Clinical outcome following post-chemotherapy retroperitoneal lymph node dissection in men with intermediate- and poor-risk nonseminomatous germ cell tumour

OBJECTIVE: To evaluate the outcome in patients treated with chemotherapy and retroperitoneal lymph node dissection (RPLND) after an initial diagnosis of International Germ Cell Cancer Collaborative Group (IGCCCG) intermediate- and poor-risk metastatic nonseminomatous testicular germ cell tumour (NSGCT), as the integration of chemotherapy and surgery in managing advanced NSGCT continues to develop. PATIENTS AND METHODS: Between 1989 and 2003, 157 patients initially diagnosed with IGCCCG intermediate- and poor-risk NSGCT had RPLND after chemotherapy at the authors' institution, with a median follow-up of 36 months. Progression-free probability (PFP) and disease-specific survival (DSS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to assess the prognostic significance of risk factors for disease progression after RPLND. RESULTS: In all, 68 (43%) and 89 (57%) patients were assigned as intermediate- and poor-risk, respectively. At the time of RPLND the median residual retroperitoneal mass was 3.0 cm and 29 (19%) men had elevated serum tumour markers (alpha-fetoprotein, human chorionic gonadotrophin, or both). Retroperitoneal residual masses were completely resected in 147 (94%) patients; retroperitoneal histology revealed fibrosis in 73 (47%), teratoma in 63 (40%) and viable GCT in 21 (13%). The 5-year overall DSS and PFP were 81% and 70%, respectively. Patients with poor-risk NSGCT were at no greater risk of disease progression than those with intermediate-risk NSGCT. In a multivariate analysis, residual mass size, incomplete surgical resection and the presence of teratoma and viable germ cell cancer independently predicted disease progression after RPLND. CONCLUSIONS: Patients with advanced NSGCT have long-term freedom from disease progression when chemotherapy is combined with resection of residual masses. Our data suggest that the tumour response to chemotherapy, coupled with complete resection of all residual masses, predicts long-term freedom from disease progression.     

Treating stage I nonseminomatous germ cell tumours with a single cycle of chemotherapy

OBJECTIVE: To estimate the rate of relapse in men with stage I nonseminomatous germ cell tumours (NSGCT) of the testis treated with one cycle of chemotherapy instead of the usual two cycles. PATIENTS AND METHODS: Between 1992 and 1996, 22 men with stage I NSGCT who had normalized tumour markers after orchidectomy and negative findings on computed tomography, and who were at moderate risk of relapse, were treated with one cycle of platinum-containing chemotherapy (bleomycin and etoposide with either cisplatin or carboplatin). RESULTS: At a median follow-up of 10.2 years, none of the patients have relapsed with malignant GCTs. CONCLUSION: The results after one cycle of chemotherapy are no worse than after two cycles. The present study needs to be replicated in a larger cohort of patients to define the relapse risk more accurately. This approach is soon to be tested in a large multicentre trial randomizing patients between one and two cycles.     

Induction chemotherapy with cisplatin and gemcitabine followed by accelerated radiotherapy and concurrent cisplatin in patients with stage IV(A-B) nasopharyngeal carcinoma

BACKGROUND: The purpose of this study was to evaluate the efficacy and toxicity of cisplatin plus gemcitabine as induction chemotherapy in advanced nasopharyngeal carcinoma (NPC). METHODS: Thirty-seven patients with stage IV(A-B) NPC were treated with 3 cycles of cisplatin plus gemcitabine (cisplatin 80 mg/m(2) on day 1; gemcitabine 1250 mg/m(2) on days 1 and 8) 3-weekly as induction chemotherapy, followed by another 3 cycles of concurrent cisplatin (100 mg/m(2) on day 1) 3-weekly with accelerated radiotherapy (RT) at 70 Gy in 2-Gy fractions, 6 daily fractions per week. RESULTS: The overall response rate to induction chemotherapy was > 90%, and side effects other than uncomplicated hematologic toxicities were uncommon. All patients completed RT, with 92% receiving > or = 5 cycles of chemotherapy. At a median follow-up of 2.9 years, the 3-year overall survival (OS) and disease-free survival (DFS) rates were 76% and 63%, respectively. CONCLUSIONS: Cisplatin plus gemcitabine is a well-tolerated, effective, and convenient induction chemotherapy regimen and warrants further studies to confirm its benefit in advanced NPC.     

The role of retroperitoneal lymph node dissection in the management of testicular cancer

Despite continued refinement in terms of technique and the integration of retroperitoneal lymph node dissection (RPLND) in the management of patients with testicular cancer, RPLND remains an essential component in the ultimate cure of these patients. The failure to eradicate all disease in the retroperitoneum exposes patients to the risk of late relapse events with potentially lethal consequences. For patients with low-stage nonseminomatous germ cell tumor (NSGCT), primary RPLND is an important staging tool to define subsequent treatment requirements, simplify the follow-up of patients by obviating the need for routine abdominal imaging, and limit the exposure of patients to the long-term toxicity of chemotherapy. RPLND alone is curative in up to 90% of patients with low-volume retroperitoneal disease. In the post-chemotherapy setting, the inability to reliably exclude the presence of teratoma or viable germ cell cancer in the retroperitoneum mandates that post-chemotherapy RPLND be performed for all NSGCT patients with residual masses. With improvements in surgical technique and perioperative care, RPLND is associated with minimal short- and long-term morbidity in the hands of experienced surgeons at dedicated centers. This article reviews the role of RPLND in the management of patients with NSGCT at all stages and its role in advanced seminoma.     

Comparison of surveillance and retroperitoneal lymph node dissection in Stage I nonseminomatous germ cell tumors

Objectives. To compare retrospectively the treatment results of surveillance and primary retroperitoneal lymph node dissection (RPLND) of patients with clinical Stage I nonseminomatous germ cell tumors of the testis (NSGCT) in two institutions in The Netherlands.Methods. From 1982 to 1994, 90 consecutive patients with clinical Stage I NSGCT were prospectively entered in a surveillance protocol in Amsterdam (group 1). In the same period, 101 patients with clinical Stage I NSGCT underwent primary RPLND in Nijmegen (group 2). Both patient populations were comparable for patient age, presence of vascular invasion, and embryonal cell components in the primary tumor. All patients in group 1 with relapse, except for 2, were treated with cisplatin-based chemotherapy. All patients in group 2 with vital tumor in the RPLND specimen were treated with two adjuvant courses of combined chemotherapy (cisplatin, etoposide, and bleomycin).Results. In group 1, at a median follow-up of 7.7 years, 23 patients (26%) had relapse. The median time to relapse was 12 months. Relapses were located retroperitoneally (n = 18, 78%), in the lung (n = 3, 13%), scrotally (n = 1, 4%), and combined in the liver, lung, and pleura (n = 1, 4%). After treatment of relapses (chemotherapy in 21 and/or surgery in 11), only 1 patient died of disseminated disease. A disease-free survival rate of 98.5% was achieved at the median follow-up. The main toxicities consisted of short-lasting leukopenia, accompanied by infection (13%). Four patients reported cardiovascular and four neuropathy complaints. In group 2, the median follow-up was 6.9 years. In 31 patients (30.7%), vital tumor was found retroperitoneally; after two courses of combined chemotherapy, none of them had a relapse. Seven patients with pathologic Stage I disease (6.4%) had a pulmonary relapse within 1 year after surgery. No retroperitoneal relapses were found. After chemotherapy, 6 patients with relapse were salvaged, and 1 died of disseminated disease. The disease-specific survival rate in group 2 was 98% at the median follow-up. The most frequent surgical complications were lymphocele (n = 3), small bowel obstruction (n = 3), and abdominal pain (n = 3). The antegrade ejaculation rate was 94%.Conclusions. Excellent treatment results in terms of disease-free survival can be achieved in Stage I NSGCT with both surveillance and primary RPLND. Patients with pathologic Stage II disease adjuvantly treated with chemotherapy did not have any relapse and consequently all survived. Most complications after both treatment strategies are reversible. The choice of treatment should be based on balanced information and not on dogmatic principles.     

Cardiac Angiosarcoma Management and Outcomes: 20-Year Single-institution Experience

Purpose

To identify the clinicopathologic characteristics, treatments, and outcomes of a series of patients with primary cardiac angiosarcoma (AS).

Methods

This retrospective case series was set in a tertiary referral center with a multidisciplinary clinic. Consecutive patients with institutionally confirmed pathologic diagnosis of cardiac AS from January 1990 to May 2011 were reviewed. Main outcome measures included patient demographics, tumor characteristics, management strategies, disease response, and survival.

Results

Data from 18 patients (78?% male) were reviewed. Sixteen patients (89?%) had AS originating in the right atrium. At diagnosis, eight patients (44?%) had localized/locally advanced disease and ten patients (56?%) had metastatic disease. Initial treatment strategies included resection (44?%), chemotherapy (39?%), and radiotherapy (11?%). Of the eight patients with localized/locally advanced AS, two underwent macroscopically complete resection with negative microscopic margins, one underwent macroscopically complete resection with positive microscopic margins, one underwent macroscopically incomplete resection, two received chemotherapy followed by surgery and intraoperative radiotherapy, one received chemotherapy alone, and one died before planned radiotherapy. Median follow-up was 12?months. Median overall survival (OS) was 13?months for the entire cohort; median OS was 19.5?months for those presenting with localized/locally advanced AS and 6?months for those with metastatic disease at presentation (p?=?0.08). Patients who underwent primary tumor resection had improved median OS compared with patients whose tumors remained in situ (17 vs. 5?months, p?=?0.01).

Conclusions

Cardiac AS is associated with poor prognosis. Resection of primary tumor should be attempted when feasible, as OS may be improved. Nevertheless, most patients die of disease progression.     

Salvage chemotherapy with methotrexate,etoposide and actinomycin D in men with metastatic nonseminomatous germ cell tumors with a choriocarcinoma component: A preliminary report

The objective of the present study was to assess the use of salvage chemotherapy using methotrexate, etoposide and actinomycin D (MEA) in men with nonseminomatous germ cell tumor (NSGCT) with a choriocarcinoma component. Nine patients were included. They had initially received bleomycin, etoposide and cisplatin, and high‐dose ifosfamide, carboplatin and etoposide as induction chemotherapies. However, they failed to achieve the normalization of β‐human chorionic gonadotropin (β‐HCG). Therefore, MEA therapy (methotrexate: 450 mg/body on day 1, actinomycin D: 0.5 mg/body on days 1–5, etoposide: 100 mg/body on days 1–5) was subsequently administered. After MEA therapy (median: 3 cycles), serum β‐HCG was normalized in five of the nine patients. Of these five, three achieved long‐term disease‐free survival and one died of disease unrelated to NSGCT, whereas the remaining patient developed disease recurrence and died of disease progression. All four patients who failed to achieve the normalization of β‐HCG died of disease progression. Although several severe toxicities greater than grade 3, which were mainly associated with bone marrow suppression, occurred in all patients, there was no treatment‐related death. Considering the current outcomes, MEA regimen could be an attractive option as a salvage chemotherapy for metastatic NSGCT patients with a choriocarcinoma component showing resistance to intensive conventional chemotherapies.     

Postchemotherapy retroperitoneal lymph node dissection in patients presenting with very high HCG levels

PurposeChoriocarcinoma germ cell tumors are rare and usually present with significantly elevated human chorionic gonadotropin (hCG) levels. When curable, it is felt to be largely a result of chemotherapy. We sought to determine the histologic characteristics for those undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) and compare them with metastatic nonseminomatous germ cell tumor (NSGCT) patients with similarly elevated hCG levels.MethodsWe reviewed medical records of men undergoing PC-RPLND between 1988 and 2017 with postorchiectomy, preinduction chemotherapy hCG levels greater than 50,000 mIU/ml. They were stratified by primary tumor histology: Pure choriocarcinoma and mixed NSGCT. Clinical, pathologic, and serologic data were reported and logistic regression was used to assess for predictors of necrosis in the PC-RPLND specimen.ResultsOur cohort consisted of 108 men. The mixed group (n = 91) had a median hCG of 165,177 mIU/ml, a postchemotherapy node size of 4.7 cm, of whom 19.8% also received salvage chemotherapy prior to RPLND. The pure choriocarcinoma group (n = 17) had a median hCG of 170,267 mIU/ml, a node size of 5.1 cm, of whom 17.6% received salvage chemotherapy. 88.2% of patients with choriocarcinoma had necrosis in the PC-RPLND specimen compared with 29.7% of the mixed NSGCT group (P = <0.0001). Controlling for salvage chemotherapy use, prechemotherapy hCG, node size and marker status, choriocarcinoma patients were 20 fold more likely to have necrosis on RPLND specimen (Odds ratio 20.68 [95% confidence interval 5.279–81.114]).ConclusionWhile PC-RPLND is appropriate in patients with residual masses after chemotherapy, patients with pure choriocarcinoma presenting with significantly elevated hCG levels represent a unique patient population where necrosis is found more often than anticipated.     

The absence of spermatogenesis in radical orchiectomy specimen is associated with advanced-stage nonseminomatous testicular cancer

BackgroundTo assess if clinical, pathological, and spermatogenesis factors are associated with clinical staging in patients with testicular germ cell tumors.Patients and methodsWe retrospectively reviewed the pathology reports and slides from 267 men who underwent radical orchiectomy for testicular cancer at our institution during 1998-2019. Histologic slides were reviewed and the presence of mature spermatozoa was documented. Clinical, laboratory and radiographic characteristics were recorded. Logistic regression analyses were used to identify factors associated with advanced disease stage at diagnosis.ResultsOf 267 male patients, 115 (43%) patients had testicular non-seminomatous germ cell tumors (NSGCT) and 152 (57%) seminomatous germ cell tumors (SGCT). Among NSGCT patients, those presenting with metastatic disease had a higher proportion of predominant (>50%) embryonal carcinoma (64% vs. 43%, respectively, P = 0.03), and lymphovascular invasion (45.8% vs. 26.6%, respectively, P = 0.03) than non-metastatic patients. Spermatogenesis was observed in 56/65 (86.2%) and 36/49 (73.5%) of non-metastatic and metastatic NSGCT patients, respectively (P = 0.09). On semen analysis, severe oligospermia (<5 million/ml) was more common in metastatic than in non-metastatic NSGCT (26.5% vs. 8.3%, respectively, P = 0.04). On multivariate analysis, predominant embryonal carcinoma and lack of spermatogenesis in pathological specimens were associated with metastatic disease.ConclusionThe absence of spermatogenesis and a high proportion of embryonal carcinoma was associated with advanced disease in patients with NSGCT. Whether it may also translate as a predictor of oncologic outcome needs further evaluation.     

Inflammatory breast cancer: results of antracycline-based neoadjuvant chemotherapy

Abstract: Twenty-three patients with inflammatory breast cancer treated with a combined modality approach including anthracycline-based induction chemotherapy-surgery-chemotherapy-radiotherapy were reviewed. Twelve patients (52.2%) received FAC (5-fluorouracil, adriamycin, cyclophosphamide) and 11 patients (47.8%) were treated with FEC (5-fluorouracil, epirubicin, cyclophosphamide) induction chemotherapy for three cycles every 3 weeks. Surgery was followed by the initial chemotherapy or second-line chemotherapy for an additional six cycles to complete nine cycles and radiotherapy, respectively. The median overall survival (OS) time was 27 months and the median disease-free survival (DFS) was 13 months. Furthermore, patients treated with FAC induction chemotherapy have been found to have longer median OS and DFS periods compared to patients with FEC induction chemotherapy in both univariate and multivariate analysis. In conclusion, the superiority of doxorubicin-containing chemotherapy over epirubicin-containing chemotherapy should be established in larger randomized studies and more effective chemotherapeutic agents such as taxans are required for better survival rates in inflammatory breast cancer patients.      

Surveillance Study for Clinical Stage I Testicular Seminomas and Nonseminomatous Germ Cell Tumors

Background: Optimal therapy for stage I testicular tumors is still controversial. This study evaluated the efficacy of a surveillance policy for patients with testicular stage I seminomas and nonseminomatous germ cell tumors (NSGCT).
Methods: From 1984 to 1996, 24 patients with stage I semi noma and 20 with stage I NSGCT were fol lowed after radical orchiectomy with tumor markers and imaging studies. All patients were followed for at least 2 years except for those who recurred within 2 years. Recurrent patients were treated with cisplatin-based chemotherapy.
Results: The median follow-up periods for seminoma and NSGCT patients were 41 and 54 months, respectively. Recurrences were detected in 2 seminoma (8.3%) and 10 NSGCT (50%) patients. Eleven of the 1 2 recurrent patients (92%) were detected within 2 years after orchiectomy. The seminoma patients both recurred in the retroperitoneal lymph nodes, while 70% of the NSGCT patients recurred in the lung and/or retroperitoneal lymph nodes. The recurrent seminoma patients were treated with chemotherapy and are alive without disease for 1 7 and 24 months after orchiectomy. One NSGCT patient died of cancer, but the other 9 recurrent NSGCT patients are alive without disease at 25 to 11 3 months after orchiectomy.
Conclusions: Surveillance alone is reliable for monitoring patients with stage I testicular seminoma and NSGCT. The majority of recurrences occurred within 2 years, necessitating intensive follow-up for 3 years. As the lung metastatic rates in NSGCT patients were high, a more accurate assessment for lung metastasis is desirable in these patients.     

Post-chemotherapy robotic retroperitoneal lymph node dissection (RRPLND) in testicular cancer

We report here on the safety and feasibility of using robotic surgery for the excision of residual retroperitoneal lymph node metastasis in patients with non-seminomatous germ cell testicular tumors (NSGCT) post-chemotherapy (PC). Two men (age 20 and 21?years, respectively) with residual PC retroperitoneal disease underwent robotic assisted retroperitoneal lymph node dissection (RRPLND). The primary testicular tumor was on the right testicle in one patient and on the left testicle in the other patient. Both patients had a history of testicular NSGCT and bulky retroperitoneal lymph node metastasis and had received chemotherapy. The technique, feasibility, and safety of the RRPLND procedure are reported. RRPLND was safely accomplished in both patients. A right-side approach was performed in one patient; a left-side approach was utilized in the other patient. In both patients, the field of dissection was an ipsilateral template for lymph node dissection, including excision of the residual mass. No intraoperative or postoperative complications were encountered. Pathology showed mature teratomatous elements in both patients. We demonstrate here the safety and feasibility of performing template RRPLND in patients with PC residual masses. Further reports are needed to compare this procedure to its other approaches, namely, standard open and laparoscopic RPLND.     

Effect of preoperative chemotherapy for bulky N2 non-small-cell lung cancer]

The effect of chemotherapy as the adjuvant therapy to bulky N2 disease (stage IIIA) non-small-cell lung cancer was examined. From January 1992 to December 1996, 464 patients with non-small-cell lung cancer underwent surgery. Seven patients (1.5%) with N2 disease (stage IIIA) received two cycles of preresectional cisplatin and vindesin chemotherapy, followed by standardized surgical resection (Group A). 46 patients (9.9%) had pathological N2 disease (T1-3, M0) after surgery (Group B). In Group A a complete resection was accomplished in two patients (28.6%), and five patients had incomplete resection with a deseased margin, followed thoracic irradiation 60 to 75 Gy. In three patients in Group A the N2 disease was pathologically downstaged to N1 or N0 disease. Overall survival at five years in Group A and in Group B was 48% and 39%, and median survival time was 49 months and 38 months. Although complete resection rate was lower in Group A (28.6%) than in Group B (78.2%), there was no significant difference between five year survival and median survival time in Group A and Group B. These data may be thought to suggest that induction chemotherapy in Group A was effective on occult micrometastatic disease.     

Treatment of a population based sample of men diagnosed with testicular cancer in the United States

ObjectivesTesticular cancer is the most common cancer in men age 25 to 35 years. We examined therapy, compliance with guidelines, and survival in a population based sample of men newly diagnosed with testicular cancer.Materials and MethodsWe analyzed the National Cancer Institute's (NCI) patterns of care data on 702 men diagnosed with testicular cancer in 1999. These studies supplement routine data collection by verifying therapy with the patients' treating physicians. Follow-up for vital status was available through December 31, 2004.ResultsThe majority of the men with seminoma were diagnosed while their cancer was localized and more than 80% of received orchiectomy with radiation. For men with seminoma and nonseminoma germ cell tumors (NSGCT), the percent receiving chemotherapy increased markedly as stage increased. More than 90% of men with regional and distant NSGCT received chemotherapy. Less than 25% of men with localized NSGCT received orchiectomy and retroperitoneal lymph node dissection (RPLND), about 40% had surveillance following an orchiectomy alone, and 30% received orchiectomy and chemotherapy.ConclusionsThe majority of these patients received therapy consistent with guidelines. While there was no significant difference in the use of RPLND in men with localized NSGCT by geographic region, chemotherapy use varied widely. Over 90% of men with localized or regional disease diagnosed in 1999 were alive at the end of 2004. The excellent survival rates point to the need to monitor for late effects of therapy.     

PRETREATMENT FOLLICLE-STIMULATING HORMONE: A PROGNOSTIC SERUM MARKER OF SPERMATOGENESIS STATUS IN PATIENTS TREATED FOR GERM CELL CANCER

Purpose

We evaluate the use of pretreatment follicle-stimulating hormone (FSH) in patients with germ cell tumors as a prognostic serum marker of spermatogenesis after standard treatment. Additionally, Leydig cell function was investigated by estimation of luteinizing hormone (LH) and testosterone (T), and calculation of the T/LH ratio.

Materials and Methods

Serum FSH, LH and T were determined radioimmunologically associated with semen analyses in 20 patients with seminoma (pathological stages IA to IIB) after unilateral orchiectomy before and up to 24 months after infradiaphragmatic radiotherapy. Additionally, hormone analyses were performed in 18 patients with nonseminomatous germ cell tumor (pathological stages IIA to C) before and up to 36 months after standard cisplatin based chemotherapy.

Results

Seminoma patients undergoing radiotherapy were divided into 2 groups consisting of 12 patients with normal pretreatment serum FSH and 8 with elevated FSH reflecting spermatogenesis deficits even before treatment. Six months after irradiation a significant increase in FSH (p <0.01) associated with a decrease in sperm density was observed in both groups and 24 months after radiotherapy patients with initially normal FSH had significantly lower serum FSH (p <0.01) associated with higher sperm density than those with initially elevated FSH (p <0.01), indicating less impairment of Sertoli cell function. Comparable results were observed in chemotherapy treated germ cell tumor patients with initially normal (11) and elevated serum FSH (7), respectively, and 36 months after chemotherapy patients with initially normal FSH had significantly lower FSH concentrations than those with initially elevated FSH (p <0.01). Compensated impairment of Leydig cell function reflected by a subnormal T/LH ratio was evident before chemotherapy in 16.7% of patients increasing up to 41.2% 36 months after therapy. In contrast, 24 months after radiotherapy only 25% of seminoma patients showed a subnormal ratio reflecting less damage to the Leydig cells caused by irradiation.

Conclusions

Pretreatment FSH is a prognostic serum marker of spermatogenesis status of germ cell tumor patients receiving standard radiotherapy or chemotherapy. In contrast to seminoma patients after radiotherapy, impairment of Leydig cell function was evident in germ cell tumor patients after cisplatin based chemotherapy.     

PSA倍增时间对去势抵抗性前列腺癌患者多西他赛化疗后总生存期的影响

目的:探讨化疗前PSA倍增时间(PSADT)对接受多西他赛化疗的转移性去势抵抗性前列腺癌(mCRPC)患者总生存期(OS)的影响。方法:回顾性分析2005年11月～2011年9月接受多西他赛化疗的115例mCRPC患者资料。115例患者均有骨转移,其中16例患者伴有内脏器官转移。115例随访45(2～74)个月,对可能影响化疗疗效的因素进行单因素生存分析,并对其中有统计学意义的指标进行多因素分析。生存函数分析运用Kapian-Meier法,采用Log-rank法进行显著性检验。结果:至随访截止日期,115例中87例死亡,28例生存。接受多西他赛化疗1～16个疗程,平均6个疗程。全组患者中位OS为(17.0±1.9)个月。单因素生存分析显示:化疗前基线PSA值、化疗前PSADT、基线血红蛋白(Hb)浓度、ECOG评分、激素敏感时间及化疗周期数与mCRPC患者多西他赛化疗后OS相关。化疗前PSADT<46.3d和PSADT≥46.3d组中位OS分别为(14.0±2.1)个月和(23.0±2.2)个月(差异有统计学意义,P<0.01)。结论:化疗前PSADT、基线Hb浓度、激素敏感时间及化疗周期数为mCRPC患者多西他赛化疗后OS的独立预后因素。     

Impact of the number of positive lymph nodes on disease-free survival in patients with pathological stage B1 nonseminomatous germ cell tumor

PURPOSE: The prognostic significance of the number of metastatic lymph nodes detected at surgery on survival is well documented for breast and colon cancer, and it has recently been reported in bladder cancer. We tested this hypothesis in patients with pathological stage B1 nonseminomatous germ cell tumor (NSGCT). MATERIAL AND METHODS: This series included 118 patients with pathological stage B1 NSGCT (5 or fewer positive lymph nodes) at primary retroperitoneal lymph node dissection who did not receive adjuvant chemotherapy at a followup of greater than 24 months. RESULTS: Five-year disease-free survival (DFS) was 68% at a median followup of 43 months. Median followup in patients without recurrence was 67.4 months and median time to recurrence was 5.0 months. The mean and median number of positive lymph nodes was 2.0. Five-year DFS for 1 or 2 and 3 to 5 positive lymph nodes was 72% and 59%, respectively (p = 0.0847). Five-year DFS for lymph node density less or greater than 0.05 was 75% and 66%, respectively (p = 0.261). Neither the number of positive lymph nodes (continuous and categorical p = 0.201 and 0.271) or the ratio of the number of positive lymph nodes to the total number resected (continuous and categorical p = 0.415 and 0.998, respectively) predicted recurrence. CONCLUSIONS: Primary retroperitoneal lymph node dissection is curative in patients with pathological stage B1 NSGCT and DFS does not seem to be influenced by the number or the ratio of positive lymph nodes resected. This information may be helpful in limiting adjuvant chemotherapy in patients otherwise cured by surgery.     

Breast Care

Purpose

Chemotherapy-induced amenorrhea is a serious concern for women undergoing cancer therapy. This prospective randomized trial evaluated the use of gonadotropin-releasing hormone (GnRH) analog triptorelin to preserve ovarian function in women treated with chemotherapy for early-stage breast cancer.

Patients and Methods

Premenopausal women age 44 years or younger were randomly assigned to receive either triptorelin or no triptorelin during (neo)adjuvant chemotherapy and were further stratified by age (< 35, 35 to 39, > 39 years), estrogen receptor status, and chemotherapy regimen. Objectives included the resumption of menses and serial monitoring of follicle-stimulating hormone (FSH) and inhibin A and B levels.

Results

Targeted for 124 patients with a planned 5-year follow-up, the trial was stopped for futility after 49 patients were enrolled (median age, 39 years; range, 21 to 43 years); 47 patients were treated according to assigned groups with four cycles of adriamycin plus cyclophosphamide alone or followed by four cycles of paclitaxel or six cycles of fluorouracil, epirubicin, and cyclophosphamide. Menstruation resumed in 19 (90%) of 21 patients in the control group and in 23 (88%) of 26 in the triptorelin group (P= .36). Menses returned after a median of 5.8 months (range, 1 to 19 months) after completion of chemotherapy in the triptorelin versus 5.0 months (range, 0 to 28 months) in the control arm (P= .58). Two patients (age 26 and 35 years at random assignment) in the control group had spontaneous pregnancies with term deliveries. FSH and inhibin B levels correlated with menstrual status.

Conclusion

When stratified for age, estrogen receptor status, and treatment regimen, amenorrhea rates on triptorelin were comparable to those seen in the control group.     

High-dose chemotherapy with peripheral blood stem cell autotransplantation for patients with poor-risk testicular germ cell tumors--pilot study of the Japan Blood Cell Transplantation Study Group

The efficacy and toxicity of a single cycle of high-dose chemotherapy with peripheral blood stem cell autotransplantation (PBSCT) in patients with poor-risk testicular germ cell tumors (GCT) enrolled in the Japan Blood Cell Transplantation Study Group was investigated. Previously untreated poor-risk testicular GCT patients were treated with BEP therapy (cisplatin, etoposide and bleomycin) with or without high-dose chemotherapy (carboplatin, etoposide and ifosphamide) followed by PBSCT. Patients were qualified for a change to high-dose chemotherapy if elevated serum tumor markers (human chorionic gonadotropin-beta, alpha-fetoprotein and lactate dehydrogenase) was observed after 3 cycles of BEP therapy. Eighteen patients were treated with BEP therapy alone and 16 with BEP and high-dose chemotherapy. At the completion of high-dose chemotherapy, all tumor markers had returned to normal in 6 patients. Among them, 1 had only teratoma found at resection and 5 had carcinoma resected. Nine patients who had persistent elevation of any tumor marker were treated with high-dose chemotherapy or another anticancer drug. Thirteen are alive (81%) and 9 (56%) are continuously disease-free at a median follow up of 11 months. The median time from PBSCT to a granulocyte count > 500/microL was 9.5 days and to a platelet count > 50,000/microL was 13 days.     

Retrospective Analysis of Bevacizumab in Combination with Ifosfamide,Carboplatin, and Etoposide in Patients with Second Recurrence of Glioblastoma

Bevacizumab has been reported to be effective for recurrent glioblastoma. In our hospital, ifosfamide, carboplatin, etoposide (ICE) is the second-line chemotherapy for first recurrence of glioblastoma after temozolomide failure. In the present analysis, we retrospectively investigated the feasibility and effectiveness of bevacizumab combined with ICE in patients with glioblastoma at second relapse during ICE treatment. Between 2010 and 2012, tumor progressions were diagnosed in consecutive 8 patients who were treated with ICE for the first recurrence of glioblastoma. These patients were administered 3 cycles of 10 mg/kg bevacizumab every two weeks in combination with ICE treatment. The objective response rate of bevacizumab combination was 75% in Neuro-Oncology Working Group (RANO criteria), including complete response and partial response. Median progression free survival (PFS) and median overall survival (OS) after second relapse were 3.7 months (95% confidence interval [CI], 2.5–18.5 months) and 6.0 months (95% CI, 3.2–19.7 months), respectively. The 6-month PFS rates were 25% (95% CI, 0–55.0%). The median OS after initial diagnosis was 23.3 months (95% CI, 16.2–55.8 months). The grade 2 or 3 hematologic adverse events were identified in 7 of 8 patients, most of which might be due to ICE chemotherapy. The results of our retrospective analysis suggest that combination treatment with bevacizumab and ICE may be safe and beneficial in patients with recurrent glioblastoma.