Clinical Clinical Complete Response Research Articles

Long-term outcomes of multimodal therapy combining definitive chemoradiotherapy and salvage surgery for T4 esophageal squamous cell carcinoma.

Survival outcomes of patients with cT4 esophageal squamous cell carcinoma (ESCC) remain extremely poor. We aimed to investigate long-term outcomes and identify prognostic factors in patients treated by definitive chemoradiotherapy (dCRT) alone or with dCRT plus salvage surgery (SALV) for cT4 ESCC. In total, 73 patients completing dCRT were analyzed. Patients achieving clinical complete response (CR) received follow-up evaluations thereafter. For patients diagnosed with clinical partial response (PR), potentially curative SALV was generally performed. Possible prognostic factors included demographic data, tumor staging, blood chemistry profiles, and esophageal stenosis. The 1- and 3-year overall survival (OS) rates of the 73 patients were 67.1% and 40.8%, respectively. Twenty-one patients (29%) achieved clinical CR with dCRT alone. Among 35 patients (48%) with clinical PR, 31 underwent SALV and 4 opted for non-surgical treatments. In the dCRT-alone group (n = 42), patients with clinical CR-PR (n = 25) showed significantly better 3-year OS than those who responded poorly to dCRT (stable or progressive) (n = 17) (67.5% vs. 0%, P < 0.001). In the SALV group (n = 31), curative SALV (n = 22, 73%) provided significantly better 3-year OS than non-curative SALV (58.7% vs. 0%, P < 0.001). Multivariable analysis revealed stenosis before dCRT (P = 0.02) and pretreatment elevated CRP (P = 0.02) to be independently associated with poor outcomes. The multimodal treatment strategy combining dCRT and SALV is rational for treating cT4 ESCC patients. When curative resection is feasible, SALV can provide good long-term survival outcome for patients who responded to dCRT but did not achieve clinical CR with dCRT alone.

Predictive factors of an axillary pathological complete response of node-positive breast cancer to neoadjuvant chemotherapy.

The present study aimed to identify the predictive factors of an axillary pathological complete response (Ax-pCR) in patients with node-positive breast cancer who underwent neoadjuvant chemotherapy (NAC). The present study included 219 patients who underwent NAC followed by curative surgery, including axillary lymph node dissection (ALND), for 221 breast cancers between January 2010 and April 2018. All patients were clinically and/or pathologically confirmed to be node-positive at the initial diagnosis. The predictive factors of Ax-pCR were analyzed using a chi-square test and multivariate logistic regression models. Ninety-five patients (43%) achieved Ax-pCR after NAC. The odds of achieving Ax-pCR were significantly improved when tumors were high grade (odds ratio [OR] 2.20, 95% confidence interval [CI] 1.00-4.84), estrogen receptor (ER) negative (OR 2.65 95% CI 1.23-5.70), ycN0 on ultrasound (US) imaging (OR 3.89, 95% CI 1.90-7.97), and showed a clinical complete response (CR) at the primary site after NAC (OR 4.22, 95% CI 1.59-11.27). Ax-pCR was more likely to be achieved in patients who were diagnosed with ER-negative and high-grade breast cancer and those with ycN0 and clinical CR at the primary site after NAC than among others. Among these patients, those with initially cN1/N2 might be good candidates for a deescalated treatment strategy after NAC.

Maintenance olaparib after platinum-based chemotherapy in patients (pts) with newly diagnosed advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): Efficacy by surgical and tumor status in the Phase III SOLO1 trial.

5541 Background: In SOLO1 (NCT01844986), maintenance olaparib significantly improved progression-free survival (PFS) vs placebo (HR 0.30; 95% CI 0.23–0.41; Moore et al. N Engl J Med 2018) in pts with newly diagnosed advanced OC and a BRCAm. This analysis evaluates olaparib efficacy by timing of surgery, presence of residual tumor following surgery and response status after completion of chemotherapy in SOLO1. Methods: Pts underwent cytoreductive surgery and were in clinical complete response (CR) or partial response (PR) after platinum-based chemotherapy. Pts were stratified by response and received olaparib tablets 300 mg twice daily or placebo. Investigator-assessed PFS and objective response were assessed using modified RECIST v1.1. Results: 260 pts were randomized to olaparib and 131 to placebo; one pt did not receive placebo. Median follow-up was 41 months in both arms. 63% and 35% of pts underwent upfront and interval surgery, 21% and 76% had residual and no residual macroscopic disease after surgery, and 74% and 26% entered the study in clinical CR and PR (based on electronic case report form [eCRF] data). PFS was significantly improved regardless of the timing of surgery, residual disease status after surgery or response after platinum-based chemotherapy (Table). In pts with baseline radiologic evidence of disease (n=80; eCRF), the objective response rate was 43% for olaparib (CR, 28%) and 23% for placebo (CR, 12%). Conclusions: Maintenance olaparib improved outcomes compared with placebo in pts with newly diagnosed advanced OC and a BRCAm, regardless of surgical or tumor status. Clinical trial information: NCT01844986. [Table: see text]

Impact of Immunohistochemistry-Based Subtypes in Muscle-Invasive Bladder Cancer on Response to Chemoradiation Therapy

A bladder-sparing strategy is a useful option for patients with muscle-invasive bladder cancer (MIBC), in which the response to chemoradiation therapy (CRT) is primarily important in achieving favorable oncologic outcomes. Our objective is to evaluate the impact of immunohistochemistry (IHC)-based subtyping in MIBC on prediction of CRT response. Treatment protocol consisted of induction CRT followed by partial or radical cystectomy as consolidative surgery; 118 eligible patients with nonmetastatic MIBC were retrospectively analyzed. Of these patients, 92 eventually underwent partial or radical cystectomy after CRT. We applied the IHC-based subtyping model developed by Lund University, which classifies patients into urobasal (Uro), genomically unstable (GU), and squamous cell cancer-like (SCCL) subtypes. GU and SCCL cancers are supposed to be highly aggressive and to have worse prognoses than Uro. Correlations of subtypes with CRT response were analyzed clinically in all patients and pathologically in 92 cystectomized patients. The impact of each subtype on cancer-specific mortality (CSM) was also analyzed. Of all patients, 26 (22%), 61 (52%), and 31 (26%) were classified into Uro, GU, and SCCL subtypes, respectively. Clinical complete response (CR) was achieved in 42% of patients overall after CRT, with a significantly higher proportion in GU patients (52%) and SCCL patients (45%) than in Uro patients (15%; P<.001 and P=.01, respectively). On multivariate analysis, the GU/SCCL subtype was a significant predictor of clinical CR, as was absence of hydronephrosis or concomitant carcinoma in situ. Analyses for pathologic CR in the cystectomized patients revealed analogous findings. Five-year CSM of Uro, GU, and SCCL patients was 16%, 23%, and 28% overall, respectively, and 19%, 22%, and 23% in cystectomized patients, respectively, with no significant difference among the subtypes. CR status after CRT was significantly and independently correlated with low CSM in both clinical and pathologic evaluations. GU and SCCL cancers showed significantly more favorable CRT response than did Uro cancers. IHC-based subtyping may improve clinical decisions about the indication of CRT for MIBC patients.

P.4.a.003 - Neural substrates of fear conditioning are modulated by GLRB allelic variation: converging evidence from an independent replication

A bladder-sparing strategy is a useful option for patients with muscle-invasive bladder cancer (MIBC), in which the response to chemoradiation therapy (CRT) is primarily important in achieving favorable oncologic outcomes. Our objective is to evaluate the impact of immunohistochemistry (IHC)-based subtyping in MIBC on prediction of CRT response.Treatment protocol consisted of induction CRT followed by partial or radical cystectomy as consolidative surgery; 118 eligible patients with nonmetastatic MIBC were retrospectively analyzed. Of these patients, 92 eventually underwent partial or radical cystectomy after CRT. We applied the IHC-based subtyping model developed by Lund University, which classifies patients into urobasal (Uro), genomically unstable (GU), and squamous cell cancer-like (SCCL) subtypes. GU and SCCL cancers are supposed to be highly aggressive and to have worse prognoses than Uro. Correlations of subtypes with CRT response were analyzed clinically in all patients and pathologically in 92 cystectomized patients. The impact of each subtype on cancer-specific mortality (CSM) was also analyzed.Of all patients, 26 (22%), 61 (52%), and 31 (26%) were classified into Uro, GU, and SCCL subtypes, respectively. Clinical complete response (CR) was achieved in 42% of patients overall after CRT, with a significantly higher proportion in GU patients (52%) and SCCL patients (45%) than in Uro patients (15%; P < .001 and P = .01, respectively). On multivariate analysis, the GU/SCCL subtype was a significant predictor of clinical CR, as was absence of hydronephrosis or concomitant carcinoma in situ. Analyses for pathologic CR in the cystectomized patients revealed analogous findings. Five-year CSM of Uro, GU, and SCCL patients was 16%, 23%, and 28% overall, respectively, and 19%, 22%, and 23% in cystectomized patients, respectively, with no significant difference among the subtypes. CR status after CRT was significantly and independently correlated with low CSM in both clinical and pathologic evaluations.GU and SCCL cancers showed significantly more favorable CRT response than did Uro cancers. IHC-based subtyping may improve clinical decisions about the indication of CRT for MIBC patients.

The lymphocyte-monocyte ratio predicts tumor response and survival in patients with locally advanced esophageal cancer who received definitive chemoradiotherapy.

BackgroundThe lymphocyte–monocyte ratio (LMR), a simple biomarker that can reflect the antitumor immune response of the host, has been associated with patient prognosis in several solid tumors. The aim of this study was to evaluate whether LMR can predict clinical tumor response and prognosis in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who received definitive chemoradiotherapy (CRT).Patients and methodsA total of 162 advanced ESCC patients treated at our institution between January 2012 and December 2013 were retrospectively recruited for analysis. Patients were treated with a platinum-based bimodal cytotoxic drug chemotherapy and concurrent radiation therapy. The LMR was calculated from blood counts in samples collected prior to treatment initiation. The predictive value of LMR for clinical tumor response and prognosis was examined.ResultsThe LMR before CRT was significantly higher in 48 patients who achieved clinical complete response (CR) compared to that in patients who did not achieve clinical CR (4.89±1.17 vs 3.87±1.29, P<0.001). Compared to their matched counterparts, patients in the high LMR group (LMR >4.02) showed a good clinical tumor response (P<0.05). A significant independent association between a high pretreatment LMR and better outcomes was identified in a multivariate analysis for progression-free survival (PFS; hazard ratio [HR]=2.17; P<0.001) and overall survival (OS; HR=2.02; P=0.002).ConclusionIn ESCC patients, a high LMR before treatment, which indicates a robust host immune system, is associated with both a good clinical tumor response after definitive CRT and favorable prognosis.

Cytogenetic Response Based On Revised IPSS Cytogenetic Risk Stratification and Minimal Residual Disease Monitoringby FISH In MDS Patients Treated By Low-Dose Decitabine

ObjectiveTo observe and analyze the response characteristics based on revised IPSS (IPSS-R) cytogenetic risk stratification in patients with myelodysplastic syndromes (MDS) who received low-dose decitabine treatment. Patients and methodsEighty-seven MDS patients received decitabine treatment (15-20mg/M2/d×5/per course) with a median of 4 courses (range, 1-10). The clinical and cytogenetic response after treatment were observed to evaluate whether the IPSS-R cytogenetic risk stratification could predict treatment response. For those patients with abnormal karyotypes who achieved clinical complete response (CR), percentage of clonal cells in bone marrow (BM) was calculated by G-banding together with fluorescence in situ hybridization (FISH) to determine the minimal residual disease (MRD). In addition, the effect of cytogenetic response on overall survival (OS) was also analyzed. ResultsSixty of 87 patients (69.0%) achieved treatment response including 25 cases (28.7%) with CR. For the 44 patients with abnormal chromosome, 27 cases (61.3%) achieved cytogenetic response including 18 with complete cytogenetic response (cCR). The patients carrying poor or very poor karyotypes presented better clinical and cytogenetic response than those with intermediate or good karyotypes. Among the patients with poor or very poor karyotypes, the ones carrying chromosome 7 aberrance showed better response than the others. Among 18 patients with abnormal karyotypes who achieved clinical CR, 4 cases presented cytogenetic PR or NR through G-banding analysis. FISH analysis revealed an over 5 % of clonal cells in BM in two patients who presented G-banding defined cytogenetic CR. In addition, longer median OS (24 months) were observed for patients who achieved cytogenetic response than those who did not (12 months) (P=0.007) ConclusionIPSS-R cytogenetic risk stratification could be used to predict the clinical and cytogenetic response to decitabine treatment in MDS patients. The predicting effect may be related to the chromosome 7 involvement rather than the number of abnormal karyotypes. FISH together with G-banding analysis should be available in determining MRD in MDS patients after treatment. Disclosures:No relevant conflicts of interest to declare.

Complete Clinical Response After Neoadjuvant Chemoradiotherapy for Squamous Cell Cancer of the Thoracic Oesophagus: Is Surgery Always Necessary?

BackgroundNeoadjuvant chemoradiotherapy (CT-RT) before oesophagectomy is standard management for squamous cell carcinoma (SCC) of the thoracic oesophagus. The aim of this study was to compare the outcome of patients who had clinical complete response (CR) with neoadjuvant CT-RT + oesophagectomy with the survival of patients who had clinical CR and were not operated on. Patients and MethodsSeventy-seven consecutive patients with SCC of the thoracic oesophagus with CR with neoadjuvant CT-RT presenting at the Regional Center of Esophageal Diseases from 1992 to 2008 were included in this retrospective study on a prospectively collected database. Thirty-nine patients underwent oesophagectomy (CT-RT + oesophagectomy), while 38 (CT-RT) were not operated on because they were considered unfit for surgery or refused the operation. Patients’ outcome and survival were compared. ResultsIn the CT-RT + oesophagectomy group, clinical CR was confirmed after histological examination of the surgical specimen in 27/39 (69.2 %) patients. Five-year overall survival rates were 50.0 % in the CT-RT + oesophagectomy group and 57.0 % in the CT-RT group (p = 0.99); 5-year disease-free survival rates were 55.5 % in the CT-RT + oesophagectomy group and 34.6 % in the CT-RT group (p = 0.15). Even after adjusting for propensity score, age, ASA and clinical stage, the treatment regimen did not show a statistically significant effect on overall survival (adjusted p = 0.65) nor on disease-free survival (adjusted p = 0.15). ConclusionIn our group of patients with clinical CR after neoadjuvant CT-RT for SCC of the thoracic oesophagus, waiting for recurrence and then using salvage surgery did not negatively impact their survival compared to patients treated with surgery. More accurate restaging protocols are warranted to improve decision making after CR with neoadjuvant CT-RT.

1036P - Induction Therapy with Cetuximab, Docetaxel, Cisplatin, and Fluorouracil in Patients with Resectable Non Metastatic Stage III or IV Squamous Cell Carcinoma of the Oropharynx. A Gercor Phase II Study

ABSTRACT Background Docetaxel/cisplatin/5-FU (TPF) has been reported to be more active than cisplatin/5-FU in Squamous Cell Carcinoma (SCC) of the head and neck (HN). A clinical Complete Response (CR) rate of 8.5% was achieved after TPF induction therapy (IT) in patients (pts) with unresectable pharyngolaryngeal SCC (Vermorken et al, NEJM 2007). EGFR is overexpressed in up to 90% of HN cancers. Cetuximab (Cet) was active in combination with radiotherapy and with cisplatin. The aim of this multicenter single-arm phase II study was to evaluate Cet with TPF as IT in oropharyngeal SCC. Methods Main inclusion criteria were: previously untreated histologically proven oropharyngeal SCC, non-metastatic stage III or IV disease (UICC 2002), surgically resectable, age 18-75 years, ECOG Performance Status (PS) 0-1. Pts received Cet iv /1-2h (400 mg/m2 loading dose, then weekly 250 mg/m2) followed by docetaxel iv 75mg/m2 /1h and cisplatin iv 75mg/m2 /1h (day 1); and 5-FU iv 750mg/m2/day continuously (days 1-5), every 3 weeks for 3 courses. After completion of IT, the treatment of the primitive tumor was at the investigator's discretion. The primary endpoint was the clinical and radiological CR of primitive tumor at 3 months. Correlative studies investigated several EGFR-related biomarkers and HPV analyses in tumor and blood samples. Results Among 42 pts enrolled from 07/2008 to 11/2011 in 9 centers, 41 pts were treated. The main pts characteristics were: male 81%, mean age 56y, PS0 79%, tonsil area 88%, stage III/IV 76%/24%. The planned 9 infusions were given in 31 (76%) pts. A clinical and radiological CR of the primitive tumor at 3 months was achieved in 9 (22%) pts, and a clinical CR in 17 (41%) pts. The most frequent G3-4 toxicities were: neutropenia (39%), febrile neutropenia (20%), diarrhea (10%), and mucositis (12%). Any grade acnea-like syndrome was observed in 18 (44%) pts. One toxic death occurred secondary to chemo-induced colitis with colonic perforation. Conclusions The combination of cetuximab with TPF is highly active. A systematic therapy with granulocyte colony-stimulating factor is necessary to prevent febrile neutropenia. Disclosure All authors have declared no conflicts of interest.

Prospective Trial of Synchronous Bevacizumab, Erlotinib, and Concurrent Chemoradiation in Locally Advanced Head and Neck Cancer

We assessed the safety and efficacy of synchronous VEGF and epidermal growth factor receptor (EGFR) blockade with concurrent chemoradiation (CRT) in locally advanced head and neck cancer (HNC). Newly diagnosed patients with stage III/IV HNC received a 2-week lead-in of bevacizumab and/or erlotinib, followed by both agents with concurrent cisplatin and twice daily radiotherapy. Safety was assessed using Common Toxicity Criteria version 3.0. The primary efficacy endpoint was clinical complete response (CR) rate after CRT. Twenty-nine patients enrolled on study, with 27 completing therapy. Common grade III toxicities were mucositis (n = 14), dysphagia (n = 8), dehydration (n = 7), osteoradionecrosis (n = 3), and soft tissue necrosis (n = 2). Feeding tube placement was required in 79% but no patient remained dependent at 12-month posttreatment. Clinical CR after CRT was 96% [95% confidence interval (CI), 82%-100%]. Median follow-up was 46 months in survivors, with 3-year locoregional control and distant metastasis-free survival rates of 85% and 93%. Three-year estimated progression-free survival, disease-specific survival, and overall survival rates were 82%, 89%, and 86%, respectively. Dynamic contrast enhanced MRI (DCE-MRI) analysis showed that patients who had failed had lower baseline pretreatment median K(trans) values, with subsequent increases after lead-in therapy and 1 week of CRT. Patients who did not fail had higher median K(trans) values that decreased during therapy. Dual VEGF/EGFR inhibition can be integrated with CRT in locally advanced HNC, with efficacy that compares favorably with historical controls albeit with an increased risk of osteoradionecrosis. Pretreatment and early DCE-MRI may prospectively identify patients at high risk of failure.

Local excision and selective radical resection after neoadjuvant chemoradiation for rectal cancer.

e14107 Background: 20% of rectal cancer patients with a clinical complete response (CR) after neoadjuvant chemoradiation will have a pathologic CR at radical resection (RR). Local excision (LE) of the primary tumor can identify patients who achieved a pathologic CR/may not require RR. The objective of this study was to explore the predictive/therapeutic value of LE and optimal surgical strategy in this patient population. Methods: We developed a decision analysis/Markov model to compare outcomes following selective versus routine RR in rectal cancer patients with a clinical CR after chemoradiation. All patients in the selective RR strategy underwent LE: patients with a pathologic CR were observed/those with residual disease underwent subsequent RR. Sensitivity/specificity of LE and morbidity/mortality/recurrence/salvage/survival estimates were obtained from the medical literature. Outcomes were quality-adjusted using health state preferences. Results: Quality-adjusted life years (QALYs) after selective RR were 6.22 compared to 6.03 after routine RR (69 additional healthy days gained). Patients with a “true” pathologic CR (at the primary tumor site/mesorectum) gained the greatest benefit (8.46 versus 7.68 QALYs, respectively). Selective RR was the optimal strategy even after model estimates were varied widely over reported ranges. Routine RR became the preferred strategy only if mortality of local excision and probability of pathologic CR were assumed to be >3% and <1%, respectively. Conclusions: Selective RR (based on findings at LE) maximizes quality-adjusted life expectancy compared to routine RR in rectal cancer patients with a clinical CR after neoadjuvant chemoradiation. Routine RR in this increasingly common clinical situation should be strongly reconsidered.

Final results from randomized phase II trial of preoperative docetaxel (D) and capecitabine (C) given sequentially or concurrently for HER2-negative breast cancers.

1118 Background: Achievement of pathologic complete response (pCR) to preoperative therapy is a predictor of improved disease-free and overall survival. Sequential and concurrent regimens of D and C were evaluated in patients with Her2-negative breast cancers who were candidates for preoperative chemotherapy. Methods: Patients with Stage I (>1.0 cm), II or III, Her-negative breast cancer from Georgia-based oncology network were randomized between Arm A: sequential therapy with D 100 mg/m2 every 3 weeks for 4 cycles followed by C 1000 mg/m2 PO BID on days 1-14 of 3 week cycle for 4 cycles; Arm B: concurrent therapy with with D 50 mg/m2 on day 1 and C 1000 mg/m2 PO BID on days 1-7 of 2 week cycle for 8 cycles. Primary endpoint was pCR rate; secondary endpoints included response rate and toxicity. Results: 51 patients were accrued (4/2007–7/2009), Arm A (n=25) Arm B (n=26) and are evaluable for primary endpoint. Patients were accrued at academic center (45%), county hospital (33%), and community sites (22%). Median age was 50.3 years. Median tumor size was 6.1 cm. 35 of 51 (68.6%) were clinically node-positive at study entry. 57% of patients were African American, 35% Caucasian, and 8% other. 30 of 51 (58.8%) of patients had ER and/or PR-positive tumors; 21 of 51 (41.2%) had ER/PR-negative tumors (triple negative). Treatment was well-tolerated with expected grade 3-4 toxicities: neutropenia 15.7%; hand-foot syndrome 5.9%; neuropathy 3.9%. On Arm A, clinical complete response (CR) rate was 32%. Partial response (PR) rate was 28%. Stable disease (SD) rate was 12 %. Progressive disease (PD) rate was 28%. On Arm B, clinical CR rate was 46.2%. PR rate was 42.3%. SD rate was 3.8%. PD rate was 7.7%. pCR rate was 8% for Arm A and 11.5% for Arm B. Among triple negative breast cancer subjects, pCR rate was 19%. Conclusions: This is the first clinical trial to accrue patients through a Georgia-based oncology trial network and more than half of enrolled patients were African American. The final results from this phase II trial of D and C show that both regimens were well-tolerated and had modest clinical activity, with greater activity in the concurrent therapy arm and among triple negative patients.

Prognostic significance of baseline positron emission tomography and importance of clinical complete response in patients with esophageal or gastroesophageal junction cancer treated with definitive chemoradiotherapy

Metabolic imaging is of interest in esophageal cancer; however, the usefulness of initial standardized uptake value (SUV) in positron emission tomography (PET) is unknown in patients with esophageal or gastroesophageal carcinoma treated with definitive chemoradiotherapy. The authors hypothesized that initial SUV would correlate with patient outcome. The authors retrospectively analyzed esophageal or gastroesophageal carcinoma patients who had baseline PET and endoscopic ultrasonography in addition to other routine staging. All patients received definitive chemoradiotherapy. Multiple statistical methods were used. The authors analyzed 209 consecutive esophageal or gastroesophageal carcinoma patients treated with definitive chemoradiation for outcome; of these, 180 had baseline PET for additional analyses. The median overall survival (OS) for all patients was 20.7 months (95% confidence interval, 18.8-26.3). Patients with clinical complete response (CR) lived longer than those with less than clinical CR (P < .0001). The median initial SUV was 12.7 (range, 0-51). Higher initial SUV was associated with longer tumors (P = .0001), higher T-stage status (P < .0001), positive N-stage status (P = .0001), higher overall stage (P < .0001), lack of clinical CR (P = .0002), and squamous cell histology (P < .0001). In the univariate analysis, initial SUV was associated with OS (Cox model, P = .016; log-rank test, P = .002). In the multivariate analysis, initial SUV dichotomized by the median value (P = .024) and tumor grade (P = .016) proved to be independent OS prognosticators. Median initial SUV for clinical CR patients was 10.2, compared with 15.3 for less than clinical CR patients (P = .0058). The data indicate that a higher initial SUV is associated with poorer OS in patients with esophageal or gastroesophageal carcinoma receiving definitive chemoradiation. Upon validation, baseline PET may become a useful stratification factor in randomized trials and for individualizing therapy.

Hypopigmented mycosis fungoides in children: a clinicopathological study of 6 cases

To explore the clinical and histopathological manifestations, therapy and prognosis of hypopigmented mycosis fungoides (HMF) in children. Six pediatric cases of HMF from February 2008 to October 2009 were reviewed and analyzed at our hospital. There were 5 males and 1 female with a average age of 11 years old (range: 9-14). The lesions appeared poorly-demarcated hypopigmented macula and patches disseminated over the trunk and extremities, scales and infiltrated papules over the hypopigmented lesions or invasive erythemas arose and enlarged gradually. Histologically, there was an epidermal infiltration of atypical lymphocytes. The immunohistochemical staining revealed a pattern of T lymphoma and a predominance of CD8+ T cell. All patients were of T2N0M0/IB except for one at the stage of T1N0M0/IA. Two patients received narrow band ultraviolet B (NB-UVB), one NB-UVB plus alpha interferon, another NB-UVB plus alpha interferon and topical steroid, one Chinese traditional herbal regimen while the last one none. And NB-UVB alone or plus alpha interferon achieved a clinical complete response (CR). The herbal regimen failed to cure the lesions but achieved no response. The non-treated patient progressed gradually. The average follow-up was 16 months (range: 9-28). The progression-free rate was 83.3% and the overall survival rate 100%. Visceral and lymph note involvements are rare in HMF of children. The prognosis of early-stage treatment is satisfactory. NB-UVB alone or plus alpha interferon achieves a clinical CR in most early-stage patients.

Radiotherapy in treatment of carcinoma of the parotid gland, an approach for the medically or technically inoperable patient

Initial surgical resection is considered the standard of care for patients diagnosed with tumours involving the salivary glands. We reviewed our institutional outcomes of patients treated with initial radiation therapy (RT) for diagnosed carcinoma of the parotid gland. This review examined seventeen patients that received RT as initial therapy for tumours involving the parotid gland. Fifteen patients had primary salivary gland cancer, and two patients had metastatic carcinoma to the parotid gland. Sixteen patients (94.1%) following surgical evaluation had operative risk of facial nerve impairment or sacrifice with initial surgery, four (23.5%) had clinical objective evidence of nerve involvement at evaluation, five (29.4%) were poor surgical candidates and three (17.6%) refused initial surgery. Primary tumour stages ranged T2-T4b, and disease stages ranged II-IVb. RT median dose was 70 Gy, and median follow-up was 12 months. Eleven patients (64.7%) achieved a clinical complete response (CR) to therapy. Of these CR patients eight (72.7%) received definitive RT and three (27.3%) underwent surgery following RT. Two surgical patients avoided facial nerve impairment while one required nerve sacrifice. The other six patients (35.3%) achieved an unfavourable response to RT and had unresectable or metastatic disease at follow-up. No long-term complications were reported. Initial radiation therapy for tumours involving the parotid gland is effective to achieve clinical CR, eliminate surgical resection for many patients, and decrease risk of facial nerve impairment or sacrifice for those patients requiring surgery following RT.

Diffusion-Weighted MRI in Predicting the Efficacy of Neoadjuvant Chemotherapy of Breast Cancer.

Abstract Objective: To approach the apparent diffusion coefficient(ADC) obtained on diffusion weighted imaging (DWI) in predicting the response of breast cancer to neoadjuvant chemotherapy.Methods: 53 locally advanced breast cancer patients participated in this prospective study on neoadjuvant chemotherapy. All patients were treated with weekly neoadjuvant paclitaxel plus carboplatin for 4 cycles. DWI and ADC value were examined before chemotherapy(the first time point), after the first and the forth cycle of chemotherapy(the second and the third time point). Patients were categorized as high responders if their ADC at the second time point were higher by 2 times the standard deviation than the mean pre-chemotherapy ADC, and otherwise the patients were considered as low responders. Logistic regression was conducted to examine the independent factors predictive of clinical complete response(CR) and pathologic complete response(pCR).Results: CR was documented in 13 patients (24.5%); partial response in 36 patients (67.9%); stable disease in 4 patients (7.5%) and no patient had progressive disease. 11 patients(20.8%) have achieved pCR. There was a strong positive correlation between the percentage changes in ADC value at the third time points and the degree of the tumor reduction. A significant increase in ADC value was observed at the second time point compared with the first time point (1.104±0.117×10-3mm2/s, 1.220±0.158×10-3mm2/s, P&amp;lt;0.001), while the decrease of the longest diameter of the tumors measured by physical examination, ultrasound or MRI or the tumor volumn measured by MRI were not (P&amp;gt;0.05). Logistic regression revealed that percentage changes of ADC value at the second time point were significantly associated with CR(P=0.022, hazard ratio[HR] =1.08, 95% confidence interval[CI]: 1.01∼1.16) and pCR(P=0.022, HR =1.11, 95%CI: 1.02∼1.21). The AUC value of the receiver operating characteristic curve were 0.721(95%CI: 0.512∼0.931, P=0.017) and 0.775(95%CI: 0.598∼0.952, P=0.005) in the two diagnostic tests for CR and pCR, and the sensitivity and specificity were 76.9%, 63.6% and 77.5%, 90.5%, respectively. According to categorizing system described above, 10 patients(18.9%) were considered as high responders and 43 patients(81.1%) low responders. 7 patients(70%) of the high responders have achieved clinical CR and pCR while for the low responders there were only 6 patients(14.0%) and 4 patients (9.3%) proven to have CR and pCR. The difference have both reached statistical significance(P=0.001, P&amp;lt;0.001). Logistic regression confirmed that the categorizing system was independently predictive of CR(P=0.006, HR=42.26, 95%CI: 2.86∼624.08) and pCR(P=0.013, HR=25.19, 95%CI: 2.00∼318.91). Taking this categorizing system as a dignostic test, the sensitivity and specificity were 53.8% and 92.5% for CR and 63.6% and 92.9% for pCR, respectively.Conclusions: The change of ADC value obtained on DWI after the first cycle of neoadjuvant chemotherapy occured prior to the morphologic changes of the tumor and at this time ADC value could to some extent predict the efficacy of neoadjuvant chemotherapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4025.

Rituximab plus Short-Duration Chemotherapy Followed by Yttrium-90 Ibritumomab Tiuxetan as First-Line Treatment for Patients with Follicular Non-Hodgkin Lymphoma: A Phase II Trial of the Sarah Cannon Oncology Research Consortium

PurposeTo evaluate the efficacy and safety of treatment with Yttrium-90 (90Y) ibritumomab tiuxetan following completion of short-course rituximab/chemotherapy in patients with previously untreated follicular non-Hodgkin lymphoma. Patients and MethodsForty-one patients with previously untreated follicular lymphoma received rituximab for 4 consecutive weeks, followed by 3 cycles of rituximab combined with either CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone; 88%) or CVP (cyclophosphamide/ vincristine/prednisone; 12%). To complete treatment, all patients received 90Y ibritumomab tiuxetan 4-6 weeks after the final dose of chemotherapy. The primary efficacy endpoint was the clinical complete response (CR) rate after completion of therapy; all patients were followed for progression-free survival (PFS) and overall survival (OS). ResultsAfter completion of shortcourse rituximab/chemotherapy, 95% had objective responses, with a 30% clinical CR rate. The clinical CR rate increased to 72% following 90Y ibritumomab tiuxetan. After a median follow-up of 67 months, the estimated 5-year PFS and OS rates are 64% and 96%, respectively. Reversible grade 3/4 neutropenia and thrombocytopenia occurred in 39% and 36% of the patients, respectively, following 90Y ibritumomab tiuxetan; nonhematologic toxicity was uncommon. Conclusion90Y ibritumomab tiuxetan was well tolerated after short-course rituximab/chemotherapy and resulted in a high CR rate and a long PFS. Definitive demonstration of improved efficacy versus rituximab/chemotherapy alone will require a randomized phase III trial.

A phase II study of docetaxel followed by vinorelbine and doxorubicin in the neoadjuvant treatment of locally advanced breast cancer

e11542 Background: Neoadjuvant treatment has become a standard of care for inoperable breast cancer patients. Docetaxel combination regimens have shown significant activity in this setting. We evaluated a sequential regimen of docetaxel followed by combination vinorelbine-doxorubicin as neoadjuvant treatment for locally advanced breast cancer. Primary objective is the pathological complete response (pCR) rate. Secondary objectives are the clinical response rate, the resectability rate and the safety profile. Methods: This is a prospective, open-label, phase II study. Patients with locally advanced breast cancer (T3+ or T4 M0) and no prior chemotherapy were eligible. All patients received 3 cycles of docetaxel 100 mg/m2 on d1 every 3 weeks. Patients with clinical complete response (CR) had breast cancer surgery. The remaining patients received 3 cycles of vinorelbine-doxorubicin (vinorelbine 25 mg/m2 on d1 and d8 plus doxorubicin 50 mg/m2 on d1) q3w followed by surgery if responding to treatment. Response assessment was by RECIST. Toxicity was evaluated according to NCI-CTC AE, version 3.0. Results: Out of 90 recruited patients, 50 were evaluable at the time of this analysis. Twenty-three patients (46%) had clinical CR after 3 cycles of docetaxel and underwent breast surgery. Of the remaining 27 patients (54%) who received 3 cycles of vinorelbine-doxorubicin, 10 achieved a clinical CR. Conservative surgery was performed in 44 patients (88%), and 4 had a radical mastectomy. A pCR was seen in 19 patients (38%) and a pPR in 29 patients (58%) for a 96% pathological response rate. The most common grade 2 and 3 toxicities, during docetaxel treatment were nausea and vomiting (32%/34%), neutropenia (36%/50%) and alopecia (48%/68% grade 1 and 2). The most common grade 2 and 3 toxicities during vinorelbine-doxorubicin were respectively, neuropathy (41%/52%), nausea and vomiting (63%/74%), constipation (11%/29%) and alopecia (44%/74% grade 1 and 2). Conclusions: Preliminary results show the efficacy of sequential docetaxel followed by vinorelbine-doxorubicin in inoperable breast cancer patients, with a higher rate of conservative surgery and a manageable toxicity profile. Long term follow-up is needed. No significant financial relationships to disclose.

Clinical and Pathologic Evaluation of the Effectiveness of Neoadjuvant Chemoradiation Therapy in Advanced Esophageal Cancer Patients

Chemoradiation therapy (CRT) has the strongest antitumor effect against local tumors of esophageal cancer; however, no standard strategy has yet been established to achieve a clinical complete response (CR) after CRT. The aim of this study was to clarify when a decision can be made to perform further treatment for a clinical CR. We evaluated 78 patients that underwent an esophagectomy after neoadjuvant CRT in our department between 1998 and 2007. The study investigated the clinical and pathologic results of neoadjuvant CRT. Of the 78 cases, 19 (24.3%) were a pathologic CR (Grade 3). Pathologic CR could be estimated in only 3 of 8 clinical CR cases (37.5%). On the other hand, 12 (20.7%) of the 58 clinical partial response (PR) cases achieved pathologic CR. Likewise, 4 cases (36.4%) achieved pathologic CR among the clinical no change/progressive disease (NC/PD) patients. The clinical evaluation for CRT does not reflect the pathologic effectiveness and, even if clinical CR was achieved, viable cancer cells were still present at the primary site in the majority of the population.

A pilot study of three-cycle consolidation chemotherapy with paclitaxel and platinum in epithelial ovarian cancer patients with clinical complete response after paclitaxel and platinum chemotherapy

The aim of this study is to evaluate the efficacy of three additional cycles of paclitaxel and platinum chemotherapy in epithelial ovarian cancer patients with clinical complete response (CR). Patients with histologically confirmed epithelial ovarian cancer stages II-IV with clinical CR after primary surgery and six cycles of chemotherapy with paclitaxel/platinum entered into the study. Three cycles of paclitaxel/platinum (cisplatin, carboplatin) were administered as a consolidation chemotherapy only in patients who agreed to the informed consent. Patients without further treatment served as controls. A total of 81 patients entered into the study. According to the informed consent, 42 patients were treated by the consolidation chemotherapy, and 39 patients were followed up without further treatment. The median actuarial disease-free survival for the patients with and without consolidation chemotherapy was 25.0 months and 26.0 months, respectively (P= 0.80). The median overall survival is not reached. World Health Organization grade 3-4 toxicities in the consolidation arm were increased but showed no significant differences statistically. Although the sample size is small and not randomized, these results suggest that three cycles of consolidation chemotherapy with paclitaxel/platinum might not provide a favorable outcome in patients with a clinical CR.