Predicting Pathological Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Using 18FDG-PET/CT

Background

Pathologic complete response (pCR) after neoadjuvant chemoradiation (CRT) has been observed in 15?C30% of patients with locally advanced rectal cancer (LARC). The objective of this study was to determine whether PET/CT can predict pCR and disease-free survival in patients receiving CRT with LARC.

Methods

This is a retrospective review of patients with EUS-staged T3?CT4, N?+?rectal tumors treated with CRT, who underwent pre/post-treatment PET/CT from 2002?C2009. All patients were treated with CRT and surgical resection. Standardized uptake value (SUV) of each tumor was recorded. Logistic regression was used to analyze the association of pre-CRT SUV, post-CRT SUV, %SUV change, and time between CRT and surgery, compared with pCR. Kaplan?CMeier estimation evaluated significant predictors of survival.

Results

Seventy patients (age 62?years; 42M:28F) with preoperative stage T3 (n?=?61) and T4 (n?=?9) underwent pre- and post-CRT PET/CT followed by surgery. The pCR rate was 26%. Median pre-CRT SUV was 10.8, whereas the median post-CRT SUV was 4 (P?=?0.001). Patients with pCR had a lower median post-CRT SUV compared with those without (2.7 vs. 4.5, P?=?0.01). Median SUV decrease was 63% (7.5?C95.5%) and predicted pCR (P?=?0.002). Patients with a pCR had a greater time interval between CRT and surgery (median, 58 vs. 50?days) than those without (P?=?0.02). Patients with post-CRT SUV?P?=?0.03). Patients with SUV decrease ??63% had improved overall survival at median follow-up of 40?months than those without (P?=?0.006).

Conclusions

PET/CT can predict response to CRT in patients with LARC. Posttreatment SUV, %SUV decrease, and greater time from CRT to surgery correlate with pCR. Post-CRT, SUV?相似文献   

REG I Expression Predicts Long-term Survival among Locally Advanced Thoracic Squamous Cell Esophageal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy Followed by Esophagectomy

Background The prognosis for patients with locally advanced thoracic esophageal cancer is extremely unfavorable. We have been administering neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy to these patients and studying whether REG I expression in untreated endoscopic biopsy specimens is predictive of patient responsiveness to CRT and/or survival after treatment.Methods Between 1992 and 2003, 47 patients with T4 (direct invasion of adjacent organs) thoracic esophageal cancers were administered neoadjuvant CRT followed by esophagectomy. REG I expression was assessed in untreated endoscopic biopsy specimens and correlated with clinical and histological responses and survival in 37 patients who had also undergone curative surgery.Results Among the 37 cases that received CRT followed by surgery, the therapeutic response rate for neoadjuvant CRT was 68%, and a complete histological response in resected specimens from the primary lesion was achieved in 8 (22%) patients. These clinical and histological responses to neoadjuvant CRT did not significantly correlate with survival, however. By contrast, 9 patients were judged REG-positive based on analysis of their untreated endoscopic biopsy specimens, and their cumulative survival rate was significantly higher than that of the 28 REG-negative patients (P = 0.0073). Univariate analysis showed REG I expression to be a prognostic factor (P = 0.0386) that increased the risk of death 8.4-fold.Conclusions Evaluation of REG I expression in untreated endoscopic biopsy specimens may provide a basis for new treatments of locally advanced thoracic squamous cell esophageal cancers.     

新辅助放化疗对直肠癌降期的影响

局部进展期直肠癌定义为距离肛缘≤12cm,局部分期T3～T4或任何T、N阳性,无远隔转移的直肠癌[1]。目前新辅助放化疗已成为局部进展期直肠癌的标准治疗。新辅助放化疗后的肿瘤消退,会导致临床降期和病理学的微观改变,这些改变对于外科治疗和患者的远期预后有重要的指导意义。     

Hemoglobin Level Influences Tumor Response and Survival After Neoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma

Background

Neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy confers a survival benefit on patients with esophageal cancer. However, nCRT might be less meaningful for poor responders. Thus, being able to predict responses would help ensure the selection of optimal therapy.

Methods

We reviewed data from 123 patients with esophageal squamous cell carcinoma (ESCC) who underwent nCRT that comprised concurrent radiation (40 Gy) and chemotherapy followed by esophagectomy. We assessed associations between clinical and blood data obtained before starting nCRT and the pathologic response.

Results

We compared good (Japan Esophageal Society response evaluation criteria grades 3/2; n = 89, 72.4 %) and poor (grades 1/0; n = 34, 27.6 %) responders. Performance status (p = 0.02), hemoglobin level (p = 0.005), and platelet counts (p = 0.03) were statistically significant pretherapeutic factors for a response to nCRT. Multivariable analysis subsequently selected the hemoglobin level (odds ratio 1.52; 95 % confidence interval 1.08–2.15; p = 0.02) as the sole independent predictor. Receiver operating characteristic curves showed that the optimal cutoff for pretherapeutic hemoglobin was 13 g/dl for predicting a response. We found that 48.8 and 17.1 % of patients with hemoglobin level ≤13 and >13 g/dl, respectively, were poor responders (p = 0.0002), with 5-year overall survival rates of 40.9 and 58.9 %, respectively (p = 0.048).

Conclusions

Pretherapeutic hemoglobin levels can influence responses and survival after nCRT for ESCC. Thus, hemoglobin levels can serve as a useful marker for tailoring optimal therapies for individual patients with advanced ESCC.     

Specific c-K-ras Gene Mutations as a Tumor-Response Marker in Locally Advanced Rectal Cancer Treated With Preoperative Chemoradiotherapy

Background: Forty percent of patients with colorectal cancer develop mutations in the K-ras gene.Objective: Our objective was to evaluate whether the presence of c-K-ras gene mutations is a useful tumor-response marker in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy.Material and Methods: Thirty seven patients with locally advanced rectal cancer were treated with preoperative chemoradiotherapy. Four to six weeks later, surgery was performed. Specimens were classified according to the UICC-AJC classification. A segment of the tumor was obtained to analyze specific c-K-ras gene mutations. Restriction fragment length polymorphism (RFLP) and single strand confirmation polymorphism (SSCP) techniques were used with a set of probes to detect specific c-K-ras mutations in codons 12, 13, and 61. The 37 patients were divided into Group A (with mutations) and Group B (without mutations).Results: All 37 patients completed the scheduled treatment. Group A consisted of 12 patients, whose tumors were classified and specific c-K-ras mutations were located as follows: eight in codon 12, two in codon 13, and one in codon 61. Group B consisted of 25 patients. The tumors were classified and there were more early-stage tumors in Group A, whereas in Group B there were more advanced-stage tumors (P 5 .05, respectively). The mean follow-up was 36.2 6 18.3 months. All Group A patients survived, whereas 8 of the 25 patients in Group B died due to progressive metastatic disease. Survival in Group A was 100%, whereas in Group B it was 59% (P 5 .03).Conclusions: The presence of specific c-K-ras mutations is an indicator of tumor response in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy and surgery. Therefore, responding patients may be more amenable to less radical surgical procedures based on c-K-ras mutations.     

低位局部进展期直肠癌新辅助放化疗后完全缓解的后续手术治疗效果

目的 探讨低位局部进展期直肠癌新辅助放化疗后完全缓解病例的进一步治疗方案及效果。方法 回顾性分析江苏省中医院肿瘤外科2008年1月至2010年5月期间行新辅助放化疗后初步判断达到病理完全缓解（pCR）的14例低位局部进展期直肠癌患者的临床资料。结果 14例患者中接受手术者10例,术后真正达到pCR者5例;术后2例复发或转移,其中死亡1例,1例带瘤生存,余8例患者均无瘤生存。未行手术的4例患者中,有3例复发或转移,其中2例死亡,1例带瘤生存;余1例无瘤生存。 4例未行手术病例中CEA水平正常者（＜5 μg/L）2例（1例复发或转移）,CEA升高的2例均发生转移;10例手术病例中CEA水平正常者6例（均无瘤生存,4例真正达到pCR）,升高者4例（1例真正达到pCR,2例复发或转移）。结论 接受新辅助放化疗后初步判断达到pCR的病例,尤其是CEA值高于正常者,应接受规范的全直肠系膜切除（TME）手术以达到根治的目的。     

Neoadjuvant Chemoradiation Versus Hyperfractionated Accelerated Radiotherapy in Locally Advanced Rectal Cancer

Background Neoadjuvant therapy is increasingly used in resectable locally advanced rectal cancer. The exact role of the addition of chemotherapy is not established. We compared neoadjuvant therapy using chemoradiation (CRT) or hyperfractionated accelerated radiotherapy (HART). Methods Clinical, pathological, and survival data were obtained from patients with resectable stage II or III rectal cancer within 7 cm from the anal verge. A group of 50 patients was treated with a preoperative dose of 41.6 Gy of radiotherapy (RT) in two daily fractions of 1.6 Gy over 13 days immediately followed by surgery (HART). A second group of 96 patients received 45 Gy of conventionally fractionated RT in 25 daily fractions of 1.8 Gy combined with 5-fluorouracil–based chemotherapy followed by surgery within 4 to 6 weeks (CRT). Both groups were compared in terms of morbidity, pathological downstaging, local recurrence, and survival. Results Both groups were comparable in terms of preoperative clinicopathological variables. The mean distance from the anal verge was 5.8 cm (HART) versus 4.9 cm (CRT). Sphincter preservation was possible in 74% (HART) versus 83.5% (CRT) of patients (P = .013). The clinical anastomotic leak rate was 2% (HART) versus 2.2% (CRT). Pathological complete response was observed in 4% (HART) versus 18% (CRT) of the resected specimens (P = .002). A pelvic recurrence developed in 6% (HART) versus 4.4% (CRT) of patients (P = .98). Overall 5-year survival was 58% (HART) versus 66% (CRT) (P = .19); disease-free 5-year survival was 51% (HART) versus 62% (CRT) (P = .037). Conclusions Compared with preoperative HART followed by immediate surgery, preoperative CRT followed by a 6-week waiting period enhances pathological response and increases sphincter preservation rate. This could be explained by the addition of chemotherapy or the longer interval between neoadjuvant therapy and surgery. No statistically significant difference was observed in local control or overall survival.     

Impact of Interval between Neoadjuvant Chemoradiotherapy and TME for Locally Advanced Rectal Cancer on Pathologic Response and Oncologic Outcome

Background

The interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer has arbitrarily been set at 6?C8?weeks. However, tumor regression is variable. This study aimed to evaluate whether the interval between neoadjuvant therapy and surgery had an impact on pathologic response and on surgical and oncologic outcome.

Methods

A total of 356 consecutive patients with clinical stage II and III rectal adenocarcinoma were identified. Median age was 63?years, and 65?% were men. All patients received neoadjuvant chemoradiotherapy (45?Gy) with a continuous infusion of 5-fluorouracil. Data on neoadjuvant-surgery interval, type of surgery, pathology, postoperative complications, length of hospital stay, disease recurrence, and survival were reviewed. Patients were divided into two groups according to the interval between neoadjuvant therapy and surgery: ??7?weeks (short interval, n?=?201) and >7?weeks (long interval, n?=?155).

Results

The complete pathologic response rate was 21?%. It was significantly higher after a longer interval (28?%) than after a shorter interval (16?%, p?=?0.006). A longer interval did not affect morbidity or length of hospital stay. After a median follow-up of 4.9?years, the 5-year cancer-specific survival rate was 83?% in the short-interval group versus 91?% in the long-interval group (p?=?0.046), and the free-from-recurrence rate was 73 versus 83?%, respectively (p?=?0.026).

Conclusions

In this retrospective analysis, there seems to be an association between a longer interval after neoadjuvant chemoradiotherapy and complete pathologic response without affecting postoperative morbidity and length of hospital stay, and with no detrimental effect on oncologic outcome.     

Cytoplasmic CD133 Expression is a Reliable Prognostic Indicator of Tumor Regression After Neoadjuvant Concurrent Chemoradiotherapy in Patients with Rectal Cancer

Background

Despite development in therapeutic strategies, such as neoadjuvant concurrent chemoradiotherapy (CCRT), the prognosis of colorectal cancer remains relatively poor. Cancer stem cells (CSC) with several characteristics can lead to therapeutic resistance. CD133 has been identified as a putative CSC marker in colorectal cancer; however, its functional role still needs elucidation. We verified the role of CD133 with emphasis on expression location and correlated the results of CD133 with clinical outcome in colorectal cancer.

Methods

We used immunohistochemistry to investigate the expression of CD133 in samples from 157 patients with colonic adenocarcinoma and from 76 patients with rectal adenocarcinoma who received neoadjuvant CCRT. We also correlated the expression location of CD133 with the clinicopathological parameters and prognosis.

Results

CD133 protein was variably overexpressed in colorectal cancer tissues and was present in three locations: apical and/or endoluminal surfaces, cytoplasm, and lumen. Cytoplasmic CD133 expression level correlated significantly with tumor local recurrence (P?=?0.025) and survival of patients with colorectal cancer (P?=?0.002), and correlated inversely with tumor regression grading (P?=?0.021) after CCRT in patients with rectal cancer.

Conclusions

The expression of CD133 in the cytoplasm is closely associated with local recurrence and patient survival, and may provide a reliable prognostic indicator of tumor regression grading in patients with rectal cancer after CCRT. Cytoplasmic CD133 expression may also help identify the surviving cancer cells in areas with nearly total regression after CCRT.     

Neoadjuvant Concurrent Chemoradiotherapy for Locally Advanced Esophageal Cancer in a Single High-Volume Center

Background

Neoadjuvant chemoradiotherapy (CRT) is now considered the standard of care by many centers in the treatment of both squamous cell carcinoma (SCC) and adenocarcinoma of the esophagus. This study evaluates the effectiveness of a neoadjuvant CRT protocol, as regards pathological complete response (pCR) rate and long-term survival.

Methods

From 2003 to 2011, at Upper G.I. Surgery Division of Verona University, 155 consecutive patients with locally advanced esophageal cancers (90 SCC, 65 adenocarcinoma) were treated with a single protocol of neoadjuvant CRT (docetaxel, cisplatin, and 5-fluorouracil with 50.4 Gy of concurrent radiotherapy). Response to CRT was evaluated through percentage of pathological complete response (pCR or ypT0N0), overall (OS) and disease-related survival (DRS), and pattern of relapse.

Results

One hundred thirty-one patients (84.5 %) underwent surgery. Radical resection (R0) was achieved in 123 patients (79.3 %), and pCR in 65 (41.9 %). Postoperative mortality was 0.7 % (one case). Five-year OS and DRS were respectively 43 and 49 % in the entire cohort, 52 and 59 % in R0 cases, and 72 and 81 % in pCR cases. Survival did not significantly differ between SCC and adenocarcinoma, except for pCR cases. Forty-nine patients suffered from relapse, which was mainly systemic in adenocarcinoma. Only three out of 26 pCR patients with previous adenocarcinoma developed relapse, always systemic.

Conclusions

This study suggests that patients treated with the present protocol achieve good survival and high pCR rate. Further research is necessary to evaluate whether surgery on demand is feasible in selected patients, such as pCR patients with adenocarcinoma.     

Analysis of Early Postoperative Morbidity Among Patients with Rectal Cancer Treated with and without Neoadjuvant Chemoradiotherapy

Background The impact of neoadjuvant treatment and their subsequent early complications in the treatment of rectal cancer has not been adequately assessed. The aim of this prospective study was to evaluate early postoperative morbidity and mortality among patients with rectal cancer treated with adjuvant radiotherapy and chemotherapy followed by surgery, compared with patients treated with surgery alone. We also identified independent risk factors associated with early major complications. Methods Between 1995 and 2004, 273 consecutive patients underwent treatment for rectal cancer. A total of 170 patients (group A) received preoperative radiotherapy with a total of 45–50.4 Gy (180 cGy per day) and 5-fluorouracil-based chemotherapy, followed by surgery; 103 patients (group B) were treated with surgery alone. Dependent variables related to patients, treatment, radiotherapy, and tumor were analyzed. Results Both groups were similar with regard to age, sex, body mass index, American Society of Anesthesiologists (ASA) score, and tumor location but not for ileostomy (27% in group A vs. 6.8% in group B). The number of complications was similar in both groups (43.1% in group A vs. 44.6% in group B). No differences in wound infection (8.2% vs. 7.8%), intra-abdominal abscess (4.7% vs. 4.9%), anastomotic dehiscence (4.2% vs. 3.8%), postoperative hemorrhage (3.5% vs. 3.9%), urinary complications (6.5% vs. 4.9%), paralytic ileus (8.9% vs. 9.7%), or general complications (7.1% vs. 9.6%) were found. The global mortality in the first 30 days after surgery was .7%. An ASA score of III–IV and surgery duration longer than 3 hours were identified as independent prognostic factors for early complications. Conclusions Preoperative chemoradiation in patients with rectal cancer treated with surgery is not associated with a higher incidence of early postoperative complications. The patient’s preoperative clinical condition and lengthy surgery time are prognostic factors for early complications.     

术前放化疗结合全直肠系膜切除在低位进展期直肠癌治疗中的应用

目的 分析术前放化疗结合全直肠系膜切除术(TME)治疗低位进展期直肠癌的疗效.方法 回顾性分析笔者所在医院2009年1月至2011年12月期间行术前放化疗联合TME的31例低位进展期直肠癌患者的临床资料.放疗采用常规分割放疗,总剂量50 Gy/25 f;化疗采用mFOLFOX6或CapeOX方案.临床-病理对照记录疗效,并评价保肛患者的肛门功能.结果 全部患者均接受TME手术治疗,手术并发症发生率为12.9％(4/31),死亡率为3.2％ (1/31).经术前放化疗,肿瘤直径平均缩小21.9％;48.4％ (15/31)的患者出现T分期下降,阳性淋巴结患者比例由83.9％ (26/31)降至38.7％ (12/31),5例(16.1％)患者获得病理学完全缓解,总有效率达74.2％ (23/31);Ⅲ～Ⅳ度不良反应发生率为6.5％ (2/31),保肛患者肛门功能良好率达84.6％ (22/26).结论 从本组有限的病例看,对低位进展期直肠癌采用术前放化疗结合TME手术能够达到部分肿瘤的病理学完全缓解,缩小原发肿瘤,降低局部淋巴结转移率,从而达到降低肿瘤分期、提高手术疗效的目的.     

Comparison of Magnetic Resonance Imaging and Histopathological Response to Chemoradiotherapy in Locally Advanced Rectal Cancer

Background

Magnetic resonance imaging (MRI) methods for chemoradiotherapy (CRT) response assessment of rectal cancer include posttreatment T staging (ymrT), tumor regression grading (mrTRG), volume reduction posttreatment, and modified RECIST measurement. We compared these methods in identifying good versus poor responders with the histopathological standards of T stage (ypT) and tumor regression grading (TRG).

Methods

A total of 86 patients underwent CRT in a prospective phase II trial for MRI-defined locally advanced rectal cancer. Two readers independently assessed MRIs for ymrT, mrTRG, volume change, and RECIST. Parameters for each case were categorized as good or poor response and analyzed against ypT and TRG by univariate logistic regression.

Results

A total of 83 patients had evaluable imaging, and 78 had final pathology (five did not undergo surgery). Of these, 34 patients had good response (ypT0-3a) and 44 had poor response (>ypT3a). Also, 27 patients had favorable pathologic TRG (predominant fibrosis) and 51 had unfavorable TRG (predominant tumor). Good mrTRG and ymr P?=?0.001) associated with favorable pathology odds ratio [OR]?=?16.11 (95?% confidence interval [95?% CI]: 3.36?C77.29) and 17.50 (95?% CI: 5.38?C56.89), respectively. RECIST measurements and volume reduction of >80?% showed an OR of 3.23 (95?% CI: 1.14?C9.17), 4.25 (95?% CI: 0.92?C15.45), respectively, for a good ypT score (P?=?0.028), but there was no association for histopathological TRG.

Conclusion

Favorable and unfavorable histopathology are predicted by both ymrT and mrTRG, and we recommend these parameters for post-treatment assessment of rectal cancers treated with CRT.     

新辅助放化疗联合盆腔脏器切除术治疗45例复发性直肠癌

目的：探讨新辅助放化疗联合盆腔脏器切除术在复发性直肠癌治疗中的价值。方法：对45例复发直肠癌患者采用新辅助放化疗方案治疗常规分割放疗,治疗结束后4～6周进行盆腔脏器切除手术。结果：经新辅助放化疗后,病理完全缓解9例,肿瘤平均缩小38.4%,68.9%的病例T期下降。全组R0切除率为82.2%,手术并发症为20.0%,3年生存率为80.0%,5年生存率为44.4%。结论：新辅助放化疗联合盆腔脏器切除术是治疗复发性直肠癌的有效方法,通过降低肿瘤病期,提高手术切除率,从而提高患者生存率。     

Prognostic Factors in Patients with Locally Advanced Rectal Adenocarcinoma Treated with Preoperative Radiotherapy and Surgery

Preoperative radiation therapy (PRT) prior to potential curative resection for rectal adenocarcinoma is not widely accepted. This report evaluates the prognostic factors affecting local recurrence and 5-year survival. This is a retrospective study of 214 patients with primary rectal adenocarcinoma treated from January 1986 to December 1994. A PRT dosage of 45 Gy in 20 fractions was administered to patients with clinically tethered or fixed tumors, and 4 to 8 weeks later surgery was performed (group I). Patients with clinically mobile tumors were treated by surgery alone (group II). There were 130 men and 84 women. The median age was 58 years (range 19–85 years). There were 111 patients in group I: 7 patients had no microscopic residual tumor, 80 had Dukes' A and B, and 24 had Dukes' C. There were 103 patients in group II: 70 patients were classified as Dukes' A and B and 33 as Dukes' C. The mean follow-up of the entire cohort was 62 months (range 2–132 months). Local recurrence was seen in 17% of patients in group I and 35% in group II (p= 0.002). Distant recurrence in patients with metastatic lymph nodes was seen in 79% of group I and in 34% of group II (p= 0.001). The favorable prognostic factors for local control were the administration of PRT and well differentiated cancer. The favorable prognostic factors for survival were age < 50 years and the absence of lymph node metastasis. The administration of PRT diminishes the risk of local recurrence. The presence of metastatic lymph nodes in the postirradiated specimen is an ominous prognostic factor for survival. Therefore such patients should be considered for adjuvant chemotherapy.     

Surgical Resection After Down-Staging of Locally Advanced Hepatocellular Carcinoma by Localized Concurrent Chemoradiotherapy

Background

This study evaluated the down-staging efficacy and impact on resectability of concurrent chemoradiotherapy (CCRT) followed by hepatic arterial infusion chemotherapy (HAIC) in locally advanced hepatocellular carcinoma, and identified prognostic factors of disease-free survival (DFS) and overall survival (OS) after curative resection.

Methods

DFS and OS were investigated using clinicopathologic variables. Functional residual liver volume (FRLV) was assessed before CCRT and again before surgery in patients with major hepatectomy. Tumor marker response was defined as elevated tumor marker levels at diagnosis but levels below cutoff values before surgery (α-fetoprotein < 20 ng/mL, protein induced by vitamin K absence or antagonist-II < 40 mAU/mL).

Results

Of 243 patients who received CCRT followed by HAIC between 2005 and 2011, 41 (16.9 %) underwent curative resection. Tumor down-staging was demonstrated in 32 (78 %) of the resected patients. FRLV significantly increased from 47.5 to 69.9 % before surgery in patients who underwent major hepatectomy. In addition, the OS of the curative resection group was significantly higher than the OS of the CCRT followed by HAIC alone group (49.6 vs. 9.8 % at 5-year survival; p < 0.001). By multivariate analysis, the poor prognostic factors for DFS after curative resection were tumor marker non-response and the presence of a satellite nodule; however, tumor marker non-response was the only independent poor prognostic factor of OS.

Conclusions

CCRT followed by HAIC increased resectability by down-staging tumors and increasing FRLV. Curative resection may provide good long-term survival in tumor marker responders who undergo CCRT followed by HAIC.     

Relationship Between Pathologic T-Stage and Nodal Metastasis After Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer

Background We investigated the relationship between pathologic T-stage and mesorectal metastases after preoperative chemoradiotherapy (CRT) for clinical stage II to III rectal carcinoma.Methods The records of consecutive patients with clinical stage II to III carcinoma of the mid or low rectum who underwent surgery after CRT were reviewed. Indications for preoperative CRT were cancer up to 11 cm from the anal verge, Eastern Cooperative Oncology Group performance status of 0 to 2, age 18 to 75 years, and clinical tumor-node-metastasis stage II or III.Results The study group consisted of 235 patients (148 men and 87 women; median age, 61 years). The pretreatment tumor-node-metastasis stage was as follows: I, n = 1; II, n = 96; and III, n = 138. Radiotherapy was delivered at a median dose of 50.4 Gy. A pathologic complete response on the rectal wall was found in 24% of patients, and nodal metastases were found in 20% of patients. According to the pT stage, the rate of node positivity was 2% for pT0, 15% for pT1, 17% for pT2, 38% for pT3, and 33% for pT4 cases. At multivariate analysis, the best model for predicting pathologic node involvement included young age, positive pretreatment N status, and pT status. On considering pT stage alone, the odds ratio was in the region of 10 for pT1/2 and >20 for pT3/4 patients.Conclusions In patients with pT0 after preoperative CRT for clinical stage II to III mid or low rectal cancer, the risk of nodal metastases is very low. More conservative surgery (local excision) may be considered in these cases.Presented at the 57th Annual Cancer Symposium of the Society of Surgical Oncology, New York, New York, March 18–21, 2004.     

Tumor Response Ratio Predicts Overall Survival in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Background

Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods.

Methods

Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I–III breast cancer who had NAC and pretreatment imaging at City of Hope (1997–2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0–0.4 (strong partial response, SPR), TRR > 0.4–1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan–Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders.

Results

There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016).

Conclusions

TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.