Preview: Japanese Journal of Clinical Oncology - current issue
Japanese Journal of Clinical Oncology Current Issue
Published: Wed, 25 Jan 2017 00:00:00 GMT
Last Build Date: Wed, 25 Jan 2017 05:44:09 GMT
A Phase II/III randomized controlled trial comparing perioperative versus postoperative chemotherapy with mFOLFOX6 for lower rectal cancer with suspected lateral pelvic node metastasis: Japan Clinical Oncology Group Study JCOG1310 (PRECIOUS study)
A randomized phase II/III trial was started in May 2015 comparing perioperative versus postoperative chemotherapy with modified infusional ﬂuorouracil and folinic acid with oxaliplatin for lower rectal cancer patients with suspected lateral pelvic node metastasis. The standard arm is total mesorectal excision or tumor-specific mesorectal excision with lateral pelvic node dissection (LND) followed by postoperative chemotherapy (modified infusional ﬂuorouracil and folinic acid with oxaliplatin; 12 cycles). The experimental (perioperative chemotherapy) arm is six courses of modified infusional ﬂuorouracil and folinic acid with oxaliplatin before and six courses after total mesorectal excision with lateral pelvic node dissection. The aim of this trial is to confirm the superiority of perioperative chemotherapy. A total of 330 patients will be enrolled over 7 years. The primary endpoint in Phase II part is proportion of R0 resection and that in Phase III part is overall survival. Secondary endpoints are progression-free survival, local progression-free survival, etc. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000017603 [http://www.umin.ac.jp/ctr/index-j.htm].
Respiration-gated fast-rescanning carbon-ion radiotherapy
Phase-controlled rescanning of the carbon-ion beam offers fast and precise dose application with decreased irradiation of normal tissue. However, organ movement with respiration remains a unique challenge. Technological development has enabled the simultaneous application of beam-energy-modulated markerless phase-controlled rescanning with respiration gating, allowing scanning treatment of respiration-mobile tumors with carbon. A total of 10 patients with tumors in the liver or lung were treated in a feasibility study at our facility using this combination. At a median of 10.5 months, follow-up examination including computed tomography/magnetic resonance imaging revealed no grade 2+ acute adverse effects with this new therapy. Two patients with complex disease experienced local recurrence, which may be improved with increased dose delivery. One patient died of unrelated causes. All other patients are alive with good control at the time of writing. Though long-term observation is pending, these are promising initial results for use of the carbon-beam phase-controlled rescanning method in respiration-mobile disease.
Efficacy of reduced dose of pegfilgrastim in Japanese breast cancer patients receiving dose-dense doxorubicin and cyclophosphamide therapy
BackgroundThis retrospective study aimed to evaluate the efficacy of a 3.6-mg dose of pegfilgrastim for primary prophylaxis in Japanese breast cancer patients receiving dose-dense chemotherapy.
MethodsPatients treated with adjuvant or neoadjuvant chemotherapy for early-stage breast cancer at the Tokyo-West Tokushukai Hospital were included in this analysis. Because 6 mg pegfilgrastim has not yet been approved for use in Japan, we compared the outcomes of a dose-dense doxorubicin and cyclophosphamide regimen plus 3.6 mg pegfilgrastim support with a conventional dose epirubicin and cyclophosphamide regimen. The incidence of febrile neutropenia, relative dose intensity, dose delay, dose reduction, regimen change and hospitalization because of neutropenia were assessed.
ResultsFrom November 2013 to March 2016, 97 patients with stage I–III invasive breast cancer were analyzed (dose-dense doxorubicin and cyclophosphamide plus 3.6-mg pegfilgrastim group, n = 41; epirubicin and cyclophosphamide group, n = 56; median ages, 49.0 and 48.5 years, respectively). Febrile neutropenia occurred during the first chemotherapy cycle in 7 of 56 patients (12.5%) in the epirubicin and cyclophosphamide group and 0 of 41 patients in the dose-dense doxorubicin and cyclophosphamide group (P = 0.02). The average relative dose intensities were 97.9% and 96.8%, respectively (P = 0.28), with corresponding dose delay rates of 4.9% (2/41) and 16.1% (9/56), respectively (P = 0.11) and dose reduction rates of 0% (0/41) and 7.1% (4/56), respectively (P = 0.16).
ConclusionsOur results indicate the efficacy of a 3.6-mg pegfilgrastim dose for the primary prevention of febrile neutropenia in dose-dense doxorubicin- and cyclophosphamide-treated Japanese breast cancer patients.
Are hospital cancer caseloads related to the validity of staging data reported? A lesson from National Cancer Registry in Taiwan
ObjectiveData from the National Taiwan Cancer Registry have been widely used since 2002 to assess quality of health, but its quality of coding in cancer staging data has not been discussed. This study assessed the agreement rate for staging by site visit at medical institutes.
MethodsIn this retrospective chart review study, 392 cancer patients in year 2013 were randomly selected from 14 hospitals; the senior cancer registrar reviewers had compared each original chart with data from the Taiwan Cancer Registry to assess agreement rate for staging. The hospitals were classified into two groups on the basis of the number of cancer patients. The kappa (κ) statistic method and multiple regression analysis were used to compare among the medical institutes and qualified cancer registrars.
ResultsThe agreement rate was high in pharynx, esophageal, rectal, breast and prostate cancers, and low in ovarian and other cancers for clinical and pathological staging. After adjustment for the experience of the qualified cancer registrar, low-caseload hospitals had a significantly lower clinical staging agreement rate than that of high-caseload hospitals. After controlling the hospital cancer caseloads the cancer registrar background becomes one of significant factor. That is long duration between a basic license to an advanced license exceeded 5 years, having lower agreement rate.
ConclusionsThe reliability of staging data in the Taiwan Cancer Registry is affected not only by the cancer type but also by the number of patients treated in hospital. Moreover, the experience of cancer registrar strongly influences agreement rate, especially in clinical staging.
The role of pulmonary resection in tumors metastatic from esophageal carcinoma
ObjectiveThe purposes of this study were to determine the role of surgical treatment and to identify factors affecting survival of patients undergoing resection of pulmonary metastatic tumors from esophageal carcinoma.
MethodsWe reviewed 33 patients who had undergone resection of pulmonary metastatic tumors from esophageal carcinoma after definitive treatment.
ResultsThe operative morbidity rate was only 5%, no patients died within 30 days after resection, and complete resection was achieved in 30 patients. The overall 1-, 3- and 5-year survival rates after pulmonary metastasectomy were 79.4, 47.8 and 43.0%, respectively, and the median survival time was 17.9 months. The factors found on univariate analysis to affect survival significantly were disease-free interval <16 months and nodal involvement of the primary tumor. The most frequent pattern of initial recurrence after pulmonary resection was distant metastasis (70%).
ConclusionsWe demonstrated the safety and effectiveness of surgical resection for selected patients with pulmonary metastatic tumors from esophageal carcinoma. However, with a high recurrence rate in patients with negative prognostic factors, adjuvant systemic chemotherapy after pulmonary resection should be considered.
Adjuvant therapy after radical surgery for stage IB–IIB cervical adenocarcinoma with risk factors
ObjectivePatients with adeno/adenosquamous carcinoma may have a poorer prognosis than patients with squamous cell carcinoma. Radiotherapy and concurrent chemoradiotherapy are used as adjuvant therapies for cervical cancer, regardless of the histological subtype. The aim of this study was to investigate the prognostic outcome of adjuvant therapy for patients with adeno/adenosquamous carcinoma with pathological risk factors.
MethodsThe medical records of 135 patients with stage IB–IIB cervical cancer with squamous cell carcinoma or adeno/adenosquamous carcinoma who underwent primary surgery followed by adjuvant therapy were retrospectively reviewed. Patients with a pathologically confirmed bulky tumor (≥4 cm), nodal metastasis and/or parametrium invasion were included in the study.
ResultsThe median follow-up period was 48 (1–132) months. Of the 135 patients, 90 with squamous cell carcinoma and 23 with adeno/adenosquamous carcinoma were treated with adjuvant radiotherapy and concurrent chemoradiotherapy (SCC-RT/CCRT and AC-RT/CCRT groups), and 22 with adeno/adenosquamous carcinoma were treated with adjuvant systemic chemotherapy (AC-CT group). There were no significant differences in clinicopathological factors between the SCC-RT/CCRT and AC-RT/CCRT groups and between the AC-RT/CCRT and AC-CT groups. Progression-free survival was significantly shorter in the AC-RT/CCRT group compared to the SCC-RT/CCRT group (P = 0.002). Adeno/adenosquamous carcinoma histology and multiple lymph node metastasis were independent prognostic factors for shorter progression-free survival in patients treated with adjuvant radiotherapy and concurrent chemoradiotherapy. Progression-free survival was also significantly shorter in the AC-RT/CCRT group compared to the AC-CT group (P = 0.026).
ConclusionsAdjuvant radiotherapy and concurrent chemoradiotherapy may be less effective for patients with adeno/adenosquamous carcinoma than for those with squamous cell carcinoma. Adjuvant systemic chemotherapy may be beneficial for adeno/adenosquamous carcinoma and further studies are warranted.
A single-arm study evaluating bevacizumab, cisplatin, and paclitaxel followed by single-agent bevacizumab in Japanese patients with advanced cervical cancer
BackgroundAdding bevacizumab to chemotherapy for recurrent, persistent or metastatic cervical cancer significantly improved overall survival (primary endpoint), progression-free survival and overall response rate in the randomized Phase III GOG-0240 trial. However, data for bevacizumab-containing therapy are scarce in Japanese patients with advanced cervical cancer.
MethodsThe primary objective of the single-arm multicenter Phase II JO29569 study was to evaluate the tolerability of paclitaxel (135 mg/m2 over 24 h or 175 mg/m2 over 3 h), cisplatin (50 mg/m2) and bevacizumab (15 mg/kg), administered every 3 weeks until disease progression or unacceptable toxicity in Japanese patients with stage IVB, persistent or recurrent cervical cancer.
ResultsThe seven treated patients received a median of nine (range 7–12) bevacizumab cycles and six (range 4–12) chemotherapy cycles. None of the predefined adverse events occurred during the tolerability evaluation period. The most common all-grade adverse events were alopecia, hypertension, decreased appetite, nausea and peripheral sensory neuropathy. There were no cases of fistula. The most common grade ≥3 adverse events were hypertension, neutrophil count decreased and neutropenia. Only one patient experienced febrile neutropenia. The overall response rate was 86% (95% confidence interval, 42–100%), including a complete response in one patient. At data cutoff, disease had progressed in one patient; bevacizumab therapy was ongoing in the remaining six.
ConclusionsAccording to the specified primary objective, a regimen of cisplatin, paclitaxel and bevacizumab was tolerable in Japanese patients and demonstrated encouraging activity in this small single-arm study. Further study is warranted to confirm the safety and effectiveness of bevacizumab in Japanese patients with cervical cancer.
Quality of life and functional status of terminally ill head and neck cancer patients: a nation-wide, prospective observational study at tertiary cancer centers in Japan
BackgroundLittle is known about quality of life and functional status of patients with terminally ill head and neck cancers.
MethodsWe conducted a multicenter, prospective, observational study to examine quality of life and functional status in terminally ill head and neck cancer patients.
ResultsOf the 100 patients meeting inclusion criteria, 72 were observed until death. There was no significant difference in the quality of life score between baseline and Week 3. Forty patients (54.9%) could speak and 22 patients (30.5%) could have oral intake upon study entry. Fifty-three patients (74.6%) received enteral nutrition. Twenty-six patients (36.6%) required dressing changes for fungating tumors. The route of nutritional intake (nasogastric tube vs. percutaneous gastric tube) might be predictive for the duration of hospital stay (64 vs. 21 days, P = 0.0372).
ConclusionThere was no significant relationship between quality of life and functional status seen in this study. Feeding tube type could have the most impact on quality of life.
Safety, efficacy and pharmacokinetics of humanized anti-CD52 monoclonal antibody alemtuzumab in Japanese patients with relapsed or refractory B-cell chronic lymphocytic leukemia
ObjectiveTo evaluate the safety, efficacy and pharmacokinetics of alemtuzumab in Japanese patients, we conducted a phase I study in patients with relapsed or refractory B-cell chronic lymphocytic leukemia.
MethodsSix patients received alemtuzumab by intravenous infusion every other day three times a week for 12 weeks. The dose was gradually escalated on daily basis (3, 10 and then 30 mg) until the patient tolerated. The primary objective was to evaluate the safety of alemtuzumab in Japanese patients and the secondary objectives were to evaluate the overall response rate and the pharmacokinetics.
ResultsThe major treatment-emergent adverse events were anemia, neutropenia (6/6 patients each) and thrombocytopenia (5/6 patients) in hematologic adverse events, and nausea, vomiting, decreased appetite, cytomegalovirus test positive and pyrexia (4/6 patients) in non-hematologic adverse events. As serious adverse events, cytomegalovirus infection, pulmonary tuberculosis and diffuse large B-cell lymphoma were reported in 1/6 patient each. The overall response rate was 33% (95% confidence interval: 4–78) (1/6 patient each achieved complete response and partial response, respectively) and 3/6 patients had stable disease and 1/6 patient had progressive disease. The median time to response was 2.9 months. After last intravenous dosing (Week 12) of alemtuzumab 30 mg every other day three times a week, Cmax, tmax, AUC0−τ and t1/2 were higher and CL and Vss were lower than the values observed after the first dose.
ConclusionsThe efficacy, safety and pharmacokinetics results observed with alemtuzumab in Japanese patients were generally similar to those reported in overseas clinical studies. Alemtuzumab at 30 mg by intravenous infusion every other day three times a week for 12 weeks should be safe and effective similarly in Japanese B-cell chronic lymphocytic leukemia patients.
Clinical trial registration no.NCT00923182.
Clinical outcomes of stereotactic ablative radiotherapy in patients with pulmonary metastasis
BackgroundsIn addition to its curative use for early stage lung cancer, stereotactic ablative radiotherapy is also indicated for pulmonary metastatic disease. Aims of this study were to retrospectively analyze treatment outcomes and to find prognostic factors for survivals.
MethodsTreatment outcomes and toxicities of 85 cases of SABR in 72 patients were retrospectively reviewed from September 2012 to April 2015. Prognostic factors were analyzed using Cox proportional hazards regression.
ResultsThe local failure-free survival rate at 2 years was 98%. Of the case, 1-year and 2-year progression-free survival rates were 62% and 48%, and overall survival rates were 90% and 72%, respectively. Multivariate analyses demonstrated that controlled primary cancer (P = 0.01), absence of extra-pulmonary metastatic disease (P < 0.01) and disease-free interval longer than 1 year (P < 0.01) favorably affected progression-free survival. Furthermore, the absence of extra-pulmonary metastatic disease (P < 0.01) increased overall survival as well. Grade 1 or 2 radiation pneumonitis was found in 37 cases, and Grade 1 chest wall pain was found in 1 case.
ConclusionsStereotactic ablative radiotherapy demonstrated good local control with tolerable adverse effects for pulmonary metastasis. The presence or absence of extra-pulmonary metastasis was found to be prognostic factor of mortality after stereotactic ablative radiotherapy treatment.
Long-term single-institute experience with trimodal bladder-preserving therapy with proton beam therapy for muscle-invasive bladder cancer
ObjectiveWe retrospectively elucidated the oncological outcomes, prognostic factors and toxicities of proton beam therapy in trimodal bladder-preserving therapy for muscle-invasive bladder cancer at our institution.
MethodsFrom 1990 to 2015, 70 patients with cT2–3N0M0 muscle-invasive bladder cancer underwent trimodal bladder-preserving therapy consisting of maximal transurethral resection of the bladder tumor, small pelvis photon irradiation, intra-arterial chemotherapy and proton beam therapy. The overall survival rate, progression-free survival rate, time to progression, predictive factors for progression and toxicities were analyzed. Progression was defined as when muscle-invasive recurrence, distant metastasis or upper urinary tract recurrence was observed.
ResultsThe patients’ median age was 65 (range 36–85) years. The median follow-up period was 3.4 (range 0.6–19.5) years. The 5-year cumulative overall survival rate, progression-free survival rate and time to progression rate were 82%, 77%, and 82%, respectively. In univariate and multivariate analyses, tumor multiplicity and tumor size (≥5 cm) were significant and independent factors associated with progression (hazard ratio 3.5, 95% confidence interval 1.1–12; hazard ratio 5.0, 95% confidence interval 1.3–17; P < 0.05 for all). As for toxicity, 26 (18%) patients had grade 3–4 acute hematologic toxicities and 2 (3%) patients had grade 3 late genitourinary toxicity. No patient had to discontinue the treatment due to acute toxicity.
ConclusionsOur bladder-preserving therapy with proton beam therapy was well tolerated and achieved a favorable mortality rate. Tumor multiplicity and tumor size were important risk factors for progression. Our findings indicate that this therapy can be an effective treatment option for selected muscle-invasive bladder cancer patients.
Postoperative early ultrasensitive prostate-specific antigen identifies patients at risk for biochemical recurrence in margin positive prostate cancers: a single-center study
ObjectiveTo identify predictors for biochemical recurrence among patients with positive surgical margins (RM1) after radical prostatectomy and to examine the effect of ultrasensitive prostate-specific antigen measured early after prostatectomy on biochemical recurrence.
MethodsWe identified 705 patients with prostate cancer who were treated with radical prostatectomy without preoperative hormonal therapy at our institution between 2000 and 2014. The patients with RM1 who had a postoperative prostate-specific antigen <0.2 ng/ml without lymph node metastasis were evaluated for biochemical recurrence–free survival. Survival rates were calculated using the Kaplan–Meier method. The Cox regression model was used for multivariate analysis. The prediction of biochemical recurrence was assessed using area under the curve of the receiver operating characteristic.
ResultsAmong the 705 patients, 190 (27%) had RM1. Biochemical recurrence was evaluated in 164 patients, excluding 26 patients who underwent adjuvant therapy with or without lymph node metastasis. With a median follow-up of 55 months, the biochemical recurrence–free survival rate of the entire RM1 cohort was 78% at 2 years and 64% at 4 years. The multivariate analysis revealed that postoperative early ultrasensitive prostate-specific antigen >0.02 ng/ml was the significant risk factor for biochemical recurrence (hazard ratio 13.10). Meanwhile, the patients with postoperative early ultrasensitive prostate-specific antigen <0.01 ng/ml had a significantly lower risk for biochemical recurrence (hazard ratio 0.12). Area under the curve for the postoperative early ultrasensitive prostate-specific antigen value to predict biochemical recurrence was 0.789.
ConclusionsThe ultrasensitive prostate-specific antigen value measured early after prostatectomy was the potent predictor of biochemical recurrence among the patients with RM1.
Classification of adult diffuse gliomas by molecular markers—a short review with historical footnote
AbstractClassification of gliomas, first established by Cushing and Bailey in early 20th century, has been based on histological features that were associated with clinical behavior of the tumor fairly well. However, inter-observer variation in the diagnosis and heterogeneous clinical outcome within a single entity have been problematic in some cases. Accumulation of molecular information of gliomas over the past two to three decades gradually elucidated the mechanism of oncogenesis and progression of gliomas at the molecular level, and it now appears to be possible to classify gliomas by the molecular markers, especially in adult diffuse gliomas that constitute ~25–30% of the primary intracranial tumors. Most powerful molecular markers to classify those tumors are those that appear to be involved in the early phases of oncogenesis, including IDH1/2, TP53, TERT, ATRX and 1p/19q co-deletion. Interesting tight negative and positive correlations among those molecular genetic alterations enable clearer definition of entities and better prognosis prediction in adult diffuse gliomas.
Limited resection for early-stage non-small cell lung cancer as function-preserving radical surgery: a review
AbstractSince ‘radical lobectomy’ was reported by Cahan in 1960, the standard surgical care for lung cancer has been lobectomy, in which units of the lobe are excised with their specific regional hilar and mediastinal lymphatics. However, pulmonary function-preserving limited resection for lung cancer has gradually become more prevalent in the late 20th century. In 1995, Ginsberg et al. conducted a randomized controlled trial in which limited resection (segmentectomy and wide-wedge resection) and lobectomy for stage I lung cancer were compared and reported that limited resection should not be applied to healthy patients with clinical stage IA lung cancer. The detection of small-sized and early-stage lung cancers has improved with advancement in diagnostic technology. Ground-glass opacity of lung nodules, as recognized on thin-slice computed tomography, has also been widely recognized as being correlated with less-invasive pathological findings of alveolar epithelial cell replacement of cancer cells. The Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group conducted a cohort study of early peripheral lung cancer and investigated the validity thin-slice computed tomography criteria to diagnose non-invasive lung adenocarcinoma for the preoperative prediction of pathological non-invasive cancer. Following this observational study, the on-going JCOG0802/WJOG4607L, JCOG0804/WJOG4507L and JCOG1211 trials were initiated to confirm the validity of limited resection for stage I lung cancer patients stratified according to preoperative thin-slice computed tomography findings; these trials will clarify whether limited resection for lung cancer is not function-preserving but also only curative surgery.