotal gastrectomy; SE, splenectomy; PTE, pancreatic tail ectomy; SBR, small bowel resection; AE, appendectomy; PCE, partial colectomy; RCE, right hemicolectomy; LCE, left hemicolectomy; SOE, salpingo-ofoorectomy; PCE, partial cystectomy; PP, pelvic peritonectomy, L = laparotomy; GS, gastrostomy; md, missing data; SS, sigmoideostomy.

Table IV. Treatment characteristics of the 10 patients in the systemic chemotherapy treatment group.

Pat.	Surgery before inclusion (type)	Surgery before inclusion (months)	Chemotherapy drugs during GA-TAC study (number of cycles)
11	TGE, SE L	4 2	Docetaxel/5FU/LV (4) + Irinotecan/5FU/LV (4)
12	TGE, SE	20	Docetaxel/5FU/LV (4) + Irinotecan/5FU/LV (1)
13	SGE	1	Docetaxel/5FU/LV (1)
14	GE	1	Docetaxel/5FU/LV (4) + Irinotecan/5FU/LV (4)
15	No surgery	–	Docetaxel/5FU/LV (4) + Irinotecan/5FU/LV (4)
16	No surgery	–	Docetaxel/5FU/LV (4) + Irinotecan/5FU/LV (3)
17	No surgery	–	Docetaxel/5FU/LV (4) + Irinotecan/5FU/LV (4)
18	TGE	2	Docetaxel/5FU/LV (4) + Irinotecan/5FU/LV (2)
19	SGE, CE	51	Docetaxel/5FU/LV (4) + Irinotecan/5FU/LV (4)
20	TGE, SE L L	4 7 0	Docetaxel/5FU/LV (4) + Irinotecan/5FU/LV (4)

5FU/LV, 5 fluorouracil/leucovorin; TGE, total gastrectomy; SGE, subtotal gastrectomy; GE, gastrojejunostomy + enteroenterostomy; SE, splenectomy; L = laparotomy; CE, cholecystectomy.

Table V. Costs collected in the study.

Outpatient physician visits (primary care, surgical, oncology etc)	PAC insertions	Chemotherapy (high-cost only)
Gastroscopies	PAC removals	Antibiotics (high-cost only)
Broncoscopies	Other surgical interventions	Phlebographies
CT (thorax, abdominal, head etc)	Hours in postoperative unit	MRI
Endoscopies	Hours in ICU care	X-rays
Laparoscopies	ICU drugs	Pulmonary angiographies
PET investigations	CT (thorax, abdominal)	Oesophagus stents
Ultrasounds	ECG	Days of rehabilitation
Minutes of anaesthesia	Radiotherapy	Dietician visit
Minutes of surgical time	Almoner visits	Disposables
Days at wards (surgical, oncology etc)	ECO	Spirometries

PAC, Porth-a-Cath; CT, computer tomography; MRI, magnetic resonance image; ICU, intensive care unit; PET, positron emission tomography; ECG, electrocardiography; ECO, echocardiography.

Figure 1. Overall survival in the CRS + HIPEC + EPIC group and systemic chemotherapy treated group. CRS, cytoreductive surgery; HIPEC, hyperthermic intraperitoneal chemotherapy; EPIC, early postoperative intraperitoneal chemotherapy; Systemic chemo, systemic chemotherapy treated group.

Table VI. Cost per life-years gained and per QALY gained.

	CRS + HIPEC + EPIC	Chemotherapy	Difference
Cost ($)	145 728	59 314	86 414
Life-years	1.45	0.93	0.52
QALYs	1.27	0.77	0.49
Cost per life-years gained ($)			166 716
Cost per QALY gained ($)			175 164

QALY, quality-adjusted life-years; CRS, cytoreductive surgery; HIPEC, hyperthermic intraperitoneal chemotherapy.

Figure 2. Mean costs for the CRS + HIPEC + EPIC group and systemic chemotherapy treated group. CRS, cytoreductive surgery; HIPEC, hyperthermic intraperitoneal chemotherapy; EPIC, early postoperative intraperitoneal chemotherapy.

Table VII. Main drivers of the cost during the treatment period.

Cost drivers	CRS + HIPEC + EPIC (% of total costs)	Chemotherapy (% of total costs)
Neoadjuvant chemotherapy (medicals)	$6300 (4%)	–
Surgical procedure	$29 300 (20%)	–
Associated intensive care	$24 100 (17%)	–
Chemotherapy (medicals)	–	$8700 (15%)
Associated visits	–	$5500 (9%)