Complete Histological Response Research Articles

Early Occurrence of Therapy-Related Acute Myeloid Leukemia (t-AML) with Monocytic Differentiation with Trisomy 8 Cytogenetic Abnormality after Radioactive Iodine (RAI) Treatment for Papillary Thyroid Cancer

Background: Although most t-AML occurs after chemotherapy +/- radiation, exposure to radioactive substances can be implicated, as in nuclear accidents. Thyroid cancer is the most commonly endocrine malignancy. The relative risk of second primary malignancy in thyroid cancer patients is higher in those treated with RAI than those without, with a notable 2.5-fold increase risk of leukemia. The excess leukemia risk is greater in patients < 45 yrs compared with older patients. Recent reviews have attempted to characterize cytogenetic and molecular abnormalities from RAI related t-AML. We present the case of a young woman who developed AML with monocytic differentiation and Trisomy 8 cytogenetic abnormality after RAI treatment for thyroid papillary carcinoma.Case Presentation: A 29-year-old Chinese woman presented with worsening fatigue and menorrhagia over 3 months. Initial workup revealed pancytopenia (WBC 1.7, Hb 8.3, Hct 24, PLT 44, ANC 0.7). She had a history of papillary thyroid carcinoma, classic type, treated with total thyroidectomy followed by RAI ablation with 99 mCi of I-131 2 years prior. She had been without evidence of residual/recurrent disease since then. Her only home medication was Levothyroxine and had no other toxic exposure. Physical exam was unremarkable. Serology was negative for HIV, Hepatitis B or C. Peripheral smear showed decreased WBC count, few circulating blasts, atypical monocytes, and decreased platelets. Bone marrow aspiration and biopsy showed marked hypercellular marrow (100%) replaced by sheets of myeloid appearing-blasts, increased medium/large size CD68+ monoblasts with moderate basophilic vacuolated cytoplasm, as well as promonocytes comprising 90% of nucleated marrow cells. This was consistent with AML with monocytic differentiation. Flow Cytometry confirmed presence of HLA-DR, CD56, CD64, CD2, CD5, CD4, and CD11+ myeloblasts (27% of total cells) with increased CD56+ monocytes (23%). Cytogenetic analysis identified trisomy 8. Molecular testing was negative for FLT3 ITD and FLT3 TKD mutations by PCR, and negative for PML-RARA rearrangement by FISH.The patient was started on induction chemotherapy with cytarabine 100 mg/m2 daily as continuous infusion on days 1-7 + Idarubicin 12 mg/m2 daily for days 1-3 (7+3 regimen). Repeat bone marrow evaluation on day 14 revealed complete histologic and cytogenetic response. She received three cycles of consolidation with high dose cytarabine 3 g/m2. She is presently awaiting identification of a matched donor for allogeneic hematopoietic stem cell transplantation.Discussion: t-AML is a distinct subgroup of AML in 2008 WHO classification for their attributed worse outcome than their de novo counterparts with the same genetic abnormalities [except inv(16)(p13.1q22), t(16;16)(p13.1;q22) or t(15;17)(q22;q12)], suggestive of biologic differences. However, these findings are largely derived from patients who received cytotoxic treatment with topoisomerase II inhibitors, alkylating agents and/or RT. In contrast, little is known about outcome and prognosis in t-AML from RAI. We present a young woman with RAI related t-AML with monocytic differentiation and trisomy 8 after a 2-year latency who responded to standard induction and consolidation chemotherapy. To our knowledge the monocytic differentiation with Trisomy 8 was previously unreported.Retrospective studies and case series suggest that median latency of RAI related t-AML is ~ 7 yrs, in bimodal distribution peaking at 1-3 years and later at 8-10 years. 68% of t-AML from RAI have abnormal karyotype, with chromosomes 7, 5, and 8 most commonly involved, notably del 7q. FAB M2, M3, and M4 represented the vast majority of cases. Compared to patients with other t-AML, RAI-related AML tend to have significantly inferior survival. This suggests a unique mechanism of secondary primary malignancy, possibly via the Na(+)/I(-) symporter, a membrane glycoprotein that mediates active iodide uptake in thyroid and other tissues.Conclusion: t-AML from RAI is an under-recognized and under-reported form of AML, with unclear mechanism, wide-spectrum cytogenetic abnormalities and histology, undefined dose-risk ratio, and decreased survival. As the incidence of thyroid cancer increases, and utilization of RAI becomes more frequent, further investigation is needed to better characterize this unique entity, early detection and its optimal treatment. DisclosuresNo relevant conflicts of interest to declare.

Response to preoperative chemotherapy in patients undergoing resection of pulmonary metastasis from soft tissue sarcoma – a predictor of outcome?

Approximately 50% of patients with high-grade soft tissue sarcoma (STS) will develop pulmonary metastasis. This is the most frequent cause of death and improving treatment is warranted. Preoperative chemotherapy is used for selected patients, usually those with less favorable prognosis and mainly outside clinical trials. The predicted value of histological and radiological response to preoperative chemotherapy on outcome was the main focus for this investigation.Patients and methods. This retrospective study comprises 93 patients with metachronous lung metastasis from STS who underwent complete metastasectomy alone (n = 41) or metastasectomy following preoperative chemotherapy (n = 52). Clinical data, histological and radiological responses to chemotherapy were recorded and survival analyses performed.Results. The time from initial STS diagnosis to the appearance of metastasis was shorter in the preoperative chemotherapy group than in those treated with surgery alone (p = 0.02). However, no statistical differences in post-metastasis disease-specific survival (DSS) or progression-free survival (PFS) between the groups were demonstrated. Patients in the preoperative chemotherapy group with good (complete) histological response had improved PFS compared with poor responders (p = 0.04). Radiological partial response was an independent, favorable prognostic factor for improved PFS and DSS (p = 0.003).Conclusion. Despite having unfavorable disease characteristics, some patients may benefit from preoperative chemotherapy. Both histological and radiological responses to preoperative chemotherapy seem to be prognostic in STS patients undergoing complete pulmonary metastasectomy.

Influence of Pathologic Complete Response to Induction Chemotherapy on Long-Term Survival of Patients Advanced Squamous Cell Carcinoma of the Oral Cavity Tongue

Objective: To discuss long-term efficacy of preoperative induction chemotherapy (IC) plus surgery ± radiotherapy in patients with resectable stage III or IV squamous cell carcinoma of the oral cavity tongue (SCCOT). Methods: From June 1996 to December 2005, 73 patients with advanced SCCOT were treated with IC followed by surgery ± radiotherapy, at the Cancer Center of Sun Yat-sen University. The 5-year overall survival (OS), local control and reasons of treatment failure were analyzed retrospectively. Results: 73 patients aged from 22 to 77 years with untreated, clinical T1–4 N0-2M0 SCCOT underwent IC followed by surgery ± radiotherapy. After IC, 17 patients (23.3%) achieved clinical complete response; 44 patients (60.3%) clinical partial response; 12 patients (16.4%) no response or progression, and overall response rate was 89.0% (65/77). On final surgical pathology, 14 patients (19.2%) achieved histological complete response; 59 patients (80.8%) histological incomplete response. The 5-year OS was 59.8%, local control was 69.9% (51/73). No treatment-associated deaths occurred, and toxicity was modest. Conclusion: IC plus surgery ± radiotherapy was a treatment modality that was tolerated with encouraging survival outcome in advanced resectable SCCOT patients. Response rate with this regimen was limited, but the responders were associated with excellent prognosis.

術前DCF療法が著効した食道原発内分泌細胞癌の１切除例

Esophageal endocrine cell carcinoma is extremely rare. We report a case of esophageal endocrine cell carcinoma showing histological complete response to neoadjuvant chemotherapy with docetaxel/cisplatin/5-fluorouracil (DCF). A 66-year-old man had been experiencing epigastralgia, and a type 2 tumor in the thoracic part of esophagus was detected by upper endoscopy. The biopsy showed endocrine cell carcinoma. PET/CT, endoscopy and an esophagogram showed that the patient had a 70-mm scaled type 2 tumor in the middle thoracic esophagus, and they also revealed lymph node metastases (no. 106recR). We diagnosed a cT3cN1cM0 cStage III tumor. With two courses of DCF treatment, both the primary tumor and lymph node metastases showed a partial response. We performed a subtotal esophagectomy with three-field lymph node dissection. The pathological examination of the resected specimens revealed no malignant cells in the esophagus or lymph nodes, and we concluded that the pathological effect of the DCF treatment was Grade 3.

High Dose Thiotepa in Patients with Relapsed or Refractory Osteosarcomas: Experience of the SFCE Group

Introduction. Osteosarcoma relapse has a poor prognosis, with less than 25% survival at 5 years. We describe the experience of the French Society of Paediatric Oncology (SFCE) with high dose (HD) thiotepa and autologous stem cell transplantation (ASCT) in 45 children with relapsed osteosarcoma. Patients and Methods. Between 1992 and 2004, 53 patients received HD thiotepa (900 mg/m2) followed by ASCT in 6 centres. Eight patients were excluded from analysis, and we retrospectively reviewed the clinical radiological and anatomopathological patterns of the 45 remaining patients. Results. Sixteen girls and 29 boys (median age, 15.9 years) received HD thiotepa after initial progression of metastatic disease (2), first relapse (26), and second or third relapse (17). We report 12 radiological partial responses and 9 of 31 histological complete responses. Thirty-two patients experienced further relapses, and 13 continued in complete remission after surgical resection of the residual disease. Three-year overall survival was 40%, and 3-year progression-free survival was 24%. Delay of relapse (+/− 2 years from diagnosis) was a prognostic factor (P = 0.011). No acute toxic serious adverse event occurred. Conclusion. The use of HD thiotepa and ASCT is feasible in patients with relapsed osteosarcoma. A randomized study for recurrent osteosarcoma between standard salvage chemotherapy and high dose thiotepa with stem cell rescue is ongoing.

Relationship between histologic response and the degree of tumor shrinkage after chemoradiotherapy in patients with locally advanced rectal cancer

Preoperative chemoradiotherapy (CRT) significantly decreases local recurrence in advanced rectal cancer. We studied whether the degree of tumor shrinkage can be used as a predictor of histologic response. The subjects were 114 patients with locally advanced rectal cancer who underwent total mesorectal excision after receiving radiotherapy combined with uracil/tegafur (UFT) or S-1. The degree of tumor shrinkage based on barium enema examination and magnetic resonance imaging (MRI) were assessed before CRT and immediately before surgery. A histologic complete response (ypCR), histologic marked regression, T and N downstaging were associated with significantly higher tumor-shrinkage rates on barium enema (P < 0.01, P < 0.01, P < 0.01, and P < 0.01, respectively) as well as on MRI (P < 0.01, P < 0.01, P < 0.01, and P = 0.01, respectively). On multivariate analysis, ypCR and histologic marked regression were significantly related only to tumor-shrinkage rates on barium enema (P < 0.01 and P < 0.01, respectively), and were not related to tumor-shrinkage rates on MRI. The degree of tumor shrinkage is closely related to the final histologic response. Two-dimensionally evaluated tumor-shrinkage rates based on barium enema are adequate for the prediction of histologic response.

A multicentric randomized controlled trial on the impact of lengthening the interval between neoadjuvant radiochemotherapy and surgery on complete pathological response in rectal cancer (GRECCAR-6 trial): rationale and design

BackgroundNeoadjuvant radiochemotherapy (RCT) is now part of the armamentarium of cancer of the lower and middle rectum. It is recommended in current clinical practice prior to surgical excision if the lesion is classified T3/T4 or N+. Histological complete response, defined by the absence of persistent tumor cell invasion and lymph node (ypT0N0) after pathological examination of surgical specimen has been shown to be an independent prognostic factor of overall survival and disease-free survival. Surgical excision is usually performed between 6 and 8 weeks after completion of CRT and pathological complete response rate ranges around 12%. In retrospective studies, a lengthening of the interval after RCT beyond 10 weeks was found as an independent factor increasing the rate of pathological complete response (between 26% and 31%), with a longer disease-free survival and without increasing the operative morbidity. The aim of the present study is to evaluate in 264 patients the rate of pathological complete response rate of rectal cancer after RCT by lengthening the time between RCT and surgery.Methods/designThe current study is a multicenter randomized trial in two parallel groups comparing 7 and 11 weeks of delay between the end of RCT and cancer surgery of rectal tumors.At the end of the RCT, surgery is planified and randomization is performed after patient’s written consent for participation. The histological complete response (ypT0N0) will be determined with analysis of the complete residual tumor and double reading by two pathologists blinded of the group of inclusion. Patients will be followed in clinics for 5 years after surgery. Participation in this trial does not change patient’s management in terms of treatment, investigations or visits. Secondary endpoints will include overall and disease free survival, rate of sphincter conservation and quality of mesorectal excision. The number of patients needed is 264.Trial registrationClinicalTrial.gov: NCT01648894

Soluble interleukin-6 receptor is a serum biomarker for the response of esophageal carcinoma to neoadjuvant chemoradiotherapy.

Preoperative chemoradiotherapy has been shown to improve the outcome of patients with esophageal cancer, but because response to this therapy varies, it is desirable to identify in advance individuals who would be unlikely to benefit, in order to avoid unnecessary adverse drug effects. The serum profiles of 84 cytokines and related proteins were determined in 37 patients with esophageal squamous cell carcinoma who received identical neoadjuvant preoperative chemoradiotherapy regimens and underwent surgical resection. Histological response to this therapy was assessed in surgically resected specimens. The serum soluble interleukin-6 receptor (sIL6R) level was significantly higher in 30 patients who failed to achieve a histological complete response (P = 0.005). Multivariate analysis revealed that the increased level of sIL6R was one of several significant independent predictors of an unfavorable outcome (hazard ratio, 2.87; P = 0.017). The increased level of this cytokine in patients who did not obtain a complete response was reproducibly observed in an independent cohort of 34 patients. Esophageal squamous cell carcinoma patients with an increased serum level of sIL6R are predicted to respond poorly to preoperative chemoradiotherapy, therefore, their exclusion from this treatment may be considered. Persistent systemic inflammation is implicated as a possible mechanism of resistance to this therapy.

Histological complete response after neoadjuvant XELOX in advanced gastric carcinoma.

We report on a case of a 65-year-old Chinese male with locally advanced gastric adenocarcinoma achieving pathological complete response after neoadjuvant chemotherapy with capecitabine and oxaliplatin (XELOX) regimen. He underwent esophagogastroduodenoscopy, which revealed a 6x5cm gastric ulcer. Biopsy of gastric ulcer revealed adenocarcinoma. Further workups with abdominal enhancement computed tomography (CT) staged his cancer as T4N2M0. He received 2 cycles of neoadjuvant chemotherapy with XELOX without severe toxicity. Afterwards, he underwent curative surgery consisting of total gastrectomy with extended D2 lymph node dissections and a Roux-en-Y esophagojejunostomy. On microscopic examination, no tumor cells were detected in the ulcer scar of the resected stomach and in the regional lymph nodes. The benefit of XELOX regimen as neoadjuvant chemotherapy in gastric cancer is worth further investigation.

Hybrid SPECT/CT imaging of sentinel nodes in esophageal cancer: first results

Sentinel node (SN) biopsy in esophageal cancer has the potential of becoming an important tool for ruling out the presence of lymph node metastases in patients opted for less extensive surgery without neoadjuvant treatment. To investigate preoperative SN imaging in esophageal cancer using hybrid single photon emission computed tomography (SPECT)/CT. Eight patients with esophageal cancer scheduled for thoracoabdominal esophagectomy after neoadjuvant treatment, underwent endoscopic submucosal injection of (99m)Tc-nanocoll the day before surgery, followed by imaging with SPECT/CT for preoperative detection. Intraoperative detection of SNs was performed with a gamma probe. SNs were identified by SPECT/CT in 7/8 cases (88%) and by gamma probe in all cases. The median number of identified lymph node stations with SN in the operating field was 1 (range 0-2) for SPECT/CT and 1 (range 1-3) for gamma probe. The median distance between the perceived location of the respective SN according to SPECT/CT and the location identified with the gamma probe was <5 mm (range <5-15 mm). In one patient who had a complete histologic response to neoadjuvant treatment in the primary tumor, there was one single metastasis that was not contained in one of the SNs. Preoperative identification of sentinel nodes with hybrid SPECT/CT after endoscopic injection of radiocolloid is a technique with obvious potential for SN mapping in esophageal cancer.

Tu1085 Mantle Cell Lymphoma With Gastrointestinal Involvement: Characteristics and Clinical Outcome

Objective: Helicobacter pylori eradication has widely accepted as a primary treatment for gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). We evaluated long-term clinical outcome of low-grade gastric MALT lymphoma in a single center. Methods: From 1996 to 2010, a total of 205 H. pylori-infected patients with lowgrade gastric MALT lymphoma were prospectively enrolled in Seoul National University Hospital. Twelve patients were excluded due to presence of extra-gastric MALT lymphoma or other malignancy at initial diagnosis. Complete remission (CR) was defined as no endoscopic findings of lymphoma, and histopathology of complete histological response (ChR) or probable minimal residual disease (pMRD). Tumor response to H. pylori eradication therapy was evaluated by endoscopy and histopathology every 2-3 months till CR and every 6-12 months after achieving CR. Results: Median follow-up period was 5.4 years (range, 1.0-14.4 years). H. pylori was successfully eradicated in 187 (96.9%) of 193 eligible patients. CR was obtained in 170 (88.1%) patients and the median time to achieve CR was 3 months (range, 1-20 months) after H. pylori eradication therapy. Tumor recurrence was found in 7 (4.1%) patients and the median tumor recurrence time was 13 months (range, 3-61 months) after achieving CR. Cumulative recurrence rate was 1.9, 4.2 and 7.8% at 1, 3 and 5 years, respectively. Disease-free survival was 97.0, 96.1 and 94.8% at 3, 5 and 7 years, respectively. Other malignancies were found in 8 (4.1%) of 193 patients, none of whom had metachronous gastric cancer. Five-year and 10-year overall survival rate was 99.4 and 97.4%, respectively. Tumors of the proximal stomach (mid-body to fundus) (odds ratio [OR] 4.39, 95% confidence interval [CI] 1.34-14.43; p=0.015) and low serum total cholesterol level (,170 mg/dL) (OR 4.17, 95% CI 1.27-13.71; p=0.019) increased the risk of non-CR after H. pylori eradication therapy. Conclusions: Most patients with low-grade gastric MALT lymphoma treated by H. pylori eradication therapy showed excellent long-term outcomes. Serum total cholesterol might be a novel predictive marker for tumor response to H. pylori eradication therapy.

Tu1086 Management Strategy for Small Duodenal Carcinoid Tumors: Does Conservative Management With Close Follow-up Represent an Alternative to Endoscopic Treatment?

Objective: Helicobacter pylori eradication has widely accepted as a primary treatment for gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). We evaluated long-term clinical outcome of low-grade gastric MALT lymphoma in a single center. Methods: From 1996 to 2010, a total of 205 H. pylori-infected patients with lowgrade gastric MALT lymphoma were prospectively enrolled in Seoul National University Hospital. Twelve patients were excluded due to presence of extra-gastric MALT lymphoma or other malignancy at initial diagnosis. Complete remission (CR) was defined as no endoscopic findings of lymphoma, and histopathology of complete histological response (ChR) or probable minimal residual disease (pMRD). Tumor response to H. pylori eradication therapy was evaluated by endoscopy and histopathology every 2-3 months till CR and every 6-12 months after achieving CR. Results: Median follow-up period was 5.4 years (range, 1.0-14.4 years). H. pylori was successfully eradicated in 187 (96.9%) of 193 eligible patients. CR was obtained in 170 (88.1%) patients and the median time to achieve CR was 3 months (range, 1-20 months) after H. pylori eradication therapy. Tumor recurrence was found in 7 (4.1%) patients and the median tumor recurrence time was 13 months (range, 3-61 months) after achieving CR. Cumulative recurrence rate was 1.9, 4.2 and 7.8% at 1, 3 and 5 years, respectively. Disease-free survival was 97.0, 96.1 and 94.8% at 3, 5 and 7 years, respectively. Other malignancies were found in 8 (4.1%) of 193 patients, none of whom had metachronous gastric cancer. Five-year and 10-year overall survival rate was 99.4 and 97.4%, respectively. Tumors of the proximal stomach (mid-body to fundus) (odds ratio [OR] 4.39, 95% confidence interval [CI] 1.34-14.43; p=0.015) and low serum total cholesterol level (,170 mg/dL) (OR 4.17, 95% CI 1.27-13.71; p=0.019) increased the risk of non-CR after H. pylori eradication therapy. Conclusions: Most patients with low-grade gastric MALT lymphoma treated by H. pylori eradication therapy showed excellent long-term outcomes. Serum total cholesterol might be a novel predictive marker for tumor response to H. pylori eradication therapy.

Tu1084 Long-Term Outcome of Low-Grade Gastric Mucosa-Associated Lymphoid Tissue Lymphoma After Helicobacter pylori Eradication Therapy: A Prospective Single Center Study

Objective: Helicobacter pylori eradication has widely accepted as a primary treatment for gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). We evaluated long-term clinical outcome of low-grade gastric MALT lymphoma in a single center. Methods: From 1996 to 2010, a total of 205 H. pylori-infected patients with lowgrade gastric MALT lymphoma were prospectively enrolled in Seoul National University Hospital. Twelve patients were excluded due to presence of extra-gastric MALT lymphoma or other malignancy at initial diagnosis. Complete remission (CR) was defined as no endoscopic findings of lymphoma, and histopathology of complete histological response (ChR) or probable minimal residual disease (pMRD). Tumor response to H. pylori eradication therapy was evaluated by endoscopy and histopathology every 2-3 months till CR and every 6-12 months after achieving CR. Results: Median follow-up period was 5.4 years (range, 1.0-14.4 years). H. pylori was successfully eradicated in 187 (96.9%) of 193 eligible patients. CR was obtained in 170 (88.1%) patients and the median time to achieve CR was 3 months (range, 1-20 months) after H. pylori eradication therapy. Tumor recurrence was found in 7 (4.1%) patients and the median tumor recurrence time was 13 months (range, 3-61 months) after achieving CR. Cumulative recurrence rate was 1.9, 4.2 and 7.8% at 1, 3 and 5 years, respectively. Disease-free survival was 97.0, 96.1 and 94.8% at 3, 5 and 7 years, respectively. Other malignancies were found in 8 (4.1%) of 193 patients, none of whom had metachronous gastric cancer. Five-year and 10-year overall survival rate was 99.4 and 97.4%, respectively. Tumors of the proximal stomach (mid-body to fundus) (odds ratio [OR] 4.39, 95% confidence interval [CI] 1.34-14.43; p=0.015) and low serum total cholesterol level (,170 mg/dL) (OR 4.17, 95% CI 1.27-13.71; p=0.019) increased the risk of non-CR after H. pylori eradication therapy. Conclusions: Most patients with low-grade gastric MALT lymphoma treated by H. pylori eradication therapy showed excellent long-term outcomes. Serum total cholesterol might be a novel predictive marker for tumor response to H. pylori eradication therapy.

Abstract 4565: Whole exome sequencing links MAPK1 mutation to exquisite sensitivity to brief erlotinib monotherapy in head and neck cancer.

Abstract Activating mutations of EGFR, primarily found in a subgroup of lung cancers, serve as predictive biomarkers for EGFR tyrosine kinase inhibitor (TKI) sensitivity. Clinical responses to EGFR TKIs in other cancers are only moderate and predictive biomarkers are lacking. Here, we report a head and neck cancer patient with no EGFR genetic alterations, who experienced a complete histologic clinical response after 14 days of erlotinib monotherapy on a window-of-opportunity presurgical trial. To determine the somatic genetic events underlying the extraordinary and unexpected response to erlotinib alone, whole exome sequencing was performed. A bi-allelic missense mutation of MAPK1(E322K) was detected in the tumor in the absence of other mutations reported to be correlated with EGFR TKI sensitivity in preclinical models or cancer patients. Combined bioinformatics analyses of genomics-drug databases revealed, for the first time, that loss-of-function of MAPK1 or MAPK1 mutation correlates with erlotinib sensitivity. Functional studies confirmed heightened sensitivity to erlotinib by loss-of-function of MAPK1 in HNSCC cells. Our preliminary findings suggest that this MAPK1 mutation, which is also found at low frequencies in HNSCC and cervical cancers, may identify a subgroup of cancer patients who may be cured with EGFR TKI monotherapy. Citation Format: Vivian WY Lui, Eliezer Van Allen, Hua Li, Fan Zhang, Yan Zeng, Jonas T. Johnson, Levi A. Garraway, Gordon B. Mills, Jennifer Rubin Grandis. Whole exome sequencing links MAPK1 mutation to exquisite sensitivity to brief erlotinib monotherapy in head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4565. doi:10.1158/1538-7445.AM2013-4565

Photodynamic Therapy with Ablative Carbon Dioxide Fractional Laser for Treating Bowen Disease

BackgroundTopical photodynamic therapy (PDT) has been increasingly used to treat malignant skin tumors including the Bowen disease. However, patients could be displeased with the long incubation time required for conventional PDT.ObjectiveWe evaluated the efficacy and safety of PDT with a short incubation time of ablative CO2 fractional laser pretreatment for treating Bowen disease.MethodsTen patients were included. Just before applying the topical photosensitizer, all lesions were treated with ablative CO2 fractional laser, following the application of methyl aminolevulinate and irradiation with red light (Aktilite CL 128). Histological confirmation, rebiopsy, and clinical assessments were performed. Adverse events were also recorded.ResultsFive of the ten (50%) lesions showed a complete response (CR) within three PDT sessions. After four treatment sessions, all lesions except one penile shaft lesion (90%) achieved clinical and histological CR or clinical CR only. The average number of treatments to CR was 3.70±1.70. The treatments showed favorable cosmetic outcomes and no serious adverse events.ConclusionThe results suggest that pretreatment with an ablative fractional CO2 laser before PDT has similar treatment efficacy and requires a shorter photosensitizer incubation time compared with the conventional PDT method.

18-Year-Old Woman with an Embryonal Rhabdomyosarcoma of the Uterus in Statu Nascendi.

Background: We report a case of an 18-year-old woman with an embryonal rhabdomyosarcoma in statu nascendi. Case: A fist-sized embryonal rhabdomyosarcoma of the uterus filling the vaginal vault was diagnosed in an adolescent with virgo intacta suffering from therapy resistant vaginal discharge, bleeding and bulging mass for six months. Further imaging revealed one suspicious pelvine lymph node. Excision of the tumour including the intracervical stalk was performed and followed by systemic multiagent chemotherapy. PET-CT scan presented a complete response after the third cycle. Histological complete response was shown by laparoscopic dissection of regional pelvic lymph nodes and curettage. Conclusion: Uterine Rhabdomyosarcoma should be considered as differential diagnosis of therapy resistant vaginal flour and bleeding in young women. Fertility-sparing therapy is possible in selected exceptional cases.

Pre-operative chemoradiation followed by post-operative adjuvant therapy with tetrathiomolybdate, a novel copper chelator, for patients with resectable esophageal cancer

Introduction This phase II trial investigated chemoradiation followed by surgery and 2years of adjuvant tetrathiomolybdate (TM) for resectable esophageal cancer. Methods Patients with resectable, locally advanced esophageal cancer received neoadjuvant cisplatin 60mg/m(2) (days 1 and 22), paclitaxel 60mg/m(2) (days 1, 8, 15, and 22), and 45Gy hyperfractionated radiotherapy for 3weeks followed by transhiatal esophagectomy. TM 20mg PO QD was started 4weeks post-op, and continued for 2years to maintain the ceruloplasmin level between 5 and 15mg/dl. Results Sixty-nine patients were enrolled (median age, 60years). Sixty-six patients underwent surgery and 61 patients had a complete resection. Histologic complete response rate was 10%. Twenty-one patients did not receive TM (metastases noted in the peri-operative period, prolonged post-operative recovery time, or patient refusal). Forty-eight patients started TM; 14 completed 24months of treatment, 11 completed 10-18months, 15 completed 2-8months, and 8 completed ≤1month. Twenty-seven patients had disease recurrence. With a median follow-up of 55months, 25 patients were alive without disease, 1 was alive with disease, and 43 have died. Three-year recurrence-free survival was 44% (95% CI, 32-55%) and the three-year overall survival was 45% (95% CI 33-56%). Conclusions TM is an antiangiogenic agent that is well tolerated in the adjuvant setting. Disease-free survival and overall survival are promising when compared to historical controls treated at our institution with a similar regimen that did not include TM. However, the challenges associated with prolonged administration limit further investigation.

Interstitial preoperative high-dose-rate brachytherapy for early stage cervical cancer: Dose–volume histogram parameters, pathologic response and early clinical outcome

To analyze dose-volume histogram parameters and pathologic response after preoperative high-dose-rate brachytherapy (HDRB) for high-risk early stage cervical cancers (ESCCs). From June 2007 to December 2011, 32 patients with a histologically proven invasive cervical cancer with high risk of local recurrence (size >2cm, adenocarcinoma type, perineural and/or lymphovascular invasion) underwent a preoperative HDRB, which delivered a total dose of 39Gy in nine fractions over 5 days. All the patients underwent hysterectomy after HDRB. With a median clinical target volume of 50cc (minimum-maximum, 42-74), the median V100 was 49cc (minimum-maximum, 42-50). Median D90 was 45Gy (equivalent dose at 2Gy per fraction, 56Gyαβ10). Median D2cc was 34Gy, 31Gy, 28Gy, and 38Gyαβ3 for bladder, rectum, sigmoid, and vagina, respectively. Twenty-eight patients (88.5%) achieved a complete histologic response after surgery, whereas for the 4 remaining patients, residual tumor cells (3 patients) and gross residual disease (1 patient) were observed in the pathologic specimen. With a median followup of 24 months (minimum-maximum, 5-48), no local recurrence was observed; 1 patient died of intercurrent cause. Early toxicity occurred within the 30 days after HDRB (Common Terminology Criteria for Adverse Events v3.0) was G1 diarrhea for 15 patients (47%) and G1 urinary frequency or urgency for 13 patients (40.6%). No G2-G3 toxicities were noticed. Preoperative HDRB for high-risk ESCCs represents a well-tolerated procedure, which leads to a high rate of postoperative pathologic response. Dose-volume histogram parameters were at least equivalent to those obtained with a low-dose-rate procedure. Long-term results will help to analyze the place of preoperative brachytherapy in the management of high-risk ESCCs.

Swallowed Fluticasone Improves Histologic but Not Symptomatic Response of Adults With Eosinophilic Esophagitis

We evaluated the effect of aerosolized fluticasone therapy on symptomatic dysphagia and histologic eosinophilia in adults with eosinophilic esophagitis (EoE). We performed a double-blind, randomized, placebo-controlled trial of fluticasone in 42 adult patients with a new diagnosis of EoE (30 men; mean age, 37.5 y). Participants were assigned randomly to groups that swallowed 880 μg of aerosolized fluticasone twice daily (n = 21), or took a placebo inhaler twice daily (n = 15) for 6 weeks. End points of the study were symptomatic and histologic response. A complete histologic response (>90% decrease in mean eosinophil count) was observed in 11 of 15 subjects who received 6 weeks of fluticasone (62%), compared with none of the 15 subjects who received placebo (P < .001), based on intention-to-treat analysis; histologic responses were observed in 68% of subjects who received fluticasone (13 of 19) compared with none of those who received placebo (0 of 15) by per-protocol analysis (P < .001). Intracellular staining for eosinophil-derived neurotoxin was reduced in 81% of subjects who received fluticasone (13 of 16) compared with 8% who received placebo (1 of 13) (P < .001). Dysphagia was reduced in 57% of subjects who received fluticasone (12 of 21) compared with 33% who received placebo (7 of 21) (P = .22) by intention-to-treat analysis; dysphagia was reduced in 63% of patients who received fluticasone (12 of 19) and 47% of those who received placebo (7 of 15) (P = .49) based on per-protocol analysis. Esophageal candidiasis developed in 26% of subjects who received fluticasone (5 of 19), but in none of the subjects in the placebo group (P = .05). Aerosolized, swallowed fluticasone leads to a histologic but not a symptomatic response in adults with EoE.

Systemic Chemotherapy prior to Cytoreductive Surgery and HIPEC for Carcinomatosis from Appendix Cancer: Impact on Perioperative Outcomes and Short-Term Survival

Background and Objectives. Systemic chemotherapy administered prior to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mucinous adenocarcinoma of appendiceal origin (PMCA) is associated with a significant rate of histological response. The impact of preoperative systemic chemotherapy (PSC) on intraperitoneal tumor burden, completeness of cytoreduction, and perioperative complications is unknown. Methods. We analyzed prospectively collected data from our HIPEC database. Thirty-four patients with PMCA were prospectively recruited and treated with PSC. Perioperative variables and survival in this group of patients were compared against 24 patients with PMCA who did not receive PSC. Results. Ten of 34 patients (29%) receiving PSC had a complete or near complete histological response. Patients receiving PSC had a lower peritoneal carcinomatosis index, required fewer peritonectomies and visceral resections, and achieved complete cytoreduction more frequently compared to patients with no preoperative chemotherapy. The incidence of perioperative complications and survival were not significantly different between the two groups. However, patients with complete histological response had better overall survival compared to patients without complete response. Conclusions. Preoperative systemic chemotherapy in appendix-originated PMCA is associated with a significant rate of histological response which may reduce the tumor burden, facilitate less aggressive and more complete CRS, and improve short-term survival in patients with a significant histological response.