Pathological High-risk Factors Research Articles

Real-world efficacy of adjuvant therapy for totally resected stage I lung adenocarcinoma patients with pathological high-risk factors: propensity score analysis

BackgroundWe investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors.MethodsStudy participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan–Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance.ResultsA total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative.ConclusionsAdjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings.

Abstract 5189: The potential of minimal residual disease (MRD) in guiding adjuvant therapy (AT) decisions in non-small cell lung cancer (NSCLC)

Abstract Background: Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) detection has become a strong prognostic stratification factor in post-operation non-small cell lung cancer (NSCLC). Here we sought to investigate the guiding potential of MRD in informing adjuvant therapy (AT) decisions. Methods: Patients with stage IA-IIIB NSCLC who had undergone confirmed R0 resection were enrolled. Blood samples were collected prospectively one month after surgery before initiation of AT (landmark) and longitudinally every 3-6 months since surgery. Postoperative AT was conducted according to the guideline recommendations and regular radiographical examinations were recommended for relapse surveillance. MRD detection was conducted via the MinerVa platform (Genecast Biotechnology Co., Ltd) using a tumor-informed strategy based on a fixed next-generation sequencing (NGS) panel spanning 769 cancer-related genes. Results: 168 patients were included in this study, with 11 (6.5%) experiencing confirmed relapse. Positive MRD was detected in 10.2% (16/157) of patients at landmark and was associated with a significantly higher risk of shorter disease-free survival (DFS)(HR: 26.2[6.7-102.7], P<0.001), irrespective of disease stage or gene alteration. Dynamic changes in ctDNA status further stratified patients into three subgroups with different prognosis. Consistent negative MRD detected at the landmark and all longitudinal timepoints represented the group with the best prognosis, while positive MRD detected at either the landmark or one subsequent timepoint showed a worse prognosis (Neg-Pos vs. Neg-Neg, HR: 37[3.2-438], P=0.004; Pos-Neg vs. Neg-Neg, HR: 14[1.2-172], P=0.035). The group with the worst prognosis occurred with consistent positive MRD (Pos-Pos vs. Neg-Neg, HR: 50[5.3-473], P<0.001). For patients with negative landmark MRD, there was no significant difference between the DFS of patients who received AT and those who didn’t(P=0.241), and the result was replicated in a highly controversial subgroup: stage I patients with high-risk factors (P=0.130). Besides, whether chemotherapy was applied before targeted therapy in the EGFR-mutant subgroup showed no influence on DFS provided that landmark MRD was negative (P=0.197). In multivariate analysis considering pathological high-risk factors, poor differentiation was identified as an independent risk factor for landmark MRD positivity (HR: 10.6[1.96-168.01], P=0.030). Conclusions: MRD is a strong and steady prognostic factor in post-operative NSCLC. AT may be waved for stage I patients with high-risk factors given that they had negative landmark MRD, same as the adjuvant chemotherapy before targeted therapy for patients with sensitive EGFR mutation. More attention should be paid to poorly differentiated tumors, indicative of a high-risk subgroup with potential residual diseases. Citation Format: Siyu Lei, Haiyan Xu, Yaning Yang, Linyan Tian, Ting Ma, Yan Wang. The potential of minimal residual disease (MRD) in guiding adjuvant therapy (AT) decisions in non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5189.

Correlating somatic copy number alteration in aqueous humour cfDNA with chemotherapy history, eye salvage and pathological features in retinoblastoma

BackgroundThis study determined to probe the potential association between somatic copy number alteration (SCNA) in retinoblastoma (RB) aqueous humour (AH) and pathological high-risk factors, clinical features and previous chemotherapy history.MethodsSingle-centre...

Retrospective analysis of clinical features and fertility outcomes with fertility-sparing treatment of placental site trophoblastic tumor

ObjectiveTo analyze the methods, feasibility, efficiency, and fertility outcomes of fertility-sparing treatment for patients with placental site trophoblastic tumor (PSTT). MethodsClinical data of patients diagnosed with PSTT between April 1998 and April 2020 from Peking Union Medical College Hospital (PUMCH) were retrospectively collected. The clinical features, treatment, and outcomes of patients received fertility-sparing treatment were analyzed and compared with patients suffered hysterectomy. ResultsIn total, 126 patients were included in the study and 29 of them received fertility-sparing treatment. Besides significantly younger age and lower proportion of antecedent term delivery were seen in fertility-sparing group than hysterectomy group, no significant differences were observed in stage, serum β-hCG level, or interval from antecedent pregnancy between the two groups. Conservative surgery was selected individualized and none of them suffered salvage hysterectomy. Patients with clinical or pathological high-risk factors received adjuvant chemotherapy, yet the fertility-sparing treatment did not significantly lengthen chemotherapy duration. All patients in fertility-sparing group achieved complete remission without relapse after 36 to 176 months of follow-up and had sixteen healthy term delivery more than one year after the treatment. ConclusionsFertility-sparing treatment for PSTT can be considered for young patients with localized uterine lesions who strongly desire to preserve their fertility potential. With individualized conservative surgery and selected adjuvant chemotherapy, fertility-sparing treatment will not influence the risk of relapse or overall survival and patients will achieve favorable pregnancy and live birth outcomes.

A Review on Pathological High-risk Factors and Postoperative Adjuvant Chemotherapy in Stage IA Lung Adenocarcinoma

早期非小细胞肺癌患者的生存率有待提高。含实体或微乳头成分、伴脉管侵犯或伴气道播散的浸润性腺癌患者属于复发风险高危人群，需要探索包括根治性手术切除在内的系统治疗方案。而现有指南不推荐IA期患者行术后辅助化疗。本文将综述上述病理高危因素在IA期肺腺癌患者中的研究进展以及辅助化疗在IA期复发风险高危人群中的作用。

Current Methods and Caveats to Risk Factor Assessment in Cutaneous Squamous Cell Carcinoma (cSCC): A Narrative Review.

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer, and the number of deaths due to cSCC is estimated to be greater than the number attributed to melanoma. While the majority of cSCC tumors are resectable with clear margins by standard excision practices, some lesions exhibit high-risk factors for which there is evidence of their association with recurrence, metastasis, and disease-specific death. The most commonly used staging systems and guidelines in the USA for cSCC are based on these clinical and pathologic high-risk factors; however, these are limited in their ability to predict adverse events, thus posing a challenge for implementing risk-directed patient management. Since the development of local recurrence and/or metastasis has a profound impact on the survival of patients with cSCC, accurate identification of patients at high risk for poor outcomes is critical, potentially allowing for early and appropriate adjuvant therapy. This review summarizes the current cSCC literature with a focus on how differing clinical assessments within each of the five selected risk factors (perineural invasion, differentiation, depth of invasion, size, and location) can influence the evaluation of patient outcomes, along with summarizing the utility of staging and guidelines, and highlighting the potential for molecular tools to improve upon cSCC risk assessment.

Weekly Cisplatin vs. Triweekly Docetaxel Plus Cisplatin With Concurrent Chemoradiation in Post-Operative Treatment for Cervical Cancer With High-Risk Pathological Factors: A Randomized Controlled Phase III Trial From a Single Institution

After radical surgery, patients with high-risk factors were recommended adjuvant concurrent chemoradiation (CCRT). Cisplatin and cisplatin-based combination chemotherapy were the most common concurrent chemotherapy in previous studies. However, there are still few randomized controlled studies comparing which is better for survival. We conduct this prospective study to compare triweekly combination chemotherapy with weekly cisplatin chemoradiation in adjuvant radiation for cervical cancer patients with high-risk factors after radical surgery.Patients aged 18-70 years early-stage cervical cancer with high-risk pathological factors (adenocarcinoma/adenosquamous carcinoma, parametrial invasion, positive surgical margins, and lymph node metastasis) after radical hysterectomy were included and randomized 1:2 to the DDP group and DP group. The DDP group received chemotherapy with weekly cisplatin (40 mg/m2) of 5 cycles concurrent with radiation. The DP group received a triweekly regimen of cisplatin (75 mg/m2) plus docetaxel (75 mg/m2) of 4 cycles and the first cycle was initiated within 1-2weeks after surgery. Radiotherapy was started concurrently at the second cycle of chemotherapy in DP group. The primary end point was the rate of disease-free survival (DFS) at 5 years.A total of 268 patients were included in the analysis (91 in the DDP group, 177 in the DP group). The median follow-up period is 54 months (2-90m), and 2 cases were lost to follow-up. Baseline demographic and disease characteristics were balanced among the treatment groups. In the intention-to-treat population, 5-year DFS showed a better trend in DP group than DDP group, although there was no statistically significant difference (85.9% vs 78.0%; HR 1.64; 95% CI, 0.91-2.95, P = 0.096). There was no difference in 5-year OS, DMFS and LRFS between the groups (87.0%, 87.6% and 97.2% for DP group; 79.1%, 82.4% and 94.5% for DDP group, P = 0.127, 0.249 and 0.253, respectively). Distant metastasis was the major pattern of treatment failure and occurred in 37 patients (23 in DP group and 14 in DDP group). Lymph nodes (15/37), lung (9/37), liver (5/37), and bone (7/37) were the most common sites of metastasis. Forty-two patients died, of which 3 died from other causes (1 for cardiac, 1 for renal, and 1 for a second primary tumor). 142(80.2%) patients in DP group and 84(92.3%) patients in DDP group completed the treatment according to protocol. Toxic reactions are most common in hematology and intestinal tract. The incidence of severe acute hematological was significantly higher in the DP group than in the DDP group (47.6% vs 21.8%, P = 0.000), but there was no significant difference in severe intestinal reactions.Compared with weekly cisplatin, tri-weekly combined cisplatin plus docetaxel showed a tendency to improve survival in cervical cancer with pathological high-risk factors, but the difference was not statistically significant. Clinical trials.gov identifier NCT01999933.

Inter-Correlations Between Various High-Risk Pathological Factors in Resected Buccal Mucosal Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> While exploring histopathological high-risk factors for squamous cell oral cancer most studies have included oral tongue as major subsite in their patient population. Buccal mucosal squamous cell carcinoma (BMSCC) being rare in developed countries is a less studied site in this regard. Hence most of the knowledge we have about high-risk factors of BMSCC is extrapolated from oral tongue carcinoma. The objective of this study was to explore inter-correlations between various pathological high-risk factors found in resected specimen of BMSCC. <h3>Materials/Methods</h3> It was a retrospective analysis in which we reviewed the final histopathology of surgical specimen of 150 patients with BMSCC who had undergone upfront surgical resection followed by adjuvant therapy. Various high-risk factors studied were pT Stage, pN Stage, depth of invasion (DOI), grade, perineural invasion (PNI), lymphovascular invasion (LVI), tumor thickness (TT), worst pattern of invasion (WPOI), and extranodal extension (ENE). Inter-correlations were performed between various pathological factors using Spearman's correlation test. <h3>Results</h3> Inter-correlation between various factors were found and shown in Table. <h3>Conclusion</h3> pT stage showed significant positive correlation with pN stage, TT, DOI, PNI, nodal deposit size and with ENE. pN stage showed significant positive correlation with pT stage, PNI, LVI, WPOI and ENE. PNI showed significant positive correlation with pT stage, pN stage, nodal deposit size, ENE, LVI, DOI, TT, WPOI. LVI showed significant positive correlation with PNI, WPOI, pN stage, nodal deposit size and ENE. DOI showed significant positive correlation with pT stage, PNI, TT. TT showed significant positive correlation with pT stage, PNI and DOI. WPOI showed significant positive correlation with pN stage, frozen section margin, PNI, LVI and ENE. ENE showed significant positive correlation with pT stage, pN stage, PNI, LVI and WPOI. Grade, configuration and margin status of the tumor showed no significant association with any of the histopathologic variable. Many of these correlations are not shown in oral tongue cancer in most studies. Hence, it is appropriate that intercorrelation between these factors in BMSCC should be dealt differently than in oral tongue cancer. BMSCC may have different biology than oral tongue cancer.

Cervical cancer patterns of care in Italy: A radiation oncology survey of MITO and AIRO GYN groups

Large heterogeneity in therapeutic approaches to cervical cancer (CC) patients has been registered worldwide; a national survey exploring practice settings and equipments in CC treatment was distributed to radiation oncologists. Questionnaires were compiled in 90 of 194 Centers (compliance: 46.3 %). Most of respondents reported the presence of multidisciplinary tumor board, and modern equipments/techniques; 55.5 % of centers reported >1 brachytherapy (BT) equipment, thus implying the need to refer their patients outside for the remaining centers. Post-surgery radiotherapy was performed in 96.7 % of early CC (ECC) cases with pathological high risk factors. Exclusive chemoradiation with concomitant platinum schedules was referred to be used by 84.4 % of centers in locally advanced CC. Alternative options were reported with a range between 4.4 and 28.9 %. The present survey reports a broad spectrum of therapeutic options for CC in Italy. Availability and use of modern techniques is quite diffuse, but the distribution of BT resources and skills remains a challenge.

The relationship between ovarian function and ovarian limited dose in radiotherapy postoperation of ovarian transposition in young patients with cervical cancer.

In this study, the relationship between ovarian function and ovarian limited dose in radiotherapy was evaluated in young patients with cervical cancer who underwent ovarian transposition (Fig1B). Moreover, the novel ovarian dose limit for a better preservation of ovarian function in intensity‐modulated radiation therapy (IMRT) was determined. We retrospectively analyzed data from 86 patients with cervical cancer who received radical hysterectomy and ovarian transposition from January 2013 to June 2015. In agreement with the National Comprehensive Cancer Network Guidelines (NCCN) for Cervical Cancer Version 2.2015, 65 patients with pathological high‐risk factors were administered adjuvant radiotherapy—20 of them received three‐dimensional conformal radiotherapy (Observation Group A), 24 patients received IMRT with no limitation on radiation dose to ovaries (Observation Group B), and 21 patients underwent IMRT with limited radiation dose(V10<20%) to ovaries (Observation Group C). Twenty‐one patients without any predetermined high‐risk factors did not received radiation therapy (Control Group D). Patients from all four groups were followed up, and sex hormone levels (E2, P, follicle‐stimulating hormone [FSH], LH) before radiation, postradiation, 3 month, and 6 month after the radiation therapy were measured by electrochemiluminescence immunoassay. Subsequently, changes in sex hormone levels in all four groups of patients at various time points were analyzed. The levels of sexual hormones (E2, P, FSH, LH) before radiation, postradiation, 3 month, and 6 month after the radiation therapy in patients from all three observation groups were significantly lower than those in patients of the control group (P < 0.05). There was no statistically significant difference in the levels of sex hormones in patients of the control group at different time points (P > 0.05). Within each observation group, there was a statistically significant difference in the sex hormone levels in patients before the radiation and after the radiation (P < 0.05); however, when data from all three observation groups were compared, only the difference in the levels of FSH and LH between the patients from Group A and Group C was statistically significant (P < 0.05). The results of receiver‐operating characteristic (ROC) curve analysis suggested that limiting ovarian radiation dose to V7.5 < 26% in IMRT prevents the disruption of ovarian function (area under ROC curve was 0.740, confidence interval [CI] = 0.606–0.874). In young patients with cervical cancer who underwent radical hysterectomy and ovarian transposition without receiving adjuvant radiotherapy, ovarian endocrine function was well preserved. In patients who received any type of postoperative radiotherapy, ovarian function was affected, suggesting that the standard ovarian limited dose used in IMRT disrupted ovarian function. The results of the ROC curve analysis suggested that the new optimal dose limit of V7.5 < 26% should be used in IMRT to preserve ovarian function (P = 0.003).

Pathologic Risk Factors and Oncologic Outcomes in Early-stage Cervical Cancer Patients Treated by Radical Hysterectomy and Pelvic Lymphadenectomy at a Thai University Hospital: A 7 year Retrospective Review.

To evaluate the rate of pathologic high-risk factors, intermediate-risk factors, and treatment outcomes in early-stage cervical cancer patients undergoing radical hysterectomy and pelvic lymphadenectomy (RHPL). Medical records of stage IA-IIA1 cervical cancer patients who underwent RHPL during the 2006 to 2012 time period and patient follow-up data until December 2013 were reviewed. Of 331 patients, 52 women (15.7%) had pathologic high-risk factors and 59 women (17.8%) had intermediate-risk factors without high-risk factors. All studied patients had an initial complete response. At median follow-up time of 40.9 months (range 1-103.3 months) and mean follow-up time of 43.3±25.3 months, 37 women had disease recurrence and 4 women had died of disease. The most common site of recurrence was the pelvis (64.8%). Five- year and 10-year disease free survival rates were 96.1% and 91.5%, respectively. Five-year and 10-year overall survival rates were 100% and 99.4%, respectively. Independent factors related to recurrence were pelvic node metastasis (odds ratio [OR], 2.670; 95%CI, 1.001-7.119), and >1/3 cervical stromal invasion (OR, 3.763; 95%CI, 1.483-9.549). The rates of pathologic high-risk and intermediate-risk factors should be considered and disclosed when counseling patients regarding primary treatment by RHPL. Oncologic outcomes of primary surgical treatment for early-stage cervical carcinoma were found to be excellent.

Phthisis Bulbi: Clinical and Pathologic Findings in Retinoblastoma

Purpose: Phthisis bulbi represents an ocular end-stage disease characterized by shrinkage and disorganization of the eye. We aim at identifying the pathologic changes of phthisis bulbi associated with retinoblastoma. Design: Retrospective observational case series study. Methods: 16 enucleated eyes were enrolled retrospectively between 2007 and 2012. Pathologic gross and microscopic findings were assessed. Results: Cases showed grossly shrunken eyes with a mean volume of 4.3 cc. Sclera was markedly thickened in the majority of cases with mean of 2272.8 μ. Choroid showed an average thickness of 1029 μ. Necrosis, dystrophic calcification, ossification, gliosis, residual viable tumor was identified in many cases. Pathologic high risk factors were seen in three specimens. Conclusions: We conclude that retinoblastoma must be considered in the differential diagnosis of phthisis bulbi in the pediatric patients and active tumor was present in half of the patients.

Prognostic observation of 465 patients with retinoblastoma with optic nerve invasion

To observe the treatment and prognosis of optic nerve invasion in retinoblastoma (RB). The children who had been diagnosed with unilateral RB and had received enucleation from January 2006 to December 2013 in our hospital were recruited. Tumor extension into the optic nerve were disclosed. Optic nerve involvement was classified into four grades according to the degree of invasion. Grade I is superficial invasion of the optic nerve head only, grade II is involvement up to and including the lamina cribrosa, grade III is involvement beyond the lamina cribrosa, and grade IV is involvement up to and including the surgical margin. Grade I and II are called invasion of the optic nerve before the sieve plate. Grade III and IV are called invasion of the optic nerve after the sieve plate. Other high-risk factors included extensive invasions of the choroid, sclera, anterior chamber, iris, and ciliary body. They were divided into two groups according to whether the merger of other high histopathologic risk factors. Treatment was delivered accordingly, and the prognosis of different degrees of optic nerve invasion was observed. The subjects were followed up for 6 months to 7 years (average: 43 months). There were 465 subjects in this study, including 279 boys and 186 girls. The right eye was affected in 260 patients and the left eye in 205 patients. The average time from onset of symptoms to visit was 2.7 months (range 1 day-24 months). Twenty-five patients died, resulting in an overall survival rate of 94.6%. The mortality rate of patients with optic nerve involvement with grade I was 0.4%, grade II was 1.0%, grade III was 8.7% was and grade IV was 60.9%. Of the 338 with invasion of the optic nerve before the sieve plate, two died of recurrence, with a survival rates of 99.4% (336/338). Of the 127 patients who had invasion of the optic nerve after the sieve plate, twenty-three died of recurrence, with a survival rate of 81.9% (104/127) , the difference was statistically significant (χ² = 52.299, P = 0.000). A total of 379 patients did not have any other merged pathology high-risk factors, 8 died, the mortality rate was 2.1%. Of the 86 patients who had complicated with other high-risk factors, 17 died, the mortality rate was 19.8%, the difference was statistically significant (χ² = 42.955, P = 0.000). Of the 338 patients, 304 had invasion of the optic nerve before the sieve plate had not merged other pathology high-risk factors, none died, of the 34 patients who had complicated with other pathology high-risk factors, 2 had died, the mortality rate was 5.9%, the difference was statistically significant (P = 0.010). Of the 127 patients with invasion of the optic nerve after the sieve plate, 76 had not complicated with other pathological high-risk factors, 9 of whom had died, the mortality rate was 11.8%, 51 had complicated with other pathological high-risk factors, 14 of whom had died, the mortality rate was 27.5%, outcomes did significantly differ between the two subgroups (χ² = 5.014, P = 0.025). Cox multivariate analysis showed that invasion of the retrolaminar optic nerve, surgical margin of the optic nerve and sclera were influential factors of colorectal cancer. Patients with optic nerve invasion have an excellent outcome with current therapy. But for those whose resection margin was invaded, which has a high incidence of recurrence, chemotherapy is recommended for patients with postlaminar optic nerve involvement.

Phase III randomised controlled trial of neoadjuvant chemotherapy plus radical surgery vs radical surgery alone for stages IB2, IIA2, and IIB cervical cancer: a Japan Clinical Oncology Group trial (JCOG 0102)

Background:A phase III trial was conducted to determine whether neoadjuvant chemotherapy (NACT) before radical surgery (RS) improves overall survival.Methods:Patients with stage IB2, IIA2, or IIB squamous cell carcinoma of the uterine cervix were randomly assigned to receive either BOMP (bleomycin 7 mg days 1–5, vincristine 0.7 mg m−2 day 5, mitomycin 7 mg m−2 day 5, cisplatin 14 mg m−2 days 1–5, every 3 weeks for 2 to 4 cycles) plus RS (NACT group) or RS alone (RS group). Patients with pathological high-risk factors received postoperative radiotherapy (RT). The primary end point was overall survival.Results:A total of 134 patients were randomly assigned to treatment. This study was prematurely terminated at the first planned interim analysis because overall survival in the NACT group was inferior to that in the RS group. Patients who received postoperative RT were significantly lower in the NACT group (58%) than in the RS group (80% P=0.015). The 5-year overall survival was 70.0% in the NACT group and 74.4% in the RS group (P=0.85).Conclusion:Neoadjuvant chemotherapy with BOMP regimen before RS did not improve overall survival, but reduced the number of patients who received postoperative RT.

Outcome of stage IB2–IIB patients with bulky uterine cervical cancer who underwent neoadjuvant chemotherapy followed by radical hysterectomy

We performed a retrospective study to clarify the outcome of stage IB2-IIB patients with bulky cervical cancer who underwent neoadjuvant chemotherapy (NAC) followed by radical hysterectomy and adjuvant treatment. Sixty-five patients with bulky stage IB2-IIB cervical cancer, treated at Tottori University Hospital between 2001 and 2011, were examined retrospectively. The indication for adjuvant treatment was limited to the following pathological high-risk factors: pelvic lymph node (PLN) involvement, parametrial infiltration (PI), and a compromised surgical margin. Fifty-one patients had squamous cell carcinoma (SCC) and 14 non-SCC. Three patients were ineligible for radical hysterectomy after NAC, and underwent concurrent chemoradiotherapy. In 62 patients who underwent radical hysterectomy, 13 had only PLN involvement and 6 only PI, and 10 had both PLN involvement and PI. In 33 patients who had no adjuvant treatment, 6 recurred, and only one underwent salvage chemotherapy. In 29 patients who underwent adjuvant treatment, 15 recurred and 11 died. Multivariate Cox proportional analysis revealed that PLN involvement was an independent prognostic factor. Even if the indication for adjuvant treatment is limited to only high-risk patients, about 70 % of stage IB2-IIB patients with bulky cervical cancer could be cured by NAC followed by radical hysterectomy. Additionally, about 40 % of those patients could be cured without adjuvant treatment. In contrast, the strategy for patients with PLN involvement, who account for about 35 % of stage IB2-IIB bulky cervical cancer after NAC, should be carefully reconsidered based on quality of life and cost-effectiveness.

Neoadjuvant therapy for adenocarcinomas of the duodenum and ampulla of Vater.

279 Background: Adenocarcinomas of the ampulla of Vater and duodenum are both rare periampullary tumors with limited data regarding the use of neoadjuvant therapy. We sought to better define the role of neoadjuvant therapy as compared to adjuvant therapy in patients with high-risk disease. Methods: Retrospective review of the M. D. Anderson Cancer Center (MDACC) tumor registry from 5/1990 to 1/2009 identified 66 cases of ampullary (26 neoadjuvant, 40 adjuvant) and 41 cases of duodenal adenocarcinoma (18 neoadjuvant, 23 adjuvant). Only patients who received adjuvant or neoadjuvant therapy and underwent surgical resection at MDACC where included. High-risk factors were defined as T3 or T4, poor differentiation, or lymph node involvement. Relapse-free survival (RFS) and overall survival (OS) were calculated from the start of surgical resection. Results: Median age was 61 yrs (range 30-82) and 39% were female. Neoadjuvant (n=44) and adjuvant therapy (n=63) consisted of 5-FU chemoradiation in 93% and 65%, systemic 5-FU based chemotherapy only in 5% and 24%, and gemcitabine or irinotecan based therapy in 2% and 11%, respectively. Pathological high-risk factors were seen in 77% and 95% of neoadjuvant and adjuvant patients, respectively. Indications for neoadjuvant therapy were high risk disease (70%), poor surgical candidate (16%), and concern for possible metastatic disease (14%). In the neoadjuvant group T and N downstaging were observed in 25% and 32% of patients, respectively; 3 patients (7%) had a pathological complete response. Neoadjuvant as compared to adjuvant therapy had similar 5-year OS (66% vs. 59%, p =0.8) and 5-year RFS (54% vs. 59%, p=0.4). Variables significant (p &lt;0.05) in the multivariate analysis for OS were age &gt;60 yrs, lymph node involvement, and margin positivity; and for RFS were lymph node involvement and margin positivity. Neither tumor type (duodenal vs. ampullary; OS HR: 1.6, p =0.2; RFS HR: 0.9, p=0.8) nor treatment type (neoadjuvant vs. adjuvant; OS HR: 1.2, p =0.6; RFS HR: 1.1, p=0.7) were significant for OS or RFS in the multivariate model. Conclusions: Neoadjuvant therapy appears to be a viable approach for high-risk duodenal and ampullary adenocarcinomas. Further investigation of this treatment approach is needed. [Table: see text]

Postprostatectomy Radiation Therapy for Prostate Cancer

Radical prostatectomy is the most common initial treatment for prostate cancer. Patients with high-risk pathologic features, such as a positive margin or seminal vesicle involvement, have a 40% to 50% risk of developing biochemical failure at some point in the future. Radiotherapy to the prostate bed has been used both adjuvantly and for salvage. There continues to be an active debate regarding when radiation should be administered, although 3 recent randomized trials show a consistent improvement in biochemical failure when adjuvant radiotherapy is administered as compared with radical prostatectomy alone. Because the morbidity of postoperative radiotherapy is relatively low, when pathologic high risk factors are present adjuvant radiotherapy should be considered. The role of androgen deprivation postprostatectomy is less well defined.

Pattern of lymph node metastasis and the optimal extent of pelvic lymphadenectomy in FIGO stage IB cervical cancer

To evaluate the distribution pattern of lymph node metastasis and to determine the optimal extent of pelvic lymphadenectomy (LA) in FIGO stage IB cervical cancer. The medical records of 187 patients with FIGO stage IB cervical cancer from March 1996 to December 2002 were reviewed retrospectively. The distribution pattern and risk factors of lymph node metastases were analyzed in 31 patients with lymph node metastases confirmed surgically. One hundred patients, who underwent type III hysterectomy with pelvic LA but did not receive any adjuvant treatment, were analyzed to evaluate whether the extent of LA affected the prognosis of FIGO stage IB cervical cancer. Type I LA included the external iliac nodes, hypogastric nodes, obturator nodes, and parametrial nodes. Type II LA included the pelvic nodes described in type I LA, the common iliac nodes, gluteal nodes, deep inguinal nodes and sometimes the presacral nodes. Solitary lymph node metastasis confined to one node group was seen in the obturator, external iliac or hypogastric lymph nodes. All patients with lymph node metastases at multiple sites had metastasis in at least one of these lymph-node groups. There was no significant difference in disease-free survival and overall survival in patients without pathologic high-risk factors according to the type of pelvic LA. The extent of LA should be adjusted to reduce complications and not to affect adversely the prognosis of FIGO stage IB cervical cancer patients without pathologic high-risk factors.

The benefits of comprehensive surgical staging in the management of early-stage epithelial ovarian carcinoma.

The management of understaged patients with apparent clinically early ovarian cancer is difficult. Options include offering chemotherapy based on histopathologic factors or reoperation to obtain the necessary information needed to assign an accurate surgical stage. This study aims to compare these two approaches and to define the role of staging surgery in this common patient population. Retrospective chart reviews were carried out at the Universities of Manitoba and Saskatchewan over the period 1975 to 1999. Demographic data and surgical findings were abstracted and entered into a computerized database for analysis. Patients not having surgical staging procedures were offered platinum-based chemotherapy based on high tumor grades, dense adhesions, and presence of surface excrescences or large necrotic areas. Patients with surgically proven stage I disease were treated with no further therapy regardless of histopathologic factors. Descriptive statistics are used to summarize the data. Logistic and Cox regression models are used to identify significant predicting factors for recurrences and progression-free intervals. One hundred and thirty-eight patients presented with tumor macroscopically confined to the ovary at the time of laparotomy. The median age at presentation is 56.5 (18-90). The histology distribution was serous tumor in 28.3%, mucinous in 26.1%, endometrioid in 23.2%, clear cell in 14.5%, anaplastic in 2.2%, and mixed types in 5.8%. The grade distribution was 47.1% grade 1, 27.5% Grade 2, and 25.4% Grade 3. Sixty-eight percent of the patients had a comprehensive surgical staging procedure initially. Thirty-six percent of these patients were found to have extraovarian metastases and were subsequently treated with adjuvant chemotherapy. Forty-three percent of those not having staging laparotomy were offered chemotherapy based on high risk factors only. At a median follow-up of 58 months. 77% of patients remained disease-free and 23% had recurrent disease. Of 60 patients with surgically proven stage I treated expectantly, 6 (10%) recurred, whereas of 25 unstaged patients treated expectantly due to lack of risk factors 7 (28%) recurred (P = 0.036). In patients treated expectantly, a significant survival advantage was noted in the staged group. Logistic regression showed age (OR 1.032, P = 0.043), high grade (OR 4.16, P = 0.003), and lack of a proper staging surgery (OR 2.62, P = 0.032) to be important factors predicting recurrence. In terms of progression-free interval, only age (OR 1.027, P = 0.048) and tumor grade (OR 3.62, P = 0.05) are significant predictors. Absence of surgical pathologic high-risk factors is inferior to comprehensive staging laparotomy findings in guiding recommendations for subsequent adjuvant therapy. Patients who have not been properly staged stand a significant risk of recurrent disease despite more frequent use of chemotherapy. All clinically early-stage ovarian cancer patients should be considered for comprehensive staging surgery prior to further treatment recommendations.