Curative-intent stereotactic body radiation therapy for residual breast cancer liver metastasis after systemic chemotherapy.

Liver metastases from breast cancer are generally treated with systemic therapy such as chemotherapy or hormonotherapy. However, local treatment options such as resection, radiofrequency ablation (RFA), and radiotherapy can also be considered to treat oligometastases. We report the case of a 45-year-old female treated with stereotactic body radiotherapy (SBRT) after chemotherapy against a solitary liver metastasis from primary breast cancer. A liver metastasis with diameter of 35 mm developed 3.5 years after surgery for primary breast cancer in 2004. Fourteen courses of triweekly docetaxel treatments considerably decreased the metastatic lesion, but there still remained a tiny lesion radiographically. Chemotherapy was stopped because of the side-effects of docetaxel, and then SBRT was selected for additional treatment, aiming at complete cure of metastasis. X-ray irradiation (52.8 Gy/4 fractions) was applied to the remaining metastatic lesion, and magnetic resonance imaging (MRI) showed no evidence of residual tumor 4 months after irradiation. Neither regrowth nor recurrences have been found until now, 24 months after SBRT. SBRT for oligometastases of breast cancer may be one of the possible curative-intent options, being less invasive than surgical resection or RFA.

[HER2 testing for advanced recurrent gastric cancer in a general hospital].

The Japanese gastric cancer treatment guidelines(published as a web supplement for version 3)recommend the implementation of HER2 testing prior to the selection of chemotherapy. Since we had not yet implemented HER2 immunohistochemistry(IHC)methods for gastric cancer, we tried to compare the HER2 testing results from a reference laboratory(ref lab) and our hospital(in-house). The HER2 concordance rates were calculated between the results from in-house and ref lab using 26 cases(31 samples)which were from patients with advanced, metastatic unresectable, or Stage IV resectable gastric cancer. The HER2 expression(in-house/ref lab)was distributed as follows: negative/negative, 18 cases; negative/equivocal, 2 cases; negative/positive, 1 case;equivocal/equivocal, 2 cases; and positive/positive, 3 cases. The concordance rate was 88. 4%(23/26), and the mismatch rate was 11. 6%(3/26)between in-house and ref lab. Although IHC test results with in-house and ref lab had been generally consistent, it is still necessary to improve and standardize diagnostic accuracy in the near future.

[Stereotactic radiotherapy for metastatic liver cancer].

Twenty cases (27 therapeutic sites/30 nodules) of metastatic liver cancer treated with stereotactic radiotherapy (SRT)were analyzed. The original sites of cancer were colorectal(8 cases), breast(4 cases), stomach(3 cases), esophagus(2 cases), and other organs (3 cases). SRT was performed with 52.8 Gy·4 fr·-1·wk-1. The response rate was 78%, including complete response (CR) at 8 sites, partial response (PR) at 10 sites, stable disease (SD) at 2 sites, progressive disease(PD) at 3 sites, and not detected(ND) at 4 sites, thus demonstrating a potent local therapeutic effect. Ten patients survived for more than 1 year, 8 patients survived for 2 years, and 4 died before 6 months. Clinical analysis suggests that the ideal indications for SRT are patients with a solitary nodule and without extrahepatic disease who have undergone systemic chemotherapy.

[Effects of stereotactic radiotherapy targeting for recurrent gastric cancer].

We report the effects of stereotactic radiotherapy (SRT) targeting for distant solitary metastases from gastric cancer that were uncontrollable with chemotherapy. SRT(52.8 Gy per 4 fractions) was performed in 3 patients with liver metastasis and 1 patient with lung metastasis. Although SRT showed no effect in the patient with lung metastasis, complete remission from liver metastasis with cystic change was observed in all 3 patients. One patient died due to multiple liver metastasis, and the other 2 patients are alive 27 and 41 months after SRT without liver metastasis. Although pneumothorax and pleural effusion were recognized in 1 case, grade 3 or 4 adverse events were not recognized in all 4 cases. SRT showed excellent local therapeutic effects without serious complications, suggesting that this is an effective treatment for localized metastasis from gastric cancer.

[A case of paraaortic lymph node metastasis of gastric cancer resistant to chemotherapy successfully treated with chemoradiation therapy].

We report a case of recurrent gastric cancer with paraaortic lymph nodes (No.16LNs) that was effectively controlled with chemoradiation therapy. A 63-year-old man underwent distal gastrectomy, cholecystectomy, and D2 dissection in July 2004 for advanced gastric cancer in the lower third area that was diagnosed as moderately differentiated stage II adenocarcinoma [T1(SM), N2, H0, P0, CY0, M0]. He suffered from No.16LNs metastasis with serum CEA elevation in October 2007, and therefore, 4 courses of S-1, followed by 3 courses of CPT-11 as second-line treatment, 14 courses of docetaxel as third-line treatment, and 15 courses of paclitaxel+cisplatin as fourth-line chemotherapy, were administrated. Enlargement of No.16LNs with serum CEA elevation was observed in October 2010. Other metastases were not observed, and hence, chemoradiotherapy (CRT; S-1: 80 mg/body+total of 65 Gy per 26 Fr) for No.16LNs was performed. A partial response and reduction of serum CEA level were noted, and the patient is alive with no sign of progression 18 months after CRT. Grade 1 adverse events including anemia, fatigue, and anorexia were recognized. It is thought that chemoradiation therapy is an effective treatment for localized LN metastasis originating from gastric cancer resistant to chemotherapy.

[A case of advanced gastric cancer with splenic vein thrombus successfully treated with S-1 plus CPT-11 neoadjuvant chemotherapy].

A 63-year-old male admitted for hematemesis was diagnosed with type 3 advanced gastric cancer located in the upper and middle body of the stomach in an endoscopic examination. Abdominal computed tomography demonstrated lymph nodes metastasis and a splenic vein thrombus. Since curative resection was not deemed possible, we performed neoadjuvant chemotherapy using S-1 (120 mg, day 1-21) plus CPT-11 (135 mg, day 1 and 15) except for down-staging. After 4 courses of chemotherapy, gastric tumor and metastatic lymph nodes were reduced in size and the splenic vein thrombus was disappeared, and then total gastrectomy was performed (tub2, T2 (MP) N0 H0 M0 P0 CY0, Stage IB). S-1 medication was applied as adjuvant chemotherapy. Forty months passed from the operation, the patient remains alive with no signs of relapse.

[Complete remission of liver metastasis from gall bladder carcinoma after stereotactic radiotherapy-a case report].

A 75-year-old man was diagnosed as gall bladder carcinoma by postoperative histological examination following laparoscopic cholecystectomy. He underwent the second surgery of resection of liver bed and port sites with lymph node dissection. Isolated hepatic metastasis of 20 mm in diameter was found in S4/8 by MRI 18 months postoperatively, and stereotactic radiotherapy (52.8 Gy/4 Fr) was done for the metastatic lesion. The lesion could not be detected by CT 7 months after the radiotherapy, and thereafter no local recurrence has been observed for 24 months. However, lymph node metastasis of #9 was diagnosed 31 months postoperatively. Liniac radiotherapy (60 Gy/20 Fr)was performed and stable disease has been obtained for 9 months. The patient is alive at present of 43 months after surgery without any other site of the disease, and his quality of life is well maintained. Stereotactic radiotherapy showed an excellent local therapeutic effect without any serious complications, suggesting that this is a potent modality for isolated liver metastasis of gall bladder carcinoma.

[A case of recurrent gastric cancer successfully treated with radiation therapy].

We report a case of recurrent gastric cancer that was effectively controlled with radiation therapy. A 63-year-old man underwent total gastrectomy, cholecystectomy and D2 dissection in February 2006 for early gastric cancer in the upper third area that was diagnosed with papillary adenocarcinoma and Stage IA (T1 (SM), N0, H0, P0, CY0, M0). He underwent lateral segmentectomy of the liver for liver metastasis of S2/3. He suffered from No. 12 lymph node(LN)metastasis in February 2009, so CPT-11, next to S-1, was administered. Portal tumor thrombosis (PTT) and liver S8 metastasis were observed in September 2009. First, chemoradiotherapy (CRT) ( S-1 80 mg/body+total of 65 Gy per 26 Fr) for #12 LN and PTT was performed and, in turn, stereotactic radiation therapy (SRT: total of 52.8 Gy per 4 Fr) was performed. A complete response in all of tumors was noted and he was presently alive with no sign of recurrence after 19 months after CRT and SRT. Grade 3 or 4 adverse events were not recognized. It is thought that radiation therapy is one of effective treatments for localized metastasis from gastric cancer.

[Re-resection for local recurrence in the remnant pancreas after pancreaticoduodenectomy for pancreatic cancer- a case report].

A 70-year-old female suffered from jaundice was admitted to our hospital for a tumor in the pancreas head. CA19-9 and DUPAN-2 levels were increased in laboratory test. Enhanced abdominal computed tomography (CT) scan revealed a low density area of pancreas head. Cytology of pancreatic juice was performed by ERCP, and malignant cells were detected. Pancreaticoduodenectomy was performed under a diagnosis of pancreatic cancer (T3N1M0, stage III). Despite of adjuvant chemotherapy (gemcitabine) after surgery, CT scan revealed a low density area in the cut end of remnant pancreas at 3 months, which was accompanied with elevation of and CA19-9 and DUPAN-2 levels. We diagnosed as a recurrent pancreatic cancer of remnant pancreas without any other side of recurrence and re-resection was performed. Because of chylous ascites and depression following a second surgery, postoperative adjuvant chemotherapy could not be started. Re-recurrence was detected at 3 months after the second surgery, and she died 6 months after the surgery. Remnant or repeated pancreatectomy for local recurrent pancreatic carcinomas is extremely rare with limited number of cases reported in the literature. We report our experience, and discuss the significance of re-resection for recurrence of remnant pancreas.

A phase I study of bi-weekly docetaxel for recurrent or advanced gastric cancer patients whose disease progressed by prior chemotherapy.

OBJECTIVE: Although docetaxel is active against gastric cancer, Grade 3 or 4 neutropenia occurs in the majority of patients in Japan when administered at 60 mg/m(2) every 3 weeks. To determine a more convenient and tolerable schedule than the tri-weekly schedule, we conducted a dose-escalation study of bi-weekly docetaxel. In this study, we investigated the maximum-tolerated dose and recommended dose. METHODS: Patients with advanced gastric cancer who had received prior chemotherapy were enrolled between April 2004 and March 2007. This study was designed to evaluate the escalated dose of docetaxel starting at 35 mg/m(2) (Level 1) given every 2 weeks. The dose was escalated in a stepwise fashion to 40 mg/m(2) (Level 2), 45 mg/m(2) (Level 3) and 50 mg/m(2) (Level 4). RESULTS: Fifteen patients completed at least two cycles of the therapy. Three episodes of Grade 3 neutropenia occurred in all patients and Grade 4 neutropenia was observed at Level 4 in six patients. Grade 3 or 4 thrombocytopenia and anemia were not observed. Grade 3 aspartate aminotransferase/alanine aminotransferase elevation (n= 1) and Grade 3 stomatitis (n = 1) were noted at Level 4. There was no other Grade 3 or 4 non-hematologic toxicity. The definition of dose-limiting toxicities of this docetaxel schedule at Level 4 are Grade 4 neutropenia, Grade 3 aspartate aminotransferase/alanine aminotransferase elevation and Grade 3 stomatitis. CONCLUSIONS: The maximum-tolerated dose of docetaxel when administrated following the bi-weekly schedule was 50 mg/m(2) and the recommended dose was 45 mg/m(2). Bi-weekly administration of docetaxel may provide a better tolerated and efficacious use in gastric cancer.

Paclitaxel-resistant recurrent gastric cancer responsive to docetaxel: a case report.

We present the case of a 58-year-old man who underwent distal gastrectomy for Stage III A advanced gastric cancer, identified as poorly-differentiated adenocarcinoma. He was diagnosed with recurrent peritoneal metastasis 11 months after surgery. S-1(80mg/m / 2)was administered as first-line chemotherapy, followed by weekly paclitaxel(80mg/m2)as secondline chemotherapy. Although a partial response was obtained, a peritoneal tumor in the upper abdomen, ascites, and an elevation in the serum carcinoembryonic antigen(CEA)level were observed. As the tumor proved resistant to paclitaxel, making the treatment ineffective, bi-weekly docetaxel(45mg/m2)was initiated. The tumor showed a partial response, the ascites disappeared, and the serum CEA level decreased. The time to progression was seven months until the appearance of ileus and ascites due to tumor re-growth. This paclitaxel-resistant gastric cancer with peritoneal recurrence proved responsive to docetaxel as third-line chemotherapy. Docetaxel may be active against gastric cancer that is resistant to paclitaxel because of the different effects of these two agents. Further clinical studies on the efficacy of docetaxel against paclitaxel-resistant gastric cancer are needed.

[A case of recurrent gastric cancer with lymph node metastasis successfully treated by CPT-11/CDDP therapy].

We report a case ofa 76-year-old man suffering from advanced gastric cancer with lymph node recurrence. Distal gastrectomy was performed for gastric cancer with pylorus stenosis in April 2001. Pathological staging was III A(T3, N1, M0, Cur B). He underwent outpatient treatment with oral administration of UFT 400mg/day as postoperative adjuvant chemotherapy, but stopped after two months because of loss of appetite and general fatigue. Partial liver resection(S4/5)was performed for liver metastasis(S4)in June 2002, and S-1 was administered 80mg/day as adjuvant chemotherapy. However, obstructive jaundice was detected for lymph node recurrence in March 2003, and conducted bile duct stent after PTCD. He started to undergo a biweekly combination chemotherapy of irinotecan (CPT-11)60mg/m / 2 and cisplatin(CDDP)30mg/m2. Three months later, the lymph node had decreased in size. We reduced this therapy, extended the interval, and discontinued it after 24 courses due to adverse reactions, such as leucopenia(grade 3)and general fatigue(grade 2). Afterward, he had no recurrence for over 5 years.

[Evaluation of hepatic arterial infusion chemotherapy using removable W-spiral catheter].

The authors analyzed the 62 patients who underwent hepatic arterial infusion (HAI) chemotherapy using W-spiral (WS) catheter. The catheter was successfully inserted into the hepatic artery without a coil fixation in 57 cases. After cessation of chemotherapy, the catheter was removed in 32 cases without difficulty, which resulted in improved patients' quality of life as well as preservation of patency of hepatic arteries. This catheter has a special shape-memory alloy in its tip, which allows preferable fixation without coils and removal of the catheter if desired. HAI using this catheter and subsequent removal of it is a reasonable strategy in the era with potent systemic chemotherapy.

[A case of advanced gastric cancer successfully treated with chemoradiotherapy targeting for recurrent lymph node metastasis].

The patient was a 75-year-old male, who was diagnosed with type 3 advanced gastric cancer and bulky lymph node metastasis. Two courses of neoadjuvant chemotherapy (S-1, CDDP) which showed a partial remission and distal gastrectomy were performed. Although he received S-1 medication as adjuvant chemotherapy, lymph node recurrence appeared 6 months after the operation. Radiation therapy at a total dose of 65 Gy (10MV X ray, 2.5 Gy/day × 26 Fr) selectively targeting for recurrent lymph node metastasis with S-1 medication were applied. There were no adverse effects during chemoradiation therapy and the metastatic node showed regression (30 mm to 15 mm). Sixteen months passed from chemoradiation, and the patient remains alive with no signs of relapse without any treatment after the chemoradiation. Therefore, our case suggests that chemoradiation therapy could be an effective treatment for recurrent lymph nodes metastasis in gastric cancer.

[A case of liver metastasis from gastric cancer treated with stereotactic radiation therapy].

We report a case of liver metastasis from gastric cancer that was effectively controlled with stereotactic radiation therapy (SRT). A 77-year-old man underwent total gastrectomy, splenectomy, cholecystectomy and D2 dissection in February 2007 for type 3 gastric cancer in the upper third area that was diagnosed well to moderately differentiated adenocarcinoma and Stage II (T3 (SE) N0 H0 P0 CY0 M0). He suffered from the liver and peritoneal metastases with ascites in December 2007, so S-1 was administered. Ascites was disappeared, but liver metastasis was enlarged. Therefore, SRT (total of 52.8 Gy per 4 fractions) was performed for the liver metastasis. A clear reduction in tumor size was noted and he was presently alive with no sign of recurrence after 2 years. Immediately after SRT, grade 3 neutropenia and grade 2 AST/ALT elevation were occurred. Grade 2 pneumothorax and pleural effusion were recognized in August 2009 as tardive adverse event. It is thought that SRT is one of effective treatments for liver metastasis from gastric cancer.

[Adjuvant chemotherapy with FOLFOX4 regimen after curative resection of liver metastases from colorectal cancer].

Only a partial benefit of adjuvant chemotherapy administered after curative resection of colorectal cancer (CRC) metastases has been demonstrated. We report here our experience of 7 cases that were administered FOLFOX4 regimen as adjuvant chemotherapy after a curative resection of liver metastases from CRC. Five patients received 6 cycles of FOLFOX4 after prophylactic hepatic arterial infusion of 5-FU, and 2 remaining patients simply received 8 cycles of FOLFOX4. All patients completed the planned cycles of FOLFOX4 without any dose reduction of oxaliplatin. No patients developed a severe adverse effect greater than grade 2 except for grade 3 neutropenia observed in 4 cases. Although lung metastases occurred in 2 cases 28.1 and 21.3 months after liver resection, respectively, all patients are alive after a median follow up of 23.5 months. Our experience indicates that adjuvant chemotherapy with six to eight cycles of FOLFOX4 regimen is safe with a high dose intensity of oxaliplatin and expected to provide a survival benefit.

[A case of successfully treated lower rectal cancer with both inguinal lymph nodes by chemoradiotherapy].

We report a case of successfully treated lower rectal cancer with both inguinal lymph nodes by chemoradiotherapy. A 59-year-old man presented with anal pain. A colonoscopy revealed primary rectal cancer. The histological diagnosis was well to moderately differentiated adenocarcinoma. A computed tomography showed metastases to pararectal, both inguinal lymph nodes and right external iliac. After a ileostomy construction was done, he was treated with intensity modulated radiotherapy (a total 50.4 Gy) and chemotherapy with FOLFOX. The primary tumor had completely disappeared, and metastases to lymph nodes showed a remarkable shrinkage after the chemoradiotherapy. Nine months after radiation therapy, however, multiple lung and liver metastases were observed by a computed tomography, which were treated by systemic chemotherapy with FOLFOX and bevacizumab. The primary tumor and metastases to lymph nodes are still controlled well for 2 years after the initial chemoradiotherapy.

[A complete response of locally-advanced poorly differentiated adenocarcinoma of the rectum to pre-operative chemo-radiation therapy].

A 71-year-old woman with peri-anal pain and anal bleeding was found to have a tumor in lower rectum in colonoscopic examination, which was histologically diagnosed as poorly differentiated adenocarcinoma. Computed tomography and magnetic resonance imaging showed a tumor 5 cm in diameter deeply infiltrating mesorectum, and swelling of intra-pelvic lymph nodes. At the first operation, infiltration of the tumor was so deep that a complete surgical resection was considered to be difficult, and only a sigmoid colostomy construction was done. After chemo-radiation therapy of 50.4 Gy and 5-FU plus levofolinate calcium (Isovorin) infusion, the tumor was reduced in size and lymph nodes were extremely decreased. The patient underwent an abdominoperinial resection 6 weeks after the end of chemo-radiation, and pathological examination revealed a complete replacement of tumor with necrosed tissue, and no viable tumor cell was found. Poorly differentiated adenocarcinoma of the colon is reported to be highly malignant and associated with poor prognosis. Preoperative chemo-radiation therapy can be a promising candidate for adjuvant treatment of locally-advanced poorly differentiated adenocarcinoma of the rectum.

[A case of successfully treated orbital metastasis from breast cancer by radiation therapy].

Orbital metastasis from breast cancer is relatively rare. We report a case of successfully treated orbital metastasis from breast cancer by radiation therapy. This 50-year-old female patient underwent a mastectomy (Bt+Ax) of her left breast in October 2000. The diagnosis was invasive lobular carcinoma, Stage IIB (T2N1M0). Retroperitoneal and bladder metastases were found five years after the operation, and chemohormonal therapy was done. Right orbital swelling appeared 8 months after chemohormonal therapy, and orbital metastasis from breast cancer was diagnosed by MRI. Radiation therapy (a total 30 Gy) was administrated, and the swelling disappeared. An MRI was performed 16 months after radiation therapy and did not detect any metastases. A complete response (CR) was achieved. No sign of recurrence was found, and a sufficient local control has remained for 2 years after radiation therapy.

[FOLFOX 4 in a patient with metastatic colorectal cancer on hemodialysis due to chronic renal failure].

A 68-year-old woman was on dialysis for the treatment of chronic renal failure. FOLFOX 4 therapy was performed following CPT-11+UFT+Leucovorin for liver metastasis after resection of cancer of the sigmoid colon. The dose of oxaliplatin was 40 mg/m2, while 5-FU was given as a bolus of 300 mg/m2, and a continuous intravenous infusion of 500 mg/m2. Hemodialysis was performed 1 hour after administration of oxaliplatin on day 1 and was repeated two days later after the completion of drug administration. Vomiting (grade 2),anorexia and leukopenia (both grade 3) were observed after the first treatment. A total of 4 courses were administered thereafter by reducing the dose of oxaliplatin to 32 mg/m2, the intravenous bolus of 5-FU to 240 mg/m2, and continuous infusion of 5-FU to 400 mg/m2. Measurement of drug concentrations showed that free platinum was immediately eliminated by dialysis. It was considered possible to safely perform FOLFOX 4 therapy in patients with chronic renal failure by reducing the doses and by providing dialysis. It is desirable to measure drug concentrations in these patients. Also,more cases should be monitored to investigate the safe dose,the blood drug concentration profile, and the accumulation of chemotherapy agents.