Neoadjuvant chemoradiotherapy with capecitabine followed by laparoscopic resection in locally advanced tumors of middle and low rectum – Toxicity and complications of the treatment

Aims

The aim of this prospective study is to elucidate feasibility of protocol of neoadjuvant concomitant radiochemotherapy with capecitabine and long course radiotherapy with subsequent laparoscopic rectal resection. We assessed treatment toxicity, downstaging rate, pathological response to the neoadjuvant treatment, surgery complications, rate of conversions and sphincter-preserving surgical procedures, and intraoperative and early postoperative complications too.

Methods

We acquired data of 78 patients from 1 January 2005 to 31 December 2007 with a locally advanced rectal cancer in our study. All patients were indicated for the neoadjuvant concomitant chemoradiotherapy due to locally advanced tumor (T3 or T4) or lymph nodes involvement suspicion (N+). Both radiotherapy (to pelvic region) and chemotherapy (capecitabine) were administered. Rectal tumors were localized within 12 cm from the anocutaneous verge. The average follow-up time was 23.9 months.

Results

All patients completed their treatment according to the planned regimen and dose. The surgery was performed laparoscopicaly within 4–8 weeks following the concomitant chemoradiotherapy – in 17% cases was converted into conventional surgery. Downstaging was achieved in 69% of patients, pathological complete response in 10%, histologically negative lymph nodes were documented in 58% of patients. Grade 3 toxicity of the concomitant chemoradiotherapy was present in 3%; grade 2 in 29% of patients, particularly skin and gastrointestinal form. Intraoperative and early postoperative complications of the surgery were 18%. Re-operation was needed in 5% cases.

Conclusions

We demonstrated safety and low toxicity of the concomitant chemoradiotherapy with capecitabine.     

Neoadjuvant chemoradiotherapy and multivisceral resection for primary locally advanced adherent colon cancer: A single institution experience

Background

Although there is an extensive body of literature on the role of neoadjuvant chemoradiotherapy (CRT) in the management of rectal cancer, its role in primary locally advanced adherent colon cancer (LAACC) is unclear.

Objective

To analyzed the outcomes of neoadjuvant CRT and multivisceral resection in the management of LAACC patietns.

Methods

We retrospectively reviewed our institutional Colorectal Carcinoma Database for 33 patients with potentially resectable, non-metastatic primary LAACC who received neoadjuvant CRT followed by multivisceral resection. CRT consisted of external beam radiation (45–50 Gy in 25 daily fractions) and concurrent 5-FU infusion (225 mg/m²/day).

Results

There were 21 males and 12 females. Median age was 64 (31–83) and median follow-up was 36 months. All patients had microscopically clear resection margins (R0). Complete pathologic response was documented in 1 patient (3%) and 66% had ypT4b disease. Post-operative complications were observed in 36% of patients with no 30-day mortality. The 3-year overall survival and 3-year disease-free survival were 85.9% and 73.7% respectively. Two patients developed a local recurrence.

Conclusions

Neoadjuvant CRT and en-bloc multivisceral resection may result in high rates of R0 resection and excellent local control with acceptable morbidity and mortality in selected patients with LAACC.     

Cetuximab in combination with chemoradiotherapy in Chinese patients with non-resectable,locally advanced esophageal squamous cell carcinoma: A prospective,multicenter phase II trail

Background and purpose

This multicenter phase II trial investigated cetuximab combined with chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC).

Material and methods

Eligible patients with non-resectable, locally-advanced ESCC received cetuximab 400 mg/m² loading dose on day 1; and on day 1 of the 2nd–7th weeks: cetuximab 250 mg/m², paclitaxel 45 mg/m², and cisplatin 20 mg/m², concurrent with 59.4 Gy/33 fractions of radiation therapy. Primary endpoint was clinical response rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and KRAS status.

Results

Of 55 patients enrolled, 45 completed therapy. Forty-four patients had a clinical response: 29 complete response and 15 partial response. One-year PFS and OS of 45 evaluable patients were 84.23% and 93.33%, respectively, and 2-year PFS and OS were 74.87% and 80.00%, respectively. Non-hematologic adverse events were generally grade 1 or 2; primarily rash (92.7%), mucositis (45.5%), fatigue (41.8%), and nausea (38.2%). Grade 3 hematologic adverse events included neutropenia (32.7%) and anemia (1.8%). No KRAS mutations were identified in 50 evaluated samples.

Conclusions

Cetuximab can be safely administered with chemoradiotherapy to patients with locally-advanced ESCC and may improve clinical response rate.     

A phase II study of cetuximab,capecitabine and radiotherapy in neoadjuvant treatment of patients with locally advanced resectable rectal cancer

Background

Neoadjuvant chemoradiotherapy (CRT) reduces local tumor recurrence in locally advanced rectal cancer (LARC). This phase II study assessed neoadjuvant cetuximab with capecitabine-based CRT in LARC.

Methods

Patients with stage II/III LARC received capecitabine 1250 mg/m² twice daily for 2 weeks followed by intravenous cetuximab 400 mg/m² at week 3, then weekly intravenous 250 mg/m² cetuximab plus CRT including capecitabine 825 mg/m² twice daily (including weekends during radiotherapy) with radiotherapy of 45 Gy (25 × 1.8 Gy), 5 days a week for 5 weeks. Total mesorectal excision was scheduled 4–6 weeks following completion of CRT. The primary endpoint was pathological complete response (pCR).

Results

Thirty-seven patients were eligible for safety and efficacy. TMN staging at baseline was: T4N2, 11%; T3N2, 40%; T2N2, 3%; T3N1, 35%; T2N1, 3% and T3N0 8%. The most common adverse events included, grade 1/2 acneiform skin rash (86%), and grade 3 radiodermatitis, (16%), diarrhea (11%) and hypersensitivity (5%). pCR was achieved in 3 patients (8%). Overall-, T- and N-downstaging rates were 73%, 57% and 81% respectively. Total sphincter preservation rate was 76%, and 53% in 17 patients whose tumors were located within 5 cm from the anal verge. Non-fatal perioperative complications occurred in 13 patients (35%) with delayed wound healing occurring in 6 patients (16%). One death was recorded due to sepsis following colonic necrosis.

Conclusion

Neoadjuvant cetuximab with capecitabine-based CRT is tolerable in patients with resectable LARC. Whilst the pCR rate was similar to recent reports, a high pathological downstaging rate was achieved.     

Patent blue staining as a method to improve lymph node detection in rectal cancer following neoadjuvant treatment

Introduction

Lymph node involvement is one of the most important prognostic factors in rectal cancer. After neoadjuvant treatment the number of retrieved lymph nodes is often reported to be low which impairs reliable tumour staging. This study examines the effect of patent blue staining on the number of harvested lymph nodes and evaluates whether a higher number of retrieved lymph nodes is of prognostic significance.

Patients and methods

Between March 2007 and December 2010, 295 consecutive patients with locally advanced rectal cancer following neoadjuvant treatment were included. Specimens were either not stained (NB), injected with patent blue into the mesorectum (MB) or directly into the inferior mesenteric artery (AB). Data were retrieved from a prospective database.

Results

The number of evaluated lymph nodes was significantly higher in the stained specimens: mean 6.8 in the NB group (n = 89), 11.5 in the MB group (n = 86) and 17.4 in the AB group (n = 106) (p < 0.001). The percentage of patients with a minimum of 12 lymph nodes increased from 15.5% (NB) to 44.2% (MB) to 74.5% (AB) (p < 0.001). The three-year cancer specific survival for the lymph node ratio (LNR) was 95% (0), 94.4% (0.01–0.1), 80.1% (0.11–0.4) and 63.7% (0.41–1).

Conclusion

The use of patent blue in patients who underwent rectal cancer surgery after neoadjuvant treatment significantly enhanced lymph node harvest. Injection into the inferior mesenteric artery was most effective. This relatively simple and generally applicable method can help to improve lymph node detection which lowers the LNR and allows adequate tumour staging.     

Thymidylate synthase genotypes and tumour regression in stage II/III rectal cancer patients after neoadjuvant fluorouracil-based chemoradiation

Purpose

According to the CAO-/ARO-/AIO-94 trial of the German Rectal Cancer Study Group, pre-operative 5-fluorouracil (5-FU)-based long-term chemoradiotherapy (CT/RT) is recommended for patients with rectal cancer UICC stage II/III. However, despite the local benefit of neoadjuvant treatment, the overall prognostic value remains uncertain in comparison to adjuvant CT/RT. We assessed the impact of standardized pre-operative CT/RT and intratumoural mRNA levels and polymorphisms of the TS gene on histopathological tumour regression.

Patients and methods

40 patients with rectal cancer UICC stage II/III, receiving pre-operative 5-FU-based CT/RT followed by standardized surgery, including total mesorectal excision, were investigated. TS gene expression and TS polymorphisms of surgical specimens were correlated with the grade of histopathological tumour regression (0–4). Patients achieved regression grades 2–4 were determined as responders.

Results

TS polymorphisms (5′-28 bp repeat + G/C SNP and TS1494del6) could be determined in 39/40 (97.5%) and in 38/40 (95%) patients, respectively. Quantification of TS mRNA expression was successful in 36/40 (90%) patients. There was a highly significant linkage disequilibrium between 5′- and 3′-TS polymorphisms (p = 0.0013). Interestingly, the majority of patients (82.1%) with 5′-TS genotypes known to be associated with low mRNA expression (2R/2R, 2R/3RC, 3RC/3RC) also possessed the TS1494del6 +6 bp/+6 bp genotype correlating with high TS mRNA expression. TS1494del6 polymorphism was significantly associated with TS mRNA expression. Patients with TS1494del6 −6 bp/−6 bp or −6 bp/+6 bp genotypes showed significantly lower mean TS mRNA expression with 0.55 (range:0.33;0.84) as compared to +6 bp homozygotes with a mean expression of 0.90 (range:0.20;1.91) (p = 0.025). Furthermore, all patients with TS 3′-UTR −6 bp/−6 bp or −6 bp/+6 bp genotype (11/11) were responders as compared to only 20/26 (77%) of patients with TS 3′-UTR +6 bp/+6 bp genotype (p = 0.082). TS 5′-polymorphisms were not associated with neither tumour regression nor gene expression.

Conclusion

Our data suggest that the TS1494del6 polymorphism may be an important predictor for histopathological tumour regression in UICC II/III rectal cancer patients receiving neoadjuvant 5-FU-based CT/RT.     

Two-week course of preoperative chemoradiotherapy followed by delayed surgery for rectal cancer: A phase II multi-institutional clinical trial (KROG 11-02)

Purpose

The aim of this study was to evaluate the efficacy and safety of a two-week schedule of radiotherapy with oral capecitabine in locally advanced rectal cancer.

Methods and materials

Eighty patients with rectal cancer located in the mid to low rectum, staged cT3-4N0-2M0, were prospectively enrolled. They underwent preoperative chemoradiotherapy and delayed surgery 6–8 weeks after the completion of radiation therapy. A radiation dose of 33 Gy in 10 fractions was delivered to the pelvis for 2 weeks. One cycle of oral capecitabine was administered at a dose of 1650 mg/m²/day during radiotherapy. Tumor response and toxicity were the study endpoints. This study was registered at ClinicalTrials.gov (number, NCT01431599).

Results

All included patients underwent total mesorectal excisions including 12 cases of robot assisted surgery and 50 cases of laparoscopic surgery. Of the 80 patients, 27 (33.8%) achieved downstaging (ypT0-2N0) of a rectal tumor and 11 (13.8%) had a pathologically complete response (ypCR). Downstaging rates were 45% for T classification and 65% for N classification. Sphincter saving was achieved in 73 (91.3%) of the 80 patients. Of the 80 patients, 3 (3.8%) experienced grade 3 hematologic toxicity, and 2 (2.5%) had grade 3 postoperative complications such as ileus and wound dehiscence. There was no grade 4 toxicity.

Conclusion

A two-week schedule of radiotherapy with oral capecitabine in locally advanced rectal cancer patients showed low toxicity profiles and promising results in terms of tumor response.     

Rigid sigmoidoscopy and MRI are not interchangeable in determining the position of rectal cancers

Purpose

1) To analyse for interchangeability of rigid sigmoidoscopy and MRI in determining the distance from anus to tumour, and to determine if anterior/posterior location influences this difference. 2) To analyse the effect of preoperative chemo-radiotherapy on the distance from anus to tumour.

Methods

Retrospective investigation of endoscopy reports and MRI series of 144 consecutive patients operated for rectal cancer.

Results

The mean distance from the anal verge to the tumour measured by sigmoidoscopy was 82 mm and by MRI 61 mm (p < 0.01). For tumours in the anterior quadrant this difference was 30 mm and for tumours located in the posterior quadrant only 12 mm. The distributions of the cancers as low, middle and high differ by more than 10% between the two methods. The coefficient of correlation between measurements was 0.9 but the variation was not acceptable. The length of the tumours decreased by 16 mm after neoadjuvant treatment, but the distance from tumour to anus increased by only 4 mm.

Conclusion

1) MRI and sigmoidoscopy are not interchangeable in determining the distance from anus to tumour simply by correcting for the length of the anal canal. It has not been determined if measurements from MRI or sigmoidoscopy are more accurate, but current evidence concerning the effect of neoadjuvant irradiation at different positions in the rectum is based upon rigid sigmoidoscopy. 2) The gain in tumour free distance above the anus induced by neoadjuvant treatment is small. Facilitation of sphincter-saving surgery should not be an argument for neoadjuvant treatment.     

Medium-term results of neoadjuvant systemic chemotherapy using irinotecan, 5-fluorouracil,and leucovorin in patients with locally advanced rectal cancer

Aims

The aim of this study was to evaluate the usefulness of neoadjuvant systemic chemotherapy using irinotecan, 5-FU, and leucovorin (LV) for the treatment of locally advanced rectal cancer, which was a powerful ploychemotherapy in those days in Japan.

Methods

Between 2001 and 2004, 26 patients with T3 or T4 and N0-2 non-metastatic resectable rectal cancer were selectively enrolled in this study. Neoadjuvant chemotherapy consisted of two cycles of irinotecan (80 mg/m²), 5-FU (500 mg/m²), and LV (250 mg/m²) on days 1, 8, and 15 for 4 weeks. Surgical resection was performed in all the patients 2–4 weeks after the completion of chemotherapy.

Results

Overall down-staging was observed in 15 patients. T level and N level down-staging were observed in 12 and 13 patients, respectively. A pathological complete response was observed in one patients. The median follow-up period was 75 months (range, 8–97 months). Recurrences occurred in 5 patients including pelvic relapses in 3 and distant metastases in 2. The 5-year relapse-free and overall survival rates were 74% and 84%, respectively.

Conclusions

Neoadjuvant systemic chemotherapy comprised of a combination of multi-drugs as irinotecan, 5-FU, and LV may be beneficial to the prognoses of patients with locally advanced rectal cancer.     

Perioperative use of the LiMON method of indocyanine green elimination measurement for the prediction and early detection of post-hepatectomy liver failure

Introduction

A non-invasive liver function monitoring system, the LiMON^®, has been developed that measures indocyanine green (ICG) elimination by pulse spectrophotometry. The aim was to assess the relationship between pre and post-operative ICG plasma disappearance rate (ICG PDR %/min) values and the onset of post-hepatectomy liver dysfunction.

Methods

37 patients scheduled for major liver resections were selected. None had chronic liver disease. IGC PDR was measured preoperatively and on days 1, five and 10 postoperatively. On the same day, serum liver function tests were measured.

Results

The median preoperative and post-operative day 1 ICG PDR for the patients who developed liver dysfunction was significantly lower compared to those who did not (p = 0.044, p = 0.014). Significant correlation was found between ICG PDR measurement taken on postoperative day 1 and bilirubin level on day 1 (p = 0.002), 5 (p =<0.001) and 10 (p = 0.001). The same was true for ICG PDR on post-operative day 1 and albumin level on day 5 and 10 (p = 0.003, p < 0.001).

Discussion

LiMON ICG PDR measured by pulse spectophotometry is a quick, non-invasive and reliable liver function test in patients undergoing liver resection that aids in the prediction and early detection of post-hepatectomy liver dysfunction.     

Neoadjuvant bevacizumab,docetaxel and capecitabine combination therapy for HER2/neu-negative invasive breast cancer: Efficacy and safety in a phase II pilot study

Purpose

To evaluate the triplet combination of bevacizumab, capecitabine and docetaxel (XTA) as neoadjuvant therapy for breast cancer.

Experimental design

Patients with invasive, HER2-negative, nonmetastatic breast cancer (T2–4c >2 cm) and no prior systemic therapy received six 21-day cycles of XTA (bevacizumab 15 mg/kg, day 1, cycles 1–5; docetaxel 75 mg/m², day 1 of each cycle; capecitabine 950 mg/m² twice daily for 14 days of each cycle). Patients underwent surgery 2–4 weeks after completing XTA, followed by radiotherapy, chemotherapy and hormone therapy according to institution guidelines. Pathologic complete response (pCR), the primary endpoint, was defined as no evidence of invasive tumour in the final surgical sample. Secondary endpoints included rates of clinical response and breast-conserving surgery and safety.

Results

Median age of the 18 enrolled patients was 48 years (range 34–69). Most patients (72%) received six cycles of neoadjuvant therapy. pCR rate was 22% (95% confidence interval [CI]: 6–48). Nine of the patients without pCR achieved clinical partial response, giving a 72% overall clinical response rate (95% CI: 47–90). Fifteen patients underwent breast-conserving surgery (83%; 95% CI: 59–96). One additional patient had breast-conserving surgery, followed by mastectomy 1 month later. The remaining 2 patients underwent modified radical mastectomy. XTA was reasonably well tolerated, with no unexpected toxicities or treatment-related deaths.

Conclusions

The 22% pCR rate in a HER2-negative population suggests that addition of bevacizumab increases the activity of neoadjuvant capecitabine–docetaxel. Further evaluation of this regimen in early breast cancer is recommended.     

Addition of bevacizumab to XELOX induction therapy plus concomitant capecitabine-based chemoradiotherapy in magnetic resonance imaging-defined poor-prognosis locally advanced rectal cancer: the AVACROSS study

Background.

Concomitant chemoradiotherapy followed by total mesorectal excision is standard treatment for locally advanced rectal cancer. This approach, however, focuses on local disease control and delays systemic treatment. Induction chemotherapy has the advantage of earlier administration of systemic therapy and may improve distant control. The objective of the current study was to assess the efficacy and toxicity of adding bevacizumab to induction chemotherapy followed by preoperative bevacizumab-based chemoradiotherapy in patients with locally advanced rectal cancer.

Patients and Methods.

Eligible patients had high-risk rectal adenocarcinoma defined by magnetic resonance imaging criteria. Treatment consisted of four 21-day cycles of bevacizumab (7.5 mg/kg) and XELOX (capecitabine plus oxaliplatin), followed by concomitant radiotherapy (50.4 Gy) plus bevacizumab (5 mg/kg every 2 weeks) and capecitabine (825 mg/m² twice daily on days 1–15). Surgery was scheduled for 6–8 weeks after chemoradiotherapy. The primary endpoint was pathologic complete response (pCR).

Results.

Between July 2007 and July 2008, 47 patients were recruited. Among 45 patients who underwent surgery, pCR was achieved in 16 patients (36%; 95% confidence interval: 22.29%–51.27%), and an additional 17 patients (38%) had Dworak tumor regression grade 3. R0 resection was performed in 44 patients (98%). Most grade 3/4 adverse events occurred during the induction phase and included diarrhea (11%), asthenia (4%), neutropenia (6%), and thrombocytopenia (4%). Eleven patients (24%) required surgical reintervention.

Conclusions.

Addition of bevacizumab to induction chemotherapy and chemoradiotherapy is feasible, with impressive activity and manageable toxicity. However, caution is recommended regarding surgical complications.     

Long-term results of concurrent radiotherapy and UFT in patients with locally advanced pancreatic cancer

Background

Definition and treatment options for locally advanced non-resectable pancreatic cancer (LAPC) vary. Treatment options range from palliative chemotherapy to chemoradiotherapy (CRT). Several studies have shown that a number of patients become resectable after complementary treatment prior to surgery.

Methods

From 2001 to 2005, 63 consecutive patients with unresectable LAPC received CRT. CRT was given at a dose of 50 Gy/27 fractions, combined with UFT (300 mg/m²/day) and folinic acid. Re-evaluation of resectability was planned 4-6 weeks after completion of CRT.

Results

Fifty-eight patients completed all 27 treatment fractions. Toxicity was generally mild, with 18 patients experiencing CTCAE grade 3 or worse acute reactions. One patient died following a treatment-related infection. Two patients developed grade 4 upper GI bleeding. Median survival was 10.6 (8-13) months. Eleven patients underwent resection, leading to a resection rate of 17%, and a median survival of 46 (23-nr) months. All 11 patients had a R0 resection. Median survival for the patients not resected was 8.8 (8-12) months.

Conclusion

CRT with 50 Gy combined with UFT, is a well-tolerated and effective treatment for patients with LAPC. R0 resection was possible in 17% leading to a long median survival of 46 months in resected patients.     

Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer: Analysis of therapeutic results in 112 cases

Purpose

To evaluate the therapeutic results and rate of organ preservation in patients with stage III or IV oral cancer treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy.

Materials and methods

One hundred and twelve patients with stage III and IV oral squamous cell carcinoma underwent intra-arterial chemoradiotherapy. Catheterization from the superficial temporal and occipital arteries was performed. Treatment consisted of superselective intra-arterial chemotherapy (docetaxel, total 60 mg/m², cisplatin, total 150 mg/m²) and daily concurrent radiotherapy (total of 60 Gy) for 6 weeks.

Results

The median follow-up for all patients was 46.2 months (range, 10–76 months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 98 (87.5%) of 112 cases. Five-year survival and local control rates were 71.3% and 79.3%, respectively. Grade 3 or 4 toxicities included mucositis in 92.0%, neutropenia in 30.4%, dermatitis in 28.6%, anemia in 26.8%, and thrombocytopenia in 7.1% of patients. Grade 3 toxicities included dysphagia in 72.3%, nausea/vomiting in 21.4%, fever in 8.0%, and renal failure in 0.9% of patients.

Conclusion

Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer provided good overall survival and local control.     

Lymph node yield in rectal cancer surgery: Effect of preoperative chemoradiotherapy

Aim

Adequate lymph node resection in rectal cancer is important for staging and local control. This study aims to verify the effect of neoadjuvant chemoradiation, as well as some clinicopathological features, on the yield of lymph nodes in rectal carcinoma.

Methods

Data on consecutive patients who had total mesorectal excision for rectal adenocarcinoma at a single cancer center between January 2003 and July 2008 were reviewed. No patient had any prior pelvic surgery or radiotherapy. Patients had neoadjuvant chemoradiotherapy if they were stage II or III.

Results

A total of 116 patients were included. The mean age was 53 years (range 29–83). Fifty-nine patients (51%) received neoadjuvant therapy before resection. The mean number of lymph nodes removed was 18 (range 4–67) per specimen. There was less lymph node yield in patients who received neoadjuvant therapy (16 vs. 19, p = 0.008). Only 64% of patients who had preoperative therapy had 12 lymph nodes or more in the specimen as opposed to 88% of those who had surgery upfront (p = 0.003). Other factors associated with lower lymph node yield included: female sex (p = 0.03) and tumour location in the lower rectum (p = 0.002). Age, tumour stage and grade, type of operation and surgical delay did not affect the number of lymph nodes removed.

Conclusion

Preoperative chemoradiotherapy for rectal cancer results in reduction in lymph node yield. Female sex and lower rectal tumours are also associated with retrieval of fewer lymph nodes.     

Ex vivo sentinel lymph node “mapping” in colorectal cancer

Background

The purpose of this study was to evaluate the feasibility and reliability of ex vivo sentinel lymph node mapping in patients with colorectal cancer.

Methods

In the period January–June 2006, 44 consecutive patients underwent curative surgery for colorectal cancer. In patients with colon and rectal cancer, 0.5–2 ml of Patent Blue Dye was injected submucosally. The injection sites where then gently massaged for 5 min.

Results

In 96% of the patients with colon cancer and 94% of the patients with rectal cancer, at least one sentinel lymph node was found.There were no patients with a false negative sentinel node. The sensitivity was 100% with a negative predictive value of 100%. In 19% of the patients with colon cancer and 18% of the patients with rectal cancer the sentinel node was the exclusive site of lymph node metastases. After additional sectioning and staining, 7 of the 23 patients (30%) with a Dukes B colorectal cancer were upstaged.

Conclusion

The technique of ex vivo sentinel lymph node mapping is technically feasible with high sensitivity, high negative predictive value and a high rate of upstaging.The next step is to investigate, if detection of micro-metastases is associated with decreased survival and/or increased local recurrence rates.     

Neo-adjuvant chemoradiotherapy and multivisceral resection to optimize R0 resection of locally recurrent adherent colon cancer

Background

Neo-adjuvant chemoradiotherapy reduces local recurrence in rectal cancer, but there is a paucity of evidence regarding its role for colon cancer. The aim of this study was to evaluate the feasibility and outcomes of a neo-adjuvant chemoradiotherapy (NCRT) approach for locally recurrent adherent colon cancer (LRACC).

Methods

All patients with non-metastatic LRACC treated with NCRT and multi-visceral resection (MVR) from January 2000 to July 2010 were included. The primary outcome was the rate of R0 resection (negative microscopic margins). Secondary outcomes were toxicities, post-operative morbidity and mortality, local recurrence, overall survival (OS) and disease-free survival (DFS).

Results

Fifteen patients were identified. Nine primary cancers were located in the sigmoid and 4 in the left colon. Patients were treated with 45–50 Gy in 25 daily fractions and concurrent 5-FU infusion (225 mg/m²/day). En-bloc MVR included between 2 and 5 adjacent organs/structures. All but two resulted in R0 resection. One patient had a complete pathologic response and one had minimal residual tumour cells in the resected specimen. Post-operative major morbidity was 33.3%. No mortality occurred. At a median follow-up of 54 months, there were 2 local, 1 regional, and 2 distant lung recurrences. No grade 3 or 4 acute or late toxicities were observed. 5-year OS and DFS were 90.0% and 63.5% respectively.

Conclusions

NCRT followed by MVR is a feasible option for the treatment of highly selected LRACC to achieve R0 resection, while maintaining acceptable treatment toxicity. Short-term oncological results appear satisfactory, including good local control.     

A randomized phase II study of cisplatin/5-FU concurrent chemoradiotherapy for esophageal cancer: Short-term infusion versus protracted infusion chemotherapy (KROSG0101/JROSG021)

Purpose

A randomized phase II study was conducted to compare the toxicity and efficacy of combining short-term chemotherapy (CT) or protracted CT with radiotherapy (RT) for esophageal cancer.

Materials and methods

Eligible patients were <75 years and with performance status (PS) of 0-2, and had stages II-IVA esophageal cancer. Two cycles of cisplatin 70 mg/m² for 1 day and 5FU 700 mg/m² for 5 days (arm A) or cisplatin 7 mg/m² for 10 days and 5FU 250 mg/m² for 14 days (arm B) were given with RT of 60 Gy/30 fractions/7 weeks (1-week split).

Results

Of 91 patients enrolled, 46 were randomized to arm A and 45 to arm B. Two cycles of CT were given concurrently with RT for 89% in arm A and for 71% in arm B with significant difference (P = .031). The 2- and 5-year overall survival rates for arm A were 46% and 35%, while those for arm B were 44% and 24%, respectively, without significant difference. The 2- and 5-year progression-free survival rates for arm A were 30% and 30%, while those for arm B were 29% and 12%, respectively.

Conclusions

Protracted infusion CT with RT provides no advantage over standard short-term infusion CT with RT for esophageal cancer.     

Phase II study of oral S-1 plus cisplatin with bevacizumab for advanced non-squamous non-small cell lung cancer

Background

We conducted a phase II study to evaluate the efficacy and safety of S-1 plus cisplatin with bevacizumab followed by maintenance bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC).

Patients and methods

Chemotherapy-naïve patients received S-1 plus cisplatin with bevacizumab. S-1 (80 mg/m²) was administered orally twice daily for 14 days, cisplatin (60 mg/m²) on day 1, and bevacizumab (15 mg/kg) on day 1 and every 3 weeks for 4–6 cycles. Patients with an objective response or stable disease received maintenance bevacizumab every 3 weeks until disease progression.

Results

Thirty patients were enrolled in this study. The median number of chemotherapy was four (range, 1–6 cycles), and the median number of bevacizumab alone was three (range, 1–31 cycles). The grade 3/4 toxicities were neutropaenia (23%), thrombocytopaenia (10%), febrile neutropaenia (3%), hypertension (17%), pneumonia (7%), and bowel perforation (3%). The objective response rate was 71% (95% CI, 55–88%) for a disease control rate of 100%. The median progression-free and overall survival times were 7.0 months and 20.0 months, respectively.

Conclusions

S-1 plus cisplatin with bevacizumab is an active and well-tolerated regimen in patients with chemotherapy-naïve non-squamous NSCLC.     

Axillary recurrence after a tumour-negative sentinel node biopsy in breast cancer patients: A systematic review and meta-analysis of the literature

Background

Sentinel node biopsy became the standard of care before consensus on the technique was reached and without randomized studies having shown a similar or decreased axillary recurrence rate. The purpose of this study was to evaluate studies reporting on patients with a negative sentinel node biopsy.

Methods

We performed a systematic review and meta-analysis of the literature for studies concerning clinically node-negative breast cancer patients with a tumour-negative sentinel node biopsy and no subsequent axillary node dissection. The axillary recurrence rate was determined, as well as the sensitivity of the sentinel node procedure and the differences in lymphatic mapping techniques.

Results

Forty-eight studies concerning 14?959 sentinel node-negative breast cancer patients followed for a median of 34 months were selected. Sixty-seven patients developed an axillary recurrence, resulting in a recurrence rate of 0.3%. The sensitivity of the sentinel node biopsy was 100%. Uni- and multivariable variable analyses showed that the lowest recurrence rates were reported in studies performed in cancer centres, in studies that described the use of ^99mTc-sulphur colloid, and also when investigators used the superficial injection technique or evaluated the harvested sentinel nodes with haematoxylin–eosin and immunohistochemistry staining (p < 0.01).

Conclusions

In this systematic literature review, the axillary recurrence rate in sentinel node-negative patients is 0.3%, which is well within the desired range. The median sensitivity of the procedure appears to be as high as 100%. The recurrence rate is influenced by the differences in the lymphatic mapping technique.