18FDG-PET evaluation correlates better than CT with pathological response in a metastatic colon cancer patient treated with bevacizumab-based therapy

Around 20-30% of patients with hepatic metastasis from colorectal cancer can undergo liver resection, but the increased response rate obtained with the addition of monoclonal antibodies to chemotherapy regimens could result in a higher rate of liver surgery. In this report we describe the case of a patient who underwent a liver resection after neoadjuvant treatment with capecitabine, oxaliplatin and bevacizumab and who achieved a complete pathological response of the liver metastasis. A preoperative CT scan demonstrated a partial response to the treatment while 18FDG-PET scan correctly evaluated the complete pathological response in the liver and detected an active interaortocaval lymph node metastasis. New specific studies are required to evaluate the imaging response in metastatic colorectal cancer patients especially after treatment with new, targeted agents.     

Detecting para-aortic lymph nodal metastasis by positron emission tomography of 18F-fluorodeoxyglucose in advanced cervical cancer with negative magnetic resonance imaging findings

The patient's prognosis is significantly related to para-aortic lymph node metastasis in advanced cervical cancer. Magnetic resonance imaging (MRI) has been widely performed to detect lymph node metastasis with a variable sensitivity. Therefore, in this prospective study, we evaluated FDG-PET to detec para-aortic lymph nodal metastasis in locally advanced cervical carcinoma with negative MRI findings. Forty-two women with advanced cervical cancer and negative abdominal MRI findings were included in this study. Para-aortic lymph node metastases were confirmed according to para-aortic lymph-adenectomy findings. Para-aortic lymphadenectomy findings showed 12 patients with para-aortic lymph nodal metastasis. Two patients had false-negative and 1 patient had false-positive FDG-PET findings. The FDG-PET showed sensitivity of 83.3%, specificity of 96.7%, and accuracy of 92.9%. As assessment of para-aortic lymph node metastases may be essential for therapy planning, FDG-PET is an alternative tool to detect para-aortic lymph node metastases in advanced cervical cancer with negative MRI findings.     

Gastric cancer with para-aortic lymph node metastases: do not miss a chance of cure!

This letter to editor is a comment to the paper by Wang et al. entitled: “A phase II trial of Xeloda and oxaliplatin (XELOX) neo-adjuvant chemotherapy followed by surgery for advanced gastric cancer patients with para-aortic lymph node metastasis”. In a phase II trial, patients with primary gastric cancer and clinical involvement of para-aortic nodes (PAN) were treated by neo-adjuvant chemotherapy with capecitabine and oxaliplatin combination, and responders were then submitted to gastrectomy with D2 lymphadenectomy. The diagnostic and therapeutic approach adopted in this protocol is discussed, with special reference to the potential limits of computed tomography scan for the clinical diagnosis of PAN metastases (false positive results), and the opportunity to perform a D2 plus para-aortic lymphadenectomy, to further increase the chance of cure in patients with suspected PAN metastases.     

Phase I trial of hepatic arterial infusion (HAI) of floxuridine with modified oxaliplatin, 5-fluorouracil and leucovorin (m-FOLFOX6) in Chinese patients with unresectable liver metastases from colorectal cancer

Purpose

Chemoradiotherapy followed by total mesorectal excision (TME) is the standard treatment for locally advanced rectal cancer. Although this approach decreases the risk of local recurrence, pelvic radiation is associated with long-term morbidity and delays systemic treatment. We conducted this study to evaluate the feasibility of neoadjuvant capecitabine and oxaliplatin (XELOX) plus bevacizumab as a treatment for high-risk localized rectal cancer.

Methods

Patients with T4 or lymph node-positive rectal cancer were treated with three cycles of XELOX plus bevacizumab and one additional cycle of XELOX. This was followed by TME performed 3–8 weeks after the last chemotherapy session.

Results

Twenty-five patients were recruited between December 2009 and November 2011. In seven of the patients (28.0 %), grade 3–4 adverse events occurred. After preoperative chemotherapy, the frequency of tumor (T) downstaging was 69.6 %, and that of lymph node (N) downstaging was 78.9 %. Seven patients discontinued the treatment after 2–3 cycles of XELOX plus bevacizumab. The frequency of subsequent surgery was 92 %, and all patients underwent R0 resections. Postoperative complications occurred in six patients (26.1 %). One patient achieved a pathological complete response (pCR) for the primary tumor and lymph nodes, whereas an additional four patients achieved near-pCR. After a median follow-up of 31 months, five patients displayed metastatic progression, including one who suffered local recurrence.

Conclusions

XELOX plus bevacizumab followed by TME is feasible for high-risk localized rectal cancer, as it achieves good tumor regression and causes manageable toxicity.     

Complete response to preoperative chemoradiotherapy in highly advanced gastric adenocarcinoma

This report presents a case of highly advanced gastric cancer that achieved a histologically complete response (CR) to preoperative chemoradiotherapy with S-1 plus low-dose Cisplatin. A 60-year-old male patient underwent FDG positron emission tomography (PET) during a routine health examination. The patient was found to have swollen paraaortic lymph nodes. Shortly thereafter, he was diagnosed with gastric carcinoma with a type 2 tumor in the antrum with paraaortic lymph node metastases based on FDG-PET, endoscopic examination and abdominal computed tomography. After the completion of chemoradiation therapy (CRT), the tumor and the paraaortic lymph node metastases disappeared. The patient underwent surgery 5 wk after the completion of CRT, including a subtotal gastrectomy with Roux-en-Y reconstruction, D3 lymph node dissection and a left adrenalectomy. No cancer cells were detected in the resected specimen either in the primary lesion or lymph nodes, thus confirming a pathologically CR to CRT (CR grade 3). The patient has been stable and well without any evidence of recurrence for 48 mo after surgery. Such a preoperative CRT regimen might therefore be very effective for treatment of some advanced gastric cancers.     

Two cases of ovarian metastasis of colon cancer

CASE 1: A 45-year-old female underwent sigmoidectomy, simple total hysterectomy and bilateral adnexotomy for sigmoid colon cancer and a right ovarian metastasis in December 2007. As adjuvant chemotherapy, S-1 was conducted for six months. She remains disease-free for 38 months after the surgery. CASE 2: A 61-year-old female underwent simple total hysterectomy and bilateral adnexotomy for bilateral ovarian tumors following the surgery for colon cancer, metastatic liver cancer and gastric cancer in January 2010. As adjuvant chemotherapy, capecitabine was administered seven times. Five months after the last surgery, para-aortic lymph node recurrence was diagnosed. FOLFIRI/panitumumab therapy was maintained. For both of the two cases in immune-staining, CK20 staining was positive, and CK7 staining was negative. Ovarian tumors were diagnosed as metastasis from colon cancer. Ovarian metastasis of colon cancer is a relatively rare event, but a long-term survival case has been reported by multimodality therapy including surgery.     

奥沙利铂联合卡培他滨治疗胃癌术后淋巴转移的近期疗效

[目的]探讨奥沙利铂联合卡培他滨治疗胃癌手术后淋巴转移的近期疗效。[方法]48例胃癌手术后淋巴转移患者采用奥沙利铂联合卡培他滨方案治疗共176个周期。[结果]CR4例，PR28例，NC12例和PD4例，总有效率（CR＋PR）为66．7％f32／48）。中位缓解期6．2个月，中位生存期12.3个月，1年生存率为60．5％，临床受益者共44例（90．5％）。毒副反应可耐受，无患者因为毒副反应终止治疗，无相关死亡出现。[结论]奥沙利铂加卡培他滨方案治疗胃癌手术后淋巴转移疗效较好。毒副反应能够耐受。可作为一线方案在胃癌手术后淋巴转移的病人中应用。     

A case successfully treated with abdominoperineal resection after preoperative chemoradiation therapy for anal cancer

A 46-year-old female was diagnosed with anal squamous cell carcinoma. Chemoradiation therapy was administered for a first-line therapy. Two courses of enforced 5-FU/MMC combination therapy were administered along with radiotherapy (60 Gy). This chemoradiation therapy had complete response. However, three months after, anal cancer had a local recurrence. Since there was no distant metastasis, abdoninoperineal resection was performed. No complications were observed after the operation. We conclude that abdominoperineal resection may be effective in the treatment of anal cancer in cases which the local recurrence was observed after chemoradiation therapy.     

A clinical case of lymph node recurrence after resection of gastric cancer successfully treated by combination chemotherapy with irinotecan and cisplatin

A 60-year-old female who was diagnosed as gastric cancer underwent distal gastrectomy and received adjuvant chemotherapy (S-1 therapy). After 6 months, the tumor marker (CEA) was elevated. CT revealed para-aortic lymph nodes enlargement. Lymph node metastasis was confirmed. The patient was administered combination chemotherapy with irinotecan (CPT-11) and cisplatin (CDDP) Seven months later, CT revealed lymph node metastasis had disappeared. After judgment of complete response (CR), we continued the treatment for 22 months. The patient was followed without any recurrence in May 2010.     

Preoperative and adjuvant treatment of localized rectal cancer

Although postoperative chemoradiation has a proven role in the treatment of stage II to III localized rectal cancer, recent trials have demonstrated the role of preoperative chemoradiation. A recent randomized trial has shown that preoperative chemoradiation yields higher rates of local control and sphincter preservation and lower rates of toxicity, compared with postoperative chemoradiation. Randomized trials have also shown that preoperative chemoradiation yields higher rates of pathologic complete response and local control, compared with radiotherapy alone. In this article, we review recent trials on preoperative and adjuvant therapy of localized rectal cancer. The roles of newer agents, such as capecitabine, oxaliplatin, and bevacizumab, are also discussed, and other key issues in the treatment of localized rectal cancer are reviewed.     

A Successfully Resected Case of Recurrent Lung and Liver Metastases of Rectal Cancer Treated with XELIRI + Bevacizumab Therapy

It has been reported that many colorectal cancer (CRC) patients with synchronous or metachronous liver metastases underwent surgery subsequent to neoadjuvant combination chemotherapy with folinic acid, fluorouracil, and oxaliplatin (FOLFOX), folinic acid, fluorouracil, and irinotecan (FOLFIRI), or capecitabine and oxaliplatin (XELOX). However, there are very few reports of the use of capecitabine and irinotecan (XELIRI). We herein report a successfully resected case of recurrent lung and liver metastases of rectal cancer treated with combination chemotherapy with XELIRI + bevacizumab (BV) therapy. A 63-year-old male developed recurrence of a solitary nodule in the right lower lobe of the lung and multiple liver metastases after low anterior resection for rectal cancer 1 year previously. Partial resection of the right lower lobe of the lung was performed and treatment with XELIRI + BV was initiated. A computed tomography scan revealed a reduction in tumor size without any new lesions after four cycles of XELIRI + BV therapy. Partial hepatectomy of S1, S5, and S7 was safely performed. The patient is now undergoing adjuvant chemotherapy and has been free from recurrence for 18 months following surgery. There are only few studies with relatively low patient numbers reporting on the outcome after resection of both pulmonary and hepatic metastases of CRC. We therefore report a patient who underwent sequential resection of pulmonary and hepatic metastases with XELIRI + BV therapy.Key words: Colorectal cancer, Liver metastasis, XELIRI     

三维适形放疗同步奥沙利铂加卡培他滨术前治疗Ⅱ～Ⅲ期直肠癌的疗效观察

目的 探讨Ⅱ～Ⅲ期直肠癌应用奥沙利铂联合卡培他滨术前同步放化疗的临床疗效及毒副反应。方法 收集大连医科大学附属第二医院放疗科2008年至2012年收治的经病理组织学证实的Ⅱ～Ⅲ期直肠癌患者104例,术前均行同步放化疗。三维适形放疗：1.8 Gy／次,DT 50.4 Gy／28次。同步化疗方案：奥沙利铂50 mg／m2,每周1次,共5次;卡培他滨1650 mg／（m2·d）,d1～d35。同步放化疗结束后8周进行手术,术后完成6个月的FOLFOX 6方案全身化疗。观察并随访术前同步放化疗后疗效及不良反应。结果 同步放化疗后肿瘤降期率为55.8％（58／104）,术后完全缓解（CR）22例,部分缓解（PR） 67例,稳定（SD） 15例,有效率（RR）为85.6％（89／104）。总体保肛率为78.8％（82／104）。不良反应主要为腹泻、恶心、呕吐、骨髓抑制及口腔炎等,仅1例4级不良反应发生,无放化疗相关死亡。3年生存率、无病生存率、远处转移率及局部复发率分别为90.3％、74.0％、24.0％和3.9％。结论 Ⅱ～Ⅲ期直肠癌奥沙利铂联合卡培他滨术前同步放化疗能降低肿瘤分期,提高肿瘤病理完全缓解率,且不良反应可耐受,局部控制可,但并未明显降低远处转移率,其结果仍需长期随访。     

A case of recurrent sigmoid colon cancer with adrenal and para-aortic lymph node metastasis successfully treated by operation and chemotherapy

We report a case of 57-year-old woman suffering from advanced sigmoid colon cancer with adrenal and para-aortic lymph node recurrence. Sigmoidectomy was performed for sigmoid colon cancer in January 2002. Pathological staging was Stage II (pT3, pN0, pM0, Cur A). She received a UFT + CPT-11 regimen as preoperative chemotherapy for liver metastasis (S2, S7) from December 2002. A partial liver resection (S2, S7) was performed for liver metastasis in July 2003, and the UFT + CPT-11 was introduced as adjuvant chemotherapy. However, adrenal and para-aortic lymph node recurrence was detected in February 2007, and mFOLFOX6 was performed as preoperative chemotherapy. Right adrenalectomy and para-aortic lymph node dissection was performed in July 2007. mFOLFOX6 as postoperative chemotherapy was done, mFOLFOX6 + bevacizumab was started because of CEA increase. The chemotherapy was performed for 23 courses and temporarily stopped due to adverse reactions, such as peripheral neuropathy (grade 2), general fatigue (grade 1), and nausea (grade 1). She had no recurrence for almost 3 years after a resection of adrenal and para-aortic lymph node metastasis.     

Efficacy of chemotherapy combined with dissection of para-aortic lymph node metastasis following gastric cancer surgery -- case report

A 64-year-old man visited our hospital complaining of epigastric pain. An upper gastrointestinal endoscopy revealed a type 2 gastric cancer at the lower portion of the lesser curvature of the stomach. We performed a distal gastrectomy with D2 dissection. The histopathological diagnosis was well-differentiated tubular adenocarcinoma, mp, ly2, v0, n2(+), No. 11p(1/ 1), Stage III a.We used postoperative chemotherapy with a combination of S-1(80 mg/body)and low-dose cisplatin(10mg/ body × 10 days). After 1 course, we continued only S-1(80 mg/body)for 3 weeks followed by a 2-week interval. About 1 year after the operation, the CEA value was abnormally high. An abdominal CT scan showed a marked swelling of the paraaortic lymph node. The patient was then treated with the same protocol of S-1 and cisplatin again, but the CEA value did not decrease; therefore, a para-aortic lymph node dissection(No. 16a2b1 latero)was performed. Although the CEA value had decreased to normal, a few months later it was high again, and so we increased the S-1 dosage from 80 mg/body to 100mg/ body. But 6 months after the first para-aortic lymph node dissection, positron emission tomography(PET)revealed a swelling of paraaortic lymph node below the first recurrence site again. We changed the postoperative chemotherapy from S-1 and cisplatin to S-1(100mg/body)and irinotecan(80 mg/m2 day 1, 8). Since the CEA value was not decreased, we performed a second para-aortic lymph node dissection(No. 16b1b2 latero)13 months after the first dissection. The patient is presently alive with no signs of recurrence after over 1. 5 years. Para-aortic lymph node dissection combined with postoperative chemotherapy appeared to be effective for para-aortic lymph node metastasis in this case.     

Phase 2 study of preoperative radiation with concurrent capecitabine,oxaliplatin, and bevacizumab followed by surgery and postoperative 5‐fluorouracil,leucovorin, oxaliplatin (FOLFOX), and bevacizumab in patients with locally advanced rectal cancer: ECOG 3204

BACKGROUND:

Recent studies have demonstrated the feasibility of combining oxaliplatin with 5‐fluorouracil (5‐FU) or capecitibine and radiation therapy. The addition of bevacizumab to chemotherapy improves overall survival for metastatic disease. We initiated a phase 2 trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy followed by surgery and postoperative 5‐FU, leucovorin, oxaliplatin (FOLFOX) and bevacizumab for locally advanced rectal cancer.

METHODS:

Fifty‐seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled. Preoperative treatment was capecitabine (825 mg/m² twice daily from Monday to Friday), oxaliplatin (50 mg/m² weekly), bevacizumab (5 mg/kg on days 1, 15, 29), and radiation therapy (50.4 Gy). Surgery was performed by 6 weeks after neoadjuvant therapy. Beginning 8 to 12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles.

RESULTS:

Fifty‐four of 57 enrolled patients were eligible. Forty‐nine (91%) patients completed preoperative therapy and underwent surgery. Nine patients (17%; 90% confidence interval, 9%‐27%) achieved pathologic complete response. Thirty‐two patients (59%) experienced pathologic tumor downstaging, and 53% and 15% of patients experienced worst grade 3 and grade 4 acute toxicity, respectively. Forty‐seven percent of patients who underwent surgery experienced a surgical complication.

CONCLUSIONS:

The primary endpoint of a 30% pathologic complete response rate was not reached; however, the majority of patients experienced pathologic downstaging with this regimen. Increased wound‐healing delays and complications may have been related to the addition of bevacizumab, oxaliplatin, or both. Continued observation of these patients will establish the long‐term morbidity and efficacy of this combined modality approach. Cancer 2013. © 2012 American Cancer Society.     

Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: Phase I trial results

PURPOSE: The overexpression of vascular endothelial growth factor (VEGF) is associated with poor outcomes in colorectal cancer patients. Bevacizumab, a VEGF inhibitor, enhances the effects of chemotherapy and radiation therapy on tumor cytotoxicity in preclinical models, including colorectal cancer. A Phase I trial was undertaken to evaluate the combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in patients with rectal cancer. METHODS AND MATERIALS: Patients with pathologically confirmed adenocarcinoma of the rectum were eligible. Pretreatment staging included computerized tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external beam radiation therapy (EBRT) to the tumor in 28 fractions. Capecitabine, oxaliplatin, and bevacizumab were administered concurrently with radiation therapy. After EBRT completion, patients were restaged and evaluated for surgery. Primary endpoints included the determination of dose-limiting toxicity and a recommended Phase II dose, non dose-limiting toxicity, and preliminary radiographic and pathologic response rates. RESULTS: Eleven patients were enrolled. All were evaluable for toxicity and efficacy. Dose level 2 was associated with unacceptable toxicity (primarily diarrhea). Dose level 1 had an acceptable toxicity profile. The recommended Phase II dose in our study was bevacizumab 15 mg/kg Day 1 + 10 mg/kg Days 8 and 22, oxaliplatin 50 mg/m2 weekly, and capecitabine 625 mg/m2 bid during radiation days. Six patients had clinical responses. Two patients had a pathologic complete response, and 3 had microscopic disease only. One patient experienced a postoperative abscess, one a syncopal episode during adjuvant chemotherapy, and one a subclinical myocardial infarction during adjuvant chemotherapy. CONCLUSIONS: The combination of bevacizumab, capecitabine, oxaliplatin, and radiation therapy in rectal cancer was tolerable, with encouraging response rates. Further investigation with this regimen is being pursued in a Phase II setting.     

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 gastric cancer patient with marked para-aortic lymph node metastasis surviving more than 10 years after aggressive operation and repeated EAP chemotherapy

The high incidence of side effects for EAP (etoposide, adriamycin, cisplatin) combination chemotherapy led to the recent decline in its use. However, we report herein the long-term disease-free survival of a woman following postoperative EAP therapy. A 57-year-old woman was referred to our hospital because of general malaise. X-ray and endoscopic examination revealed a Borrmann type 3 gastric cancer. Preoperative computed tomography and ultrasonography revealed multiple para-aortic lymph node swellings. The patient simultaneously underwent subtotal gastrectomy and splenectomy, and complete para-aortic lymph node dissection. Histopathological tests revealed that the tumor was a poorly differentiated adenocarcinoma with 35 metastatic para-aortic lymph nodes. The patient was treated with 2 cycles of EAP therapy. After discharge, swelling in one para-aortic lymph node was detected. Following three subsequent cycles of EAP therapy, the swollen lymph node disappeared and the patient has remained disease free for 10 years. This case illustrates that aggressive surgery followed by repeated courses of EAP therapy can produce excellent clinical outcomes.     

胃癌腹主动脉旁淋巴结清扫术（附26例临床分析）

目的:分析胃癌腹主动脉旁淋巴结(No.16)转移规律。方法:对本院2004年10月至2005年10月间实施的26例胃癌No.16淋巴结清扫术的临床病理资料作回顾性分析。结果:全组26例均行胃癌No.16(16a2区及16b1区)淋巴清扫术,术后恢复良好,无吻合口漏及手术死亡。乳糜腹1例,术中大出血1例。共切除No.16淋巴结79枚,平均3枚/例,发现肿瘤转移12枚,转移度为15.19%;4例患者发现No.16转移,转移率为15%。结论:No.16淋巴结作为胃癌区域淋巴液引流的终末汇聚地,有较高的转移率。不论是为了手术后正确分期还是提高治疗效果腹主动脉旁淋巴结清扫都是必要的,而且手术也是安全的。