Higher Disease-free Survival Rate Research Articles

Insights into Tumor-Associated Tertiary Lymphoid Structures: Novel Targets for Antitumor Immunity and Cancer Immunotherapy.

Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates that phenotypically resemble conventional secondary lymphoid organs and are commonly found at sites of chronic inflammation. They are also found in a wide variety of primary and metastatic human tumors. The presence of tumor-associated TLS (TA-TLS) is associated with prolonged patient survival, higher rates of disease-free survival, and a favorable response to current cancer therapies. However, the immune responses that occur in these structures, and how they contribute to improved clinical outcomes, remain incompletely understood. In addition, it is unknown how heterogeneity in TA-TLS cellular composition, structural organization, and anatomic location influences their functionality and prognostic significance. Understanding more about TA-TLS development, formation, and function may offer new therapeutic options to modulate antitumor immunity.

Sequential chemoradiation versus radiation alone or concurrent chemoradiation in adjuvant treatment after radical hysterectomy for stage IB1-IIA2 cervical cancer (STARS Study): A randomized, controlled, open-label, phase III trial.

6007 Background: There are limited data from previous studies regarding whether the addition of chemotherapy to adjuvant radiation after radical surgery improves outcomes among patients with early-stage cervical cancer and adverse pathological factors. Methods: This was a prospective randomized trial including patients with FIGO 2009 stage IB1-IIA2 cervical cancer and squamous-cell, adenocarcinoma, or adenosquamous carcinoma with at least one adverse factor after radical hysterectomy. Patients were randomized 1:1:1 to receive adjuvant radiation alone, concurrent chemoradiation with weekly cisplatin (30-40 mg/m2), or sequential chemoradiation with cisplatin (60-75 mg/m2) plus paclitaxel (135-175 mg/m2) in 21 day cycles, given 2 cycles before and 2 cycles after radiotherapy respectively. The primary outcome was the rate of disease-free survival at 3 years. Results: A total of 1,048 patients were included in the study (350, radiation alone; 345, concurrent chemoradiation; and 353, sequential chemoradiation). Overall, the median follow-up was 56 months and the median age of patients was 48 years. Most patients (75%) had stage IB1 or IIA1 disease. The three groups were similar with respect to histologic subtypes, the rate of lymphovascular invasion, parametrial, surgical margin and deep stromal involvement, tumor grade, rate of use of minimally invasive surgery, and neoadjuvant chemotherapy, except for lymph-node involvement that was lowest in radiation alone arm. In the intention-to-treat population, sequential chemoradiation was associated with a higher rate of disease-free survival than radiation alone (3-year rate, 90·0% vs. 82·0%; HR 0·52; 95% CI, 0·35 to 0·76) and concurrent chemoradiation (90·0% vs. 85·0%; HR 0·65; 95% CI, 0·44 to 0·96), differences remained after adjustment for lymph-node involvement. Sequential chemoradiation was also associated with a higher rate of overall survival than radiation alone (5-year rate, 92·0% vs. 88·0%; HR for death from cancer, 0·58; 95% CI, 0·35 to 0·95). However, neither disease-free survival nor cancer death risk was different between patients treated with concurrent chemoradiation or radiation alone. Conclusions: In this trial, sequential chemoradiation, rather than concurrent chemoradiation, resulted in a higher disease-free survival and lower risk of cancer death than radiation alone among women with early-stage cervical cancer after radical surgery. Clinical trial information: NCT00806117.

Transanal total mesorectal excision in the prone jackknife position without being conscious of the size of prostatic enlargement for lower rectal cancer.

In 1982, it was demonstrated that a total mesorectal excision alone could achieve low rectal cancer recurrence rates in the pelvis and high disease-free survival rates. Nowadays, the total mesorectal excision is the gold-standard surgery for rectal cancer. Currently, the transanal total mesorectal excision has attracted attention as a promising alternative to the anterior approach. The transanal approach is superior to the anterior approach, because it facilitates total mesorectal excisions of the lower rectum, improves visualization, and shortens the surgical time. Some factors are particularly favorable for the transanal approach, including lesions in the lower third of the rectum, a narrow pelvis, a large tumor, male sex, and a prostatic enlargement. The transanal total mesorectal excision is commonly performed in the Lloyd-Davies position. However, in the Lloyd-Davies position, the sacral bone prevents the mobilized rectum from moving away from the pelvic base. From the perspective of pelvic morphology, we reasoned that, in the prone jackknife position, the mobilized rectum could spontaneously move toward the head, due to gravity, and this would broaden the pelvic surgical field. Consequently, this position could facilitate the transanal total mesorectal excision. Here, we described a transanal total mesorectal excision performed in the prone jackknife position for treating lower rectal cancer with a prostatic enlargement.

Prophylactic HIPEC with radical D2 gastrectomy improves survival and peritoneal recurrence rates for locally advanced gastric cancer: personal experience from a randomized case control study

BackgroundTo investigate the implications of prophylactic intraoperative Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with D2 radical gastrectomy for locally advanced Gastric Cancer (AGC) in a randomized case control study.MethodEighty consecutive patients with locally AGC were randomly separated into 2 groups: HIPEC group (Curative Resection + intraoperative HIPEC with cisplatin 50 mg/m2 at 42.0 ± 1.0 °C for 60 min) and Control group (Curative Resection only). Intraoperative and post-operative events, clinical recovery, morbidity and the disease-free survival (DFS) rates were closely monitored.ResultsFaster recovery of bowel function (43 ± 5 h vs 68 ± 7, P < 0.05) and shorter postoperative stay (8d vs 14d, P < 0.05) were noted in the HIPEC group. Among the 40 HIPEC group patients, the highest intracranial temperature recorded during the procedure was 38.2 °C but the patient made an eventless recovery. Mild renal dysfunction, hyperbilirubinemia and mild liver dysfunction were recorded in the HIPEC group but their incidences were found to be statistically insignificant when compared with the control group (P > 0.05). The 3 year DFS rate analysis showed that the prophylactic HIPEC group had a higher DFS rate (93% vs 65%, P = 0.0054). The peritoneal recurrence rate was lower in the HIPEC group (3% vs 23%, P < 0.05).ConclusionProphylactic HIPEC with radical D2 Gastrectomy improves survival and peritoneal recurrence rates for AGC with favorable post-operative recovery at low and acceptable morbidity.

Retrospective comparison of outcomes of laparoscopic and open surgery for T2 gallbladder cancer – Thirteen-year experience

BackgroundThe objective of this retrospective study is to compare the outcomes of laparoscopic and open surgery for T2 gallbladder cancer (GBC) performed at our hospital for last 13 years. MethodsOf 247 GBC patients who were treated at our hospital between Apr 2004 and Apr 2017, 151 patients with pathologic stage T2 were reviewed. Patients were divided into laparoscopic surgery group (LS group) and open (OS group). Medical recordings were reviewed to check perioperative outcomes, overall survival rates, and disease free survival rates. ResultsFifty-five patients in LS group and 44 in OS met the inclusion criteria. Incidences of postoperative complication were similar between two groups (12.7% vs 13.6%, p = 1.000). Average postoperative hospital stay was significantly shorter in LS group (5.8 vs 9.5 days, p < 0.001). LS group showed significantly higher disease free survival rate (p = 0.0171). There was no significant difference in terms of disease free survival between T2N0 (p = 0.107) and T2N1 patients (p = 0.969) of LS group and OS group. In terms of overall survival rate there was no significant difference (p = 0.116). Overall survival rate was also not significantly different between T2N0 (p = 0.0941) and T2N1 (p = 0.579) patients of LS group and OS group. ConclusionsLaparoscopic approach for treatment of T2 GBC was comparable to open approach in terms of disease free survival, overall survival and complication rate. Further prospective study with higher number of patients should be done to confirm this result in the future.

Abstract GS3-04: A prospective randomized multi-center open-label phase III trial of extending aromatase-inhibitor adjuvant therapy to 10 years - Results from 1697 postmenopausal women in the N-SAS BC 05 trial: Arimidex extended adjuvant randomized study (AERAS)

Abstract Background: Treatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy for 2-3 years is the treatment of choice for hormone-receptor-positive breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may reduce the risk of breast cancer recurrence. Methods: We conducted a prospective randomized multi-center open-label phase III trial to assess the effect of the extended use of anastrozole for an additional 5 years. Postmenopausal patients with stageI-III, hormone-receptor-positive breast cancer, disease-free after 5 years of either anastrozole alone or tamoxifen 2-3 years followed by anastrozole 3-2 years were randomized to continual group with anastrozole for an additional 5 years or stop group without an additional anastrozole. Our primary end point was disease-free survival. Results: We enrolled 1697 women. After a median follow up of 4.9 years, there were 149 events involving disease recurrence or the occurrence of contralateral breast cancer (51 in continual group and 98 in stop group) and 7 deaths (3 in continual group and 4 in stop group). The 5-year disease-free survival rate was 91.9% (95% confidence interval [CI], 89.4 to 93.8) in continual group and 84.4% (95% CI: 80.0 to 88.0) in stop group (hazard ratio for disease-free survival,0.548 ;P=0.0004. by a two-sided log-rank test stratified according to nodal status, prior adjuvant chemotherapy, institution, and choice of anastrozole or tamoxifen). The rate of 5-year overall survival was 99.5% in continual group and 99.6% in stop group. (hazard ratio,1.389 ;P=0.665). The rate of 5-year distant disease-free survival was 97.2% in continual group and 94.3% in stop group (hazard ratio,0.514 ;P=0.0077). Bone-related adverse events were observed more frequently among patients in continual group than among patients in stop group, including a higher incidence of bone pain, stiff joints, bone fractures, and new-onset osteoporosis. Conclusion: The extension of treatment with an adjuvant aromatase inhibitor (anastrozole) to 10 years resulted in significantly higher rates of disease-free survival and distant disease-free survival than those with no additional anastrozole, but the rate of overall survival was not different between two groups. Our study shows that it is safe and beneficial for postmenopausal patients with hormone-receptor-positive breast cancer to take an anastrozole as adjuvant therapy for an additional 5 years after initial treatment. (UMIN:000000818) Citation Format: Ohtani S, Iijima K, Higaki K, Sato Y, Hozumi Y, Hasegawa Y, Takei H, Tanaka M, Yagata H, Masuoka H, Tanabe M, Egawa C, Komoike Y, Saji S, Nakamura T, Yanagita Y, Ohtsu H, Mukai H, Iwase T. A prospective randomized multi-center open-label phase III trial of extending aromatase-inhibitor adjuvant therapy to 10 years - Results from 1697 postmenopausal women in the N-SAS BC 05 trial: Arimidex extended adjuvant randomized study (AERAS) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS3-04.

Outcomes for Invasive Melanomas Treated With Mohs Micrographic Surgery: A Retrospective Cohort Study.

Mohs micrographic surgery (MMS) has been used effectively to treat invasive melanoma. To further study the safety and efficacy of MMS in the treatment of invasive melanoma. A retrospective cohort study evaluated 123 melanomas excised using MMS with MART-1 immunostain. Local recurrence, metastasis, overall survival, and disease-free survival rates were calculated. These were compared with historical controls. Among included patients, 78 were men (63%) and 45 were women (37%), with a mean age of 66.48 years. Mean follow-up time was 1,273 days (3.49 years). Local recurrence was identified in 2/123 (1.63%; 95% confidence interval, 0.20%-5.75%) lesions. Local recurrence was identified in 1/70 (1.43%; 95% confidence interval, 0.04%-7.70%) of head and neck cases. Tumor location was head and neck in 70 lesions (56.9%). Overall survival was 95.12% and disease-specific survival was 100%. Mohs micrographic surgery is an effective treatment method for invasive melanoma, as evidenced by low recurrence rates and high rates of disease-free survival.

Concomitant dose escalation with image-guided Tomotherapy in locally advanced mid-low rectal cancer: a single-center study.

PurposeThe purpose of this study was to evaluate the efficacy and toxicity of concomitant dose-escalated Tomotherapy in locally advanced mid–low rectal cancer.Patients and methodsPatients with locally advanced (T3/T4 or N+), low–mid (≤10 cm from anal verge) rectal carcinoma treated with neoadjuvant chemoradiotherapy followed by surgery between May 2012 and October 2017 in Peking Union Medical College Hospital were included in this study. A dose of 45/50 Gy in 25 fractions was delivered to the pelvis with Tomotherapy, and 55 Gy was prescribed for the primary tumor with a simultaneous, integrated boost. Megavolt computed tomography was performed before every delivery. The concurrent chemotherapy regimen included capecitabine alone and XELOX.ResultsA total of 141 patients were enrolled; 129 patients (91.5%) had stage cT3 or cT4, and 121 patients (85.8%) had positive lymph nodes. The location of the tumors was in the lower rectum in 88 patients (62.4%). After neoadjuvant chemoradiotherapy, 113 patients (80.1%) underwent sphincter-preserving resection. Downstaging was observed in 121 patients (85.8%), including 80 patients (56.7%) with T downstaging and 101 patients (83.5%) with N downstaging. Thirty-two patients (22.7%) obtained pathological complete response (pCR). The median follow-up was 38.5 months (range, 9.3–73.6 months). Only 36 patients (25.5%) experienced treatment failure, including distant metastasis in 29 patients (20.6%) and pelvic recurrent in 7 patients (5.0%). The estimated 5-year overall survival (OS), disease-free survival (DFS), and local control (LC) rates of patients were 75.1%, 70.9%, and 95.5%, respectively. pCR was an independent prognostic factor for DFS (HR 0.13, 95% CI: 0.02–0.93, P = 0.043), but it did not improve OS or LC. Grade 3 or greater acute leukopenia and diarrhea rates were 5.7% and 7.8%, respectively, and 15 patients (10.6%) developed postoperative complications.ConclusionThis study indicates that neoadjuvant, image-guided Tomotherapy with 55 Gy boosted to the primary tumor was well tolerated and resulted in high rates of sphincter-preserving surgery, pCR, LC, and DFS for locally advanced rectal cancer.

Dedifferentiated chondrosarcoma of the pelvis: clinical outcomes and current treatment

BackgroundDedifferentiated chondrosarcomas (CS) are a high-grade variant of CS that confers a 5-year survival of around 10–24%. Dedifferentiated CS arising from the pelvis confers an even worse prognosis.Questions(1) What is the prognosis of patients with dedifferentiated CS of the pelvis? (2) Do wide margins or type of surgical intervention influence outcome? (3) Does the use of adjuvant therapy affect outcome?MethodsPatients were retrospectively reviewed from a prospectively collated musculoskeletal oncology database from 1995 to 2016. Thirty-one cases of dedifferentiated CS arising from the pelvis were included. Wide margins were defined as greater than 4 mm. The mean age was 55.6 years (range 33 to 76 years) and there were 19 males (61.3%) and 12 females (38.7%).ResultsThe disease presented at a locally or systemically advanced stage in 13 patients (41.9%). Eighteen patients (58.1%) underwent surgery with curative intent. Overall survival at 12 months was 15.4% for patients treated with palliative intent and 50% for those treated with surgery. In the surgical group, there were higher rates of disease-free survival in patients who underwent hindquarter amputation and those who received wide surgical margins (p = 0.047 and p = 0.019, respectively). Those who underwent hindquarter amputation were more likely to achieve wide margins (p = 0.05). Time to recurrent disease (local or systemic) was always less than 24 months. No hindquarter amputation for recurrent disease resulted in disease-free survival. No patient who received adjuvant therapy for palliative or recurrent disease had disease control.ConclusionsPelvic dedifferentiated CS often presents at an advanced local or systemic stage and confers a poor prognosis. Achieving wide surgical margins (> 4 mm) provided the highest rate of long-term disease-free survival. Failing to achieve wide margins results in rapid disease recurrence, conferring deleterious consequences.

THE VALUE OF PROGNOSTIC FACTORS FOR GLIOBLASTOMA TREATED WITH CONCURRENT THERMOCHEMORADIOTHERAPY

The treatment of patients with glioblastoma continues to be one of the greatest challenges. Glioblastoma is the most aggressive malignant primary brain tumor and is the most lethal among all cancers. Despite advances in the standard treatment, the prognosis for patients with glioblastoma remains poor, therefore, the development of novel treatment strategies is required.Material and methods.Our study included 30 patients with newly diagnosed glioblastoma, who underwent concurrent chemoradiotherapy and local hyperthermia.Results.The median disease-free and overall survival rates were 9.6 months and 23 months, respectively. The analysis of clinical, molecular-genetic and prognostic factors related to treatment modality showed statistically significant differences in survival between patient groups representing different times for starting adjuvant therapy after surgery. The median disease-free survival was significantly higher in patients who received chemoradiotherapy with local hyperthermia within 6 weeks after surgery than in patients who started adjuvant treatment earlier. The overall survival rate was statistically higher in patients receiving a special treatment for tumor recurrence compared to that in patients receiving symptomatic therapy. The evaluation of molecular-genetic prognostic factors showed no statistically significant differences in survival among patients with methylated and nonmethylated MGMT promoter. The presence of IDH1 mutations was identified in only one case. Evaluation of prognostic factors does not allow identification of clinical and molecular biological factors that group patients with hypersensitivity to the proposed treatment regimen. However, high rates of overall and disease-free survival, even in patients with non-methylated MGMT, allow us to recommend this treatment modality for patients with newly diagnosed glioblastoma.

REDUCING GASTROINTESTINAL EFFECTS OF RADIOTHERAPY ON PRIMARY PELVIC CANCER.

Background Radiotherapy is an effective and key treatment for cancer, but pelvic radiotherapy can damage the gastrointestinal tract and result in distressing acute and long-term effects.1 Pelvic radiotherapy is used either alone, or in combination with surgery and/or chemotherapy as treatment for gynaecological, urological and gastrointestinal cancers. Inevitably, the normal tissues surrounding the cancer is exposed to radiation, with up to 90% of patients reporting a permanent change in bowel habits, and up to two-thirds of patients reporting negative symptoms including: sexual dysfunction; faecal incontinence, urgency, rectal bleeding and chronic pain. Given the high disease free survival rates now achievable in many cancers, addressing quality of life in survivorship for these patients is essential. A range of different strategies are proposed to reduce the effects of radiotherapy on normal tissue, and thus prevent or mitigate the adverse effects. These include technique to improve the delivery of radiotherapy to avoid normal tissues, using CT imaging to guide treatment, use of brachytherapy to place radioactive seeds within the tumour, and adjusting positions and timing the radiotherapy treatment. Other interventions are proposed such as surgically placing slings to transpose the small bowel, pharmacological agents that may protect the mucosal lining of the gastro-intestinal tract, and non-pharmacological interventions including dietary modifications. At the time of radiotherapy treatment, focus is often on disease control and patients may be unware of the potential long-term consequences, and the options that may be available to them. Informed nurses who are able to provide evidence based information at this time can make a pivotal contribution to their care.

Importance of Early Diagnosis of Gastrointestinal Stromal Tumors of the Stomach: Our 5-Year, Single-Center Experience

Objective:The aim of this study was to investigate clinicopathologic characteristics, diagnosis, treatment, and prognosis of patients who underwent surgery with a diagnosis of a gastrointestinal stromal tumor (GIST) of the stomach.Methods:In this single center study, the data of a total of 42 patients diagnosed with a GIST of the stomach in our center between 2010 and 2015 were retrospectively analyzed. The mean age was 60.6 years, with a male-to-female ratio of 1.47/1. Patients presented with various complaints (21 patients had stomach pain,14 patients were asymptomatic, 3 patients had hemorrhage, 2 patients had heartburn and acidity,1 patient had intumescence,1 patient had nausea and vomiting), and all patients underwent surgery. The initial diagnosis was made with endoscopy in 19 patients, with computed tomography in 21 patients, and with magnetic resonance imaging in 2 patients. Local excision or wedge resection was performed in 27 patients, whereas subtotal gastrectomy was performed in 15 patients.Results:The mean tumor diameter was 5.66 cm. Pathologically, 25 patients had very low, 5 patients had low, 6 patients had moderate, and 6 patients had high-grade malignancy. The patients with moderate- to high-grade malignancy received imatinib. Liver metastasis occurred in 2 patients. The mean follow-up was 33 months. The mean disease-free survival time was 31.72 months, and the mean disease-specific (n = 2) survival time was 31.25 months. All patients including metastatic ones were still alive.Conclusions:Our study results show that frequent use of imaging studies and increased use of endoscopic scans for various reasons may increase the rate of incidentally detected gastric stromal tumors. High rates of disease-free survival can be achieved in GIST patients who are in the low-risk group due to the early diagnosis.

Early diagnosis of radiotherapy failure for patients with head and neck cancer: the role of biochemical markers.

There is a lack of effective diagnostic tools for early assessment of radiotherapy (RT) outcome in patients with head and neck cancer (HNC). The timely diagnosis of treatment failure may facilitate use of salvage procedures to prevent disease progression. We assessed squamous cell carcinoma antigen and CYFRA 21-1 as early markers of radiotherapy failure in patients with HNC. Between January 2009 and February 2012, 185 patients (median age 59 years) with squamous cell carcinoma were treated with curative intent with RT alone or combined with chemotherapy (ChT). Markers were estimated in the serum 2 times: before RT and after completion of treatment. The median of follow-up was 40 months. Locoregional control (LRC) was 53% and locoregional failure (LRF) was 31%. When comparing LRC and LRF, there were no significant differences between markers concentration obtained before RT. After RT, CYFRA 21-1 (p = 0.018) was significantly elevated in the LRF group. Patients with CYFRA 21-1 <1.79 ng/mL had a higher disease-free survival rate compared to patients with CYFRA 21-1 ≥1.79 ng/mL (74% vs 53%, respectively). After RT, CYFRA 21-1 was significantly related to the overall survival ratio in both univariate (p = 0.049) and multivariate analysis (p = 0.019). CYFRA 21-1 assessed at the end of RT or ChT seems to be a prognostic marker for tumor response. A high concentration of CYFRA 21-1 after treatment increases the risk of death. CYFRA 21-1 might be suggested in the monitoring of carcinomas of HNC.

Is completion axillary lymph node dissection necessary in patients who are underrepresented in the ACOSOG Z0011 trial?

PurposeThe American College of Surgeons Oncology Group trial Z0011 demonstrated that axillary node dissection (ALND) can be omitted in patients managed with breast conserving surgery and 1 to 2 positive sentinel lymph nodes (SLNs) without adverse effects on locoregional recurrence or disease-free survival (DFS). We investigated patients with breast cancer for whom clinicopathologic features were underrepresented in the Z0011 trial and analyzed radiation therapy treatment patterns and clinical outcomes. Methods and materialsWe retrospectively reviewed records of patients who underwent a lumpectomy and SLN biopsy with positive SLNs but not an ALND and completed adjuvant radiation therapy. Eligible patients had T3 tumors, >2 positive SLNs, invasive lobular carcinoma, estrogen receptor negative status, extranodal extension, Nottingham Grade 3, or were age <50 years. ResultsWe identified 105 women treated between July 2011 and July 2016 with a median follow-up time of 48.5 months (Range, 11-83 months). There were 40 women with an extranodal extension (38.9%) and 42 women with grade 3 disease (40.0%). Nineteen patients received whole breast irradiation alone (18.1%) and 86 patients were treated with modified tangent fields including the superior axilla level I/II (81.9%). Thirty-three patients (31.4%) also received a 3rd supraclavicular, nodal-directed field. Among the 86 patients who received axillary nodal irradiation, nodal volume contouring was performed in 77 patients (89.5%). Fifty-one patients (48.6%) also received adjuvant chemotherapy. The overall rates of 4-year DFS and locoregional control (LRC) were 94.3% and 98.1%, respectively. Off all patients, 1 patient experienced an internal mammary nodal recurrence, another patient a contralateral breast tumor, and two patients distant metastases. There were no axillary or ipsilateral breast tumor recurrences. ConclusionsThis retrospective analysis of women who were underrepresented or excluded from the Z11 trial and underwent a lumpectomy and SLN biopsy with positive SLNs demonstrated comparable rates of LRC and DFS. The high rates of LRC and DFS suggest that completion ALND may be safely omitted in this patient population but larger data sets and longer follow-up times are needed to confirm this finding.

Final Safety Results of a Phase 1 Clinical Trial of Afatinib in Combination With Docetaxel and Postoperative Radiation Therapy for High-Risk Squamous Cell Carcinoma of the Head and Neck

Afatinib is an oral, irreversible EGFR/ErbB family receptor inhibitor with clinical activity in recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). Previously, EGFR-inhibition with cetuximab in combination with docetaxel and postoperative radiation therapy (PORT) was shown in RTOG 0234 to be well tolerated with higher rates of disease-free survival compared to historical results with cisplatin and PORT. We therefore aimed to assess the tolerability of afatinib in combination with docetaxel and PORT in a cohort of patients with high-risk pathologic features after definitive surgery. This was an open label, non-randomized, phase 1, 3+3 dose-escalation study. Eligible patients had resected stage III-IV SCCHN of the oral cavity, oropharynx, larynx, or hypopharynx with high-risk features of either positive margins (tumor at ink), extracapsular nodal extension, N3 nodal stage, or T4 tumor with bone invasion. Patients received afatinib at an initial dose of 30 mg daily for 1 week prior to PORT and then daily during PORT. Docetaxel 15 mg/m2 was given weekly during PORT. The maximum PORT dose was 66 Gy, 2 Gy/fraction. Toxicities were scored using CTCAE v4.0. Eleven patients (6 women) were enrolled with a median age of 61 years (44-66 yrs), AJCC stage of III (n = 2) or IV (n = 9) and oral cavity (n = 10) and larynx (n = 1) primary tumors. Seven patients received the starting 30 mg dose including 2 patients that withdrew consent after starting treatment, and 2 that experienced hypersensitivity reactions due to docetaxel and were taken off-study. There were 2 dose-limiting toxicity (DLT) events of grade 3 diarrhea and mucositis at the initial 30 mg dose. Four patients receive the de-escalated 20 mg dose. There were 2 DLT’s (grade 3 mucositis). There were no grade 4 or 5 events. The most common toxicity was diarrhea occurring in 9 of 11 patients (grade 3 in 2 patients), and mucositis occurring in 8 of 11 patients (grade 3 in 4 patients). The combination of afatinib with both PORT and docetaxel for mucosal SCCHN was shown to be difficult to tolerate with a high rate of grade 3 toxicity, mostly mucositis, in this cohort of patients requiring postoperative chemoradiation to the oral cavity. Afatinib may be better tolerated with PORT alone and this is currently being tested in a prospective phase 1 trial in an intermediate-risk cohort. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Boehringer Ingelheim Pharmaceuticals, Inc.

Efficacy of Transarterial Chemoembolisation with or without Antiviral Therapy for Patients with Hepatocellular Carcinoma after Radical Hepatectomy.

Objective This study aimed at assessing the effects of transcatheter arterial chemoembolisation (TACE) and antiviral therapy on improving the prognosis of patients with hepatocellular carcinoma (HCC) after radical hepatectomy. Methods This study reviewed the data of 120 patients with HCC who received either radical hepatectomy alone (control group), radical hepatectomy with postoperative TACE (TACE group) or radical hepatectomy with combined postoperative TACE, and antiviral therapy (combined group) from January 2000 to May 2015. To reduce the impact of the possible biases on the conclusion of this study to the minimum, the cases with similar demographic and clinicopathological characteristics were collected and 40 cases were assigned into each group. Recurrence, disease-free survival (DFS), and overall survival (OS) rates were compared. Results Median follow-up period was 54.26 ± 22.65 months with a range of 17–110 months. Recurrence after radical surgery was observed for 39 (97.5%) patients in the TACE group, 32 (80%) in the combined group, and 40 (100%) in the control group with median recurrence duration of 33, 43, and 16.5 months, respectively. Postoperative TACE with or without antiviral therapy significantly prolonged the DFS rate compared with radical hepatectomy alone (P = 0.000). TACE combined with antiviral therapy significantly extended the DFS rate compared with TACE alone (P = 0.008). Postoperative TACE with or without antiviral therapy also significantly prolonged the OS rate compared with radical hepatectomy alone (P = 0.000). In addition, antiviral therapy combined with TACE significantly extended the 5-year OS rate of patients compared with individual TACE and radical hepatectomy (67.5% versus 55% and 2.5%; P = 0.032). Conclusion TACE is an appropriate therapy for HCC patients after radical hepatectomy. When combined with antiviral therapy, this treatment may further prolong the recurrence time and thus lead to high DFS and OS rates.

Prospective randomization of post-remission therapy comparing autologous peripheral blood stem cell transplantation versus high-dose cytarabine consolidation for acute myelogenous leukemia in first remission

We prospectively compared outcomes of autologous stem cell transplantation (ASCT) versus high-dose cytarabine (HiDAC) consolidation as post-remission therapy for favorable- and intermediate-risk acute myelogenous leukemia (AML) in first complete remission (CR1). Two-hundred-forty patients under 65years with AML-M1, M2, M4, or M5 subtypes were enrolled. After induction, 153 patients did not undergo randomization, while the remaining 87 who achieved CR1 were prospectively randomized to HiDAC (n=45) or ASCT arm (n=42). In the HiDAC arm, 43 patients completed three cycles of HiDAC, whereas in ASCT arm 22 patients completed two cycles of consolidation consisting of intermediate-dose cytarabine plus mitoxantrone or etoposide followed by ASCT. The three-year disease-free survival (DFS) rate was 41% in HiDAC and 55% in ASCT arm (p=0.25). Three-year overall survival (OS) rates were 77 and 68% (p=0.67). Incidence of relapse was 54 and 41% (p=0.22). There was no significant difference in nonrelapse mortality between two arms (p=0.88). Patients in the ASCT arm tended to have higher DFS rates and lower relapse rates than patients in HiDAC; however, there was no significant improvement in OS in patients with favorable- and intermediate-risk AML in CR1. Patients with AML are not benefited by the intensified chemotherapy represented by ASCT.

Safety Results of a Multi-Institutional Phase 1 Clinical Trial of Afatinib in Combination with Docetaxel and Postoperative Radiation Therapy for High-Risk Squamous Cell Carcinoma of the Head and Neck

Afatinib is an oral, irreversible EGFR/ErbB family receptor inhibitor with clinical activity in recurrent/metastatic SCCHN. Previously, EGFR-inhibition with cetuximab in combination with docetaxel and PORT was shown in RTOG 0234 to be well tolerated with higher rates of disease-free survival compared to historical results with cisplatin and PORT. We therefore aimed to assess the tolerability of afatinib in combination with docetaxel and PORT in a cohort of patients with high-risk pathologic features after definitive surgery. This was an open label, non-randomized, phase I, 3+3 dose-escalation study. Eligible patients had resected stage III-IV SCCHN of the oral cavity, oropharynx, larynx, or hypopharynx with high-risk features of either positive margins (tumor at ink), extracapsular nodal extension, N3 nodal stage, or T4 tumor with bone invasion. Patients received afatinib at an initial dose of 30 mg daily for 1 week prior to PORT and then daily during PORT. Docetaxel 15 mg/m2 was given weekly during PORT. The maximum PORT dose was 66 Gy, 2 Gy/fraction. Toxicities were scored using CTCAE v4.0. Eleven patients (6 women) were enrolled with a median age of 61 years (44-66yrs), AJCC stage of III (n = 2) or IV (n = 9) and oral cavity (n = 10) and larynx (n = 1) primary tumors. Seven patients received the starting 30 mg dose including 2 patients that withdrew consent after starting treatment, and 2 that experienced hypersensitivity reactions due to docetaxel and were taken off-study. There were 2 dose limiting toxicity (DLT) events of grade 3 diarrhea and mucositis at the initial 30 mg dose. Four patients receive the de-escalated 20 mg dose. There were two DLT’s (grade 3 mucositis). There were no grade 4 or 5 events. The most common toxicity was diarrhea occurring in 9 of 11 patients (grade 3 in 2 patients), and mucositis occurring in 8 of 11 patients (grade 3 in 4 patients). The combination of afatinib with both PORT and docetaxel for mucosal SCCHN was shown to be difficult to tolerate with a high rate of grade 3 toxicity, mostly mucositis, in this cohort of patients requiring postoperative chemoradiation to the oral cavity. Afatinib may be better tolerated with PORT-alone and this is currently being tested in a prospective phase I trial in an intermediate-risk cohort.

Value of postmastectomy radiotherapy in locally advanced breast cancer patients treated with neoadjuvant chemotherapy and modified radical mastectomy

Objective To evaluate the value of postmastectomy radiotherapy (PMRT) in locally advanced breast cancer patients treated with neoadjuvant chemotherapy (neoCT) and modified radical mastectomy, and to investigate the possibility of individualized radiotherapy according to the response to neoCT. Methods We analyzed 523 patients with stage ⅢA and ⅢB breast cancer who received neoCT and modified radical mastectomy in our hospital from 1999 to 2013. Of all patients, 404 received PMRT, and 119 did not. The locoregional recurrence (LRR), disease-free survival (DFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method, survival difference analysis and univariate prognostic analysis were performed using the log-rank test, and multivariate prognostic analysis was performed using the Cox regression model. Results Compared with those not treated with PMRT, the patients treated with PMRT had a significantly lower 5-year LRR rate (13.9% vs. 24.8%, P=0.013), a significantly higher DFS rate (64.1% vs. 53.9%, P=0.048), and an insignificantly higher OS rate (83.2% vs. 78.2%, P=0.389). In the patients with ypT3-T4, ypN2-N3, or pathologic stage Ⅲ disease, those treated with PMRT had a significantly reduced 5-year LRR rate (P<0.05) and a significantly increased 5-year OS rate (P<0.05), as compared with those not treated with PMRT. Among the 158 patients with ypN0 disease, the 5-year LRR rate was significantly lower in those treated with PMRT than in those not treated with PMRT (P=0.004). Of 41 patients who achieved a pathologic complete response, 2 patients, who did not receive PMRT, developed LRR. The multivariate prognostic analysis indicated that PMRT was an independent prognostic factor associated with reduced LRR in all patients and ypN0 patients. Conclusions In patients with stage ⅢA and ⅢB breast cancer treated with neoCT and modified radical mastectomy, PMRT can significantly reduce LRR for all patients and can reduce both recurrence and mortality for those with ypT3-T4, ypN2-N3, or pathologic stage Ⅲ disease. There is no sufficient evidence that PMRT can be omitted safely for ypN0 or pCR patients according to their response to neoCT. Key words: Breast neoplasms/chemotherapy; chemotherapy, neoadjuvant; Breast neoplasms/surgery; Surgery, mastectomy; Breast neoplasms/radiotherapy; Prognosis

AQP9-induced cell cycle arrest is associated with RAS activation and improves chemotherapy treatment efficacy in colorectal cancer

Aquaporin-9 (AQP9) expression is associated with arsenic sensitivity in leukemia cells. However, the role of AQP9 in regulating tumor sensitivity to adjuvant chemotherapy in colorectal cancer (CRC) has not been elucidated. In this study, we demonstrated that AQP9 can serve as an independent predictive marker for adjuvant chemotherapy in CRC. Patients with high AQP9 expression had higher rate of disease-free survival (DFS) than those with low AQP9 expression. Upregulation of AQP9 was associated with enhanced chemosensitivity to 5-fluorouracil (5-FU) both in vitro and in vivo. Overexpression of AQP9 resulted in an increased intracellular level of 5-FU in CRC cells, hence leading to a higher percentage of apoptosis after 5-FU treatment. Moreover, AQP9 is positively associated with RAS activation and other downstream signaling molecules in CRC. AQP9 overexpression resulted in p21 upregulation and induced S-phase arrest. Taken together, AQP9 enhances the cytotoxic response to 5-FU in CRC cells by simultaneously inducing S-phase arrest via activation of RAS signaling and facilitating drug uptake. Our results suggest that AQP9 might be a novel predictor for the benefit of 5-FU-based chemotherapy in CRC. The identification of AQP9-induced tumor sensitivity to 5-FU highlights the role of AQP9 in regulating chemosensitivity in CRC.