Salvage radiotherapy in patients with recurrent or refractory primary or secondary central nervous system lymphoma after methotrexate-based chemotherapy

BackgroundTo assess the efficacy of salvage radiation therapy (RT) in patients with recurrent/refractory primary or secondary central nervous system lymphoma (CNSL) after initial methotrexate (MTX)-based chemotherapy and to identify factors associated with treatment outcome.Patients and methodsWe reviewed 36 patients with primary or secondary CNSL who relapsed after MTX therapy and received salvage RT. Primary end points were radiographic response and overall survival (OS).ResultsAfter salvage RT, 18 patients (50%) achieved a complete radiographic response and 6 (17%) achieved a partial response, for an overall response rate of 67% [95% confidence interval (CI) 49% to 81%]. The median OS from start of salvage RT was 11.7 months (range: 0.6–94.7). Patients treated with less than five cycles of MTX before failure had a significantly shorter OS than patients who received five or more cycles (9.2 months versus not reached, P = 0.04). Patients with CNSL limited to brain only had a significantly longer OS than patients with disease in the brain and other central nervous system locations (16.5 versus 4.5 months, P = 0.01).ConclusionSalvage RT is effective for patients with recurrent/refractory primary or secondary CNSL after initial MTX therapy. Having received five or more cycles of MTX before failure and CNSL limited to the brain at relapse are associated with longer OS.     

The role of salvage surgery in patients with recurrent squamous cell carcinoma of the oropharynx

BACKGROUND:

The objective of this study was to comprehensively review overall survival, functional outcomes, and prognostic factors in patients who underwent salvage surgery for locally recurrent squamous cell carcinoma of the oropharynx (SCCOP) after initial radiotherapy.

METHODS:

The authors retrospectively reviewed 1681 consecutive patients who completed definitive therapy for primary SCCOP and identified 168 patients with locally recurrent SCCOP who underwent salvage surgery (41 patients), reirradiation or brachytherapy (18 patients), palliative chemotherapy (70 patients), or supportive care (39 patients).

RESULTS:

Twenty‐six of 39 patients (67%) developed a second recurrence after salvage surgery. The 3‐year overall survival rate for patients who underwent salvage surgery or received reirradiation, palliative chemotherapy, or supportive care were 48.7%, 31.6%, 3.7%, and 5.1%, respectively. For patients who underwent salvage surgery, older age (P = .03), the absence of a disease‐free interval (P < .01), and advanced recurrent tumor stage (P = .07) were associated with lower overall survival. Patients with recurrent neck disease (P = .01) and positive surgical margins (P = .04) had higher rates of recurrence after salvage surgery. Postoperative complications occurred in 19 patients (46%), and there were no perioperative deaths. Functionally, 71% of patients demonstrated ≥80% speech intelligibility, 68% were able to tolerate some oral intake, and 87% who required a tracheotomy subsequently were decannulated.

CONCLUSIONS:

Age, disease‐free interval, recurrent tumor stage, recurrent neck disease, and surgical margin status influenced overall survival or recurrence rate after salvage surgery for recurrent SCCOP. Although most patients had good functional outcomes, only a select group of patients with recurrent SCCOP achieved long‐term survival after salvage surgery. Cancer 2009. © 2009 American Cancer Society.     

High-dose chemotherapy with autologous stem-cell support for germ cell tumors: a critical review

High-dose chemotherapy (HDC) with autologous stem-cell support (ASCS) has been investigated in patients with cisplatin-resistant, relapsed, or poor-prognosis germ cell tumor (GCT). Although some of these patients have benefited from this approach, it is unknown when best to administer such therapy. This review categorizes the HDC/ASCS trials into those performed as (1) salvage therapy for second or greater relapse, (2) salvage therapy for first relapse, and (3) first-line therapy. From the trials performed to date, earlier use of HDC/ASCS (first-line or salvage therapy in first relapse) achieved a higher durable remission rate than when used later as salvage therapy in second or greater relapse (approximately 50% v 15%, respectively). HDC/ASCS is not beneficial for relapsed or cisplatin-resistant primary extragonadal GCT patients, but may have a role in testicular GCT who are not "absolutely" cisplatin-resistant. Trial differences regarding the patients selected and the high-dose transplant preparative regimen used have made precise comparative analyses difficult. There has been only one phase III trial and it did not show a survival advantage to the HDC/ASCS arm, although this trial had significant methodological difficulties. In the future, more definitive treatment recommendations may be made upon completion of two ongoing phase III trials comparing HDC/ASCS with standard chemotherapy in the first salvage and front-line settings.     

Identification of Risk Factors in Patients Treated for First Relapse of Hodgkin's Disease

This review focuses on potential risk factors in patients relapsing with Hodgkin's disease after a first chemotherapy/radiation therapy induced complete remission. This patient group usually presents with highly treatment responsive disease and has become one of the target groups for consideration of salvage high dose chemotherapy with stem cell/autologous marrow support (HDC/ABMT). It is currently not clear to which patients in first relapse this treatment should be offered. The knowledge of certain risk factors could be of great help in assessing such patients. A first group of risk factors are those assessable at initial diagnosis: sex, age, histology, Ann Arbor stage, tumour bulk and some laboratory parameters. A second group of risk factors are those present at the time of relapse: time to relapse, extent of disease at relapse, B-symptoms and performance status, extra nodal lesions at relapse or a relapse within an irradiated field. Age below 50 years seems to exert a small influence on outcome but becomes a major problem above that. There is a small number of characteristics such as the time from the end of initial treatment to relapse or B-symptoms at relapse which seem to be the most prominent factors predicting for freedom from second failure (FF2F). Patients who relapse more than one year after finishing primary chemotherapy and who are free of B symptoms at relapse have a quite favourable outcome after salvage treatment. If their disease is not bulky and is confined entirely to a modest number of previously unirradiated lymph node sites, wide field irradiation offers a reasonable chance of disease control. If their recurrence is bulky, extra-nodal or in a previously irradiated site, the patient's prognosis after HDC/ABMT is excellent. Patients who relapse less than one year after primary chemotherapy or with B symptoms at the time of relapse have a less satisfactory outcome after any available salvage treatment. Trials comparing various HDC/ABMT regimens or novel approaches built on standard dose chemotherapy and irradiation are needed to find better treatments for such patients. Such patients with early or symptomatic relapses who cannot be enrolled in prospective comparative trials should be offered HDC/ABMT while we search for better treatments. Larger trials with a prospective analysis of the risk factors are needed for us to be able to decide which treatment will be the optimal choice for our patients.     

Radiotherapy after subtotally resected or recurrent ganglioglioma

Purpose: Gangliogliomas can recur after subtotal resection (STR). The role of postoperative radiation therapy (RT) is undefined. Methods and Materials: Eight consecutive patients with low-grade gangliogliomas (n = 7) or anaplastic gangliogliomas (n = 1) were treated with RT between 1987 and 2004. Median age was 17 years. Five patients received adjuvant RT after STR at a median time of 6 weeks after surgery. Three patients received salvage RT at a median time of 17 months after surgery. The median dose of RT was 54 Gy. Control was defined as no progressive disease on serial imaging. Median follow-up was 8.8 years. Results: Of the 7 patients with low-grade gangliogliomas, 3 were controlled after RT and 4 recurred locally. Recurrences were controlled with further surgery (n = 2), chemotherapy (n = 1), or re-irradiation (n = 1) (median follow-up, 9 years after salvage therapy). Patients who received adjuvant RT after STR of their low-grade gangliogliomas had an overall local control rate of 75%. All 3 patients who were treated with salvage RT had recurrences in the treated area alone (n = 2) or in the treated area with leptomeningeal spread (n = 1). The patient with an anaplastic ganglioglioma was treated with adjuvant RT, and had recurrence in the radiation field after 4 months, then died 1 month later. Conclusions: Adjuvant RT may be indicated to treat select patients with subtotally resected gangliogliomas. Salvage RT for recurrence is probably less effective for long-term control; however, patients who recur may still be candidates for effective salvage therapies in the absence of malignant transformation.     

Impact of Radiation Therapy After High Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation in Patients With Relapsed/Refractory Lymphomas: A Single Center Experience

IntroductionAfter high dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT), in patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), involved field radiation therapy (RT) for consolidation and residual/progressive disease (PD) eradication is a common practice.Materials and methodsRetrospective single-institution cohort analysis to evaluate the impact of early RT after HDC auto-SCT.ResultsBetween 1996 and October 2019, 153 patients (43 DLBCL, 110 HL) underwent RT after HDC auto-SCT. Males 95 (62%), females 58 (38%), median age 24 years. Indications for RT was consolidation 65%: residual disease eradication 16%: and PD eradication 19%. For DLBCL, the median overall survival (OS) for the above indications was not reached (NR):NR:2 months and the KM 5-year OS was 72.6%:64.3%:12.5% respectively (P ≤ .000). Pair-wise analysis showed that consolidation versus residual disease eradication had no difference (P = .88) but both were superior to PD disease eradication (P ≤ 000 and P = .005 respectively). For HL, indication for RT was, 54%:23%:24% respectively. The median OS was NR:NR:28.8 months and KM 5-year OS was 82.3%:78%:30% respectively (P ≤ .000). Pair-wise analysis showed that consolidation versus residual disease eradication had no difference (P = .98) but both were superior to the PD eradication group (P ≤ 000). RT was well tolerated with no significant long-term toxicity.ConclusionPost HDC auto-SCT RT was well tolerated. DLBCL and HL patients with residual disease treated with the RT had similar long-term survival as those who received RT for consolidation. RT failed to improve the poor survival in patients with post-HDC auto-SCT PD.     

挽救性放疗在局部晚期胃癌根治术后区域淋巴结复发中的作用

目的：评估局部晚期胃癌根治术后挽救性放射治疗在局部区域淋巴结复发中的作用。方法：回顾性分析2005年-2011年26例胃癌术后区域淋巴结复发后行局部放射治疗作为挽救治疗的胃癌患者。排除有腹膜种植转移及远处转移的病例。18个病人进行了放疗,其中部分做了化疗。其他8个仅行化疗未进行放射治疗。三维适形放疗中位剂量56Gy（46~60Gy）。结果：中位随访20个月（4~57个月）。在确诊区域淋巴结复发后中位总生存（ OS ）和无病生存期（ PFS）分别是29个月和12个月。多因素分析显示放射治疗（P＝0.007）和无疾病进展时间（P＝0.030）对于总生存来说是具有显著统计学意义的因子。接受放射治疗者中位总生存期36个月,未行放射治疗者为16个月。此外,进行了放射治疗（ P﹤0.001）做为挽救性治疗后达完全缓解以及体力状态评分与PFS具有明显的相关性。大多数患者接受放射治疗后胃肠道反应比较轻微。结论：挽救性放射治疗联合系统化疗可作为局部晚期胃癌区域淋巴结复发有效的治疗手段。     

Late recurrence and salvage therapy of CNS germinomas

Central nervous system (CNS) germinoma is a curable tumor and its recurrence rate after initial therapy may be approximately 10% or higher. This study elucidates the time-course of recurrence and results of salvage therapy. Twenty-five patients with recurrent germinoma treated at Hokkaido University Hospital were retrospectively reviewed. The median age at initial treatment was 12 years (range: 8–37). All patients had been tumor-free for at least 6 months after the initial treatment. The median follow-up period was 134 months (range: 44–338). The median age at first recurrence was 18 years and the median time to the first recurrence was 50 months. Among the patients, 9 (36%) had the first recurrence at 60 months or later. The latest recurrence in a patient occurred 230 months after the initial treatment. The results of salvage therapy were estimated in all 25 patients. Seventeen patients (68%) were salvaged and were tumor-free at the final observation. The remaining 8 patients died of disease. At first recurrence, 11 patients were treated using radiation therapy with or without surgery and 7 out of the 11 patients died due to the recurrent tumor. On the other hand, 13 patients who received salvage chemotherapy and radiotherapy were tumor-free at the last follow-up. In conclusion, late recurrence is not a rare event in patients with CNS germinoma. To identify a true cure rate of this disease, a 10-year or longer observation period may be required. As a salvage therapy, platinum-based chemotherapy followed by wide-field low-dose radiation therapy appears to be effective.     

Salvage high-dose chemotherapy for children with extragonadal germ-cell tumours

We reviewed the European Group for Blood and Marrow Transplantation (EBMT) experience with salvage high-dose chemotherapy (HDC) in paediatric patients with extragonadal germ-cell tumour (GCT). A total of 23 children with extragonadal GCT, median age 12 years (range 1-20), were treated with salvage HDC with haematopoietic progenitor cell support. The GCT primary location was intracranial site in nine cases, sacrococcyx in eight, retroperitoneum in four, and mediastinum in two. In all, 22 patients had a nongerminomatous GCT and one germinoma. Nine patients received HDC in first- and 14 in second- or third-relapse situation. No toxic deaths occurred. Overall, 16 of 23 patients (70%) achieved a complete remission. With a median follow-up of 66 months (range 31-173 months), 10 (43%) are continuously disease-free. Of six patients who had a disease recurrence after HDC, one achieved a disease-free status with surgical resection followed by chemotherapy and radiotherapy. In total, 11 patients (48%) are currently disease-free. Eight of 14 patients (57%) with extracranial primary and three of nine patients (33%) with intracranial primary GCT are currently disease-free. HDC induced impressive long-term remissions as salvage treatment in children with extragonadal extracranial GCTs. Salvage HDC should be investigated in prospective trials in these patients.     

Intensity-modulated radiotherapy with concurrent chemotherapy for previously irradiated, recurrent head and neck cancer

PURPOSE: Primary treatment fails in >70% of locally advanced head and neck cancer patients. Salvage therapy has a 30-40% response rate, but few long-term survivors. Intensity-modulated radiotherapy (IMRT) has recently emerged as a new modality for salvage therapy. This retrospective study evaluated our experience using every-other-week IMRT with concurrent chemotherapy. METHODS AND MATERIALS: Between 2001 and 2006, 41 patients underwent IMRT as repeat RT with concurrent chemotherapy. All but 6 patients received 60 Gy at 2 Gy/fraction. RT was delivered on an alternating week schedule. RESULTS: With a median follow-up time of 14 months, the overall response rate was 75.6%, with a complete response and partial response rate of 58.5% and 17.1%, respectively. The Kaplan-Meier estimate of overall survival, disease-free survival, and progression-free survival at 24 months was 48.7%, 48.1%, and 38%, respectively. Patients who underwent surgery as a part of their salvage therapy had a mean estimated survival of 30.9 months compared with 22.8 months for patients who received only chemoradiotherapy (p = 0.126). Grade 3 or 4 acute toxicities occurred in 31.7% of patients, but all had resolved within 2 months of therapy completion. No deaths occurred during treatment, except for 1 patient, who died shortly after discontinuing treatment early because of previously undiagnosed metastatic disease; 6 patients had long-term complications. CONCLUSIONS: Concurrent chemotherapy with repeat radiotherapy with IMRT given every other week appears to be both well tolerated and feasible in patients treated with previous radiotherapy for recurrent head and neck cancer. IMRT represents a reasonable modality for reducing treatment-related toxicities in a repeat RT setting.     

Combined salvage therapies for recurrent glioblastoma multiforme: evaluation of an interdisciplinary treatment algorithm

Glioblastoma multiforme patients presenting with recurrence following multimodality therapy have limited palliative treatment options when the major modalities of therapy including surgery, radiochemotherapy and adjuvant chemotherapy have been exhausted. The authors introduce a clinical and radiological indication-solving algorithm and provide outcome rates of a glioblastoma recurrence cohort. Sixty six consecutive adult patients with recurrent glioblastoma who underwent a combined scheme of salvage treatments consisting of reoperation, high dose rate (HDR) brachytherapy and chemotherapy were included in this prospective study and were compared to a historical control group of 24 recurrent glioblastoma patients who have been treated with intensive temozolomide chemotherapy as the only treatment modality. Median follow-up was 32 months (range 28–36 months). Median survival was 9 months for the entire cohort after salvage treatment and can be translated into a 3-month improvement in survival compared to the control group of patients with glioblastoma recurrence treated with temozolomide alone (P = 0.043). Toxicity and adverse events of reoperation, HDR brachytherapy combined with chemotherapy were quite favourable compared to intensive temomozolomide chemotherapy as the only treatment. Our experience suggests that a combined salvage treatment plan appears to be both feasible and effective and can be considered in selected patients affected by recurrent high grade gliomas. The authors’ clinical and radiological indication-solving algorithm may assist in providing the best possible salvage treatment for this difficult population.     

Details of recurrence sites after definitive radiation therapy for cervical cancer

Objective

This is a retrospective study aimed at clarifying the details of recurrence patterns and sites in patients with cervical cancer treated with definitive radiation therapy (RT).

Methods

Data were analyzed from consecutive patients, admitted to the University of Tokyo Hospital (Tokyo, Japan) between 2001 and 2013, who had received definitive RT, with or without chemotherapy, for International Federation of Gynecology and Obstetrics stages IB–IVA cervical cancer.

Results

One hundred and thirty-seven patients formed the patient cohort. The median follow-up period for surviving patients was 57.0 months. A complete response was achieved in 121 patients (88%). Of these, 36 (30%) developed a cancer recurrence during follow-up. The first sites of recurrence were located in intra-RT fields in nine, outside RT fields in 20, and both in seven patients. In the intra-RT field group, all patients showed a local recurrence, while no one experienced an isolated pelvic lymph node (PLN) recurrence. In the outside RT field group, the most frequent site of recurrence was lung (60%), and three-quarters of patients were free from intra-RT field recurrence until the last follow-up. Of the entire cohort, including 48 PLN-positive patients, only seven patients (5.1%) developed PLN persistence or recurrence, all in the common iliac, internal iliac, and/or obturator nodes, and all with another synchronous relapse.

Conclusion

Local disease was a major type of intra-RT field recurrence, while PLN control was favorable even in initially PLN-positive patients. The predominance of outside RT field recurrence alone highlights issues concerning distant control, including the intensity enhancement of systematic therapy.     

Isolated paraaortic lymph node recurrence after definitive irradiation for cervical carcinoma

PURPOSE: To evaluate the clinical features of isolated paraaortic lymph node (PALN) recurrence after definitive radiotherapy, and analyze the prognostic factors and effect of salvage treatment. METHODS AND MATERIALS: Of a total 876 patients who received pelvic radiotherapy after the diagnosis of primary cervical carcinoma, 26 were found to have isolated PALN recurrence as the first recurrent site, and these patients enrolled in this study. Only those with primary-site carcinoma controlled and who were free of other distant metastases were eligible. Nineteen of the 26 patients accepted salvage therapy. Fourteen patients accepted concurrent chemoradiation (CCRT), 1 accepted radiation to the paraaortic region, and 4 accepted chemotherapy alone. Clinical parameters evaluated included tumor markers (SCC and CEA) and image studies. RESULTS: Seven of the 26 patients were alive and disease-free. All 7 survivors had salvage treatment with radiation to the paraaortic region and concurrent cisplatin-based chemotherapy. None of the patients receiving chemotherapy or radiation alone enjoyed long-term, disease-free survival. The 5-year survival rate for isolated PALN recurrence of the 14 patients who accepted salvage concurrent chemoradiation (CCRT) was 51.2%. The presence of a clinical symptom at the time of PALN recurrence was analyzed. Seven of the 12 asymptomatic patients and none of the 14 symptomatic patients survived without disease after salvage treatment. The SCC levels at recurrence showed a statistically significant relationship to disease-free survival. CONCLUSIONS: An SCC level of < or = 4 ng/ml and a lack of symptoms at the time of recurrence were good prognostic factors in isolated PALN recurrence after primary radiation therapy. In addition to concurrent CCRT, periodical surveillance with tumor markers and imaging studies allowed early detection and salvage of those patients.     

High-dose chemotherapy with autologous stem cell transplantation in adults with recurrent embryonal tumors of the central nervous system

BACKGROUND: Embryonal central nervous system (CNS) tumors (medulloblastoma, cerebral neuroblastoma, pineoblastoma, and primitive neuroectodermal tumors) are rare in adults. Recurrent disease has an extremely poor outcome. The use of high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has demonstrated promising results in children with recurrent disease, but there are only limited data regarding its role in adults. The purpose of the current study was to evaluate adult patients with embryonal CNS tumors who were treated with HDC with ASCT and compare their outcomes with those of patients who received conventional-dose chemotherapy. METHODS: The authors reviewed the medical records of 23 adult patients (age >or= 18 years) who were treated at the Mayo Clinic for recurrent embryonal CNS tumors between 1976 and 2004. The authors compared treatment with HDC with ASCT (10 patients) with an historic control of patients treated with conventional-dose chemotherapy (nitrosourea based, cisplatin based, or both) (13 patients). RESULTS: HDC with ASCT was associated with increased survival (P= .044) and a longer time to disease progression (TTP) (P= .028). The conventional-dose chemotherapy group had a median TTP of 0.58 years and a median survival of 2.00 years. The HDC with ASCT group had a median TTP of 1.25 years and a median survival of 3.47 years. When restricted to patients receiving ASCT after first disease recurrence, the median TTP was 2.5 years and the median survival was 4.16 years. Toxicities were similar in both groups. CONCLUSIONS: Improvements in the median TTP and survival noted with the administration of HDC with ASCT, as well as the acceptable toxicity of this regimen, supports consideration of its use in adults with recurrent embryonal CNS tumors.     

Recurrent cervical cancer

Opinion statement There are limited treatment options for patients with recurrent cervical carcinoma. Because of low response rates and a negligible impact on long-term survival, the use of chemotherapy in patients with unresectable recurrent disease should be considered palliative. Generally, radiation therapy in previously irradiated patients is considered palliative. For patients who develop recurrent disease after definitive surgery who have not received prior radiation therapy, salvage radiation therapy is the treatment of choice. Similarly, patients who have received definitive primary radiation therapy are candidates for surgical resection of their recurrence. However, there are specific criteria for surgical resection. Radical hysterectomy may be an option for the very rare patient with a small (<2 cm) centrally located recurrence in the cervix or vaginal fornices. However, for most patients, pelvic exenteration remains the only therapeutic option that offers the possibility of long-term survival. Patients who are candidates for exenteration are those with central local recurrences that have not extended to the pelvic sidewalls. The introduction of high-dose-rate intraoperative radiation therapy (HDR-IORT) combined with radical surgical resection has widened the scope of patients who may be offered surgery. Patients who in the past may not have been surgical candidates may benefit from radical surgical resection combined with HDRIORT. All patients who are surgically fit and have undergone previous radiation therapy should be considered for surgical resection for centrally located recurrences. Patients whose recurrences extend close to the pelvic sidewalls should be referred to centers where HDR-IORT is available.     

Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors.

PURPOSE: To evaluate the efficacy and toxicity of high-dose chemotherapy (HDC) followed by autologous stem-cell rescue (ASCR) in patients with relapsed or progressive CNS germ cell tumors (GCTs). PATIENTS AND METHODS: Twenty-one patients with CNS GCTs who experienced relapse or progression despite having received initial chemotherapy and/or radiotherapy were treated with thiotepa-based HDC regimens followed by ASCR. RESULTS: Estimated overall survival (OS) and event-free survival (EFS) rates for the entire group 4 years after HDC were 57% +/- 12% and 52% +/- 14%, respectively. Seven of nine (78%) patients with germinoma survived disease-free after HDC with a median survival of 48 months. One patient died as a result of progressive disease (PD) 39 months after HDC, and another died as a result of pulmonary fibrosis unrelated to HDC 78 months after ASCR without assessable disease. However, only four of 12 patients (33%) with nongerminomatous germ cell tumors (NGGCTs) survived without evidence of disease, with a median survival of 35 months. Eight patients with NGGCTs died as a result of PD, with a median survival of 4 months after HDC (range, 2 to 17 months). Patients with germinoma fared better than those with NGGCTs (P =.016 and.014 for OS and EFS, respectively). Patients with complete response to HDC also had significantly better outcome (P <.001 for OS and EFS) compared with patients with only a partial response or stable disease. There were no toxic deaths because of HDC. CONCLUSION: Dose escalation of chemotherapy followed by ASCR is effective therapy for patients with recurrent CNS germinomas and might be effective in patients with recurrent NGGCTs with a low tumor burden.     

Recurrent gestational trophoblastic disease. Experience of the Southeastern Regional Trophoblastic Disease Center

Between 1968 and 1985, 28 patients with recurrent gestational trophoblastic disease (GTD) were treated at the Southeastern Regional Trophoblastic Disease Center. Sixteen patients received primary therapy at this center and had recurrence diagnosed by re-elevation of human chorionic gonadotropin (hCG) levels after three consecutive negative levels: five (2.5%) of 204 patients with nonmetastatic GTD, three (3.7%) of 81 with good prognosis metastatic disease, and eight (13%) of 61 with poor prognosis disease. The remaining 12 patients were referred for therapy after receiving primary therapy elsewhere. All episodes of recurrence were observed within 36 months of remission with 50% and 85% before 3 and 18 months, respectively. Fourteen (56%) of 25 patients who achieved secondary remission developed a second recurrence and five (45%) of 11 surviving a second recurrence developed one or more further episodes of recurrent GTD. Nineteen patients (68%) have sustained remission 18 months following therapy for recurrent GTD. Factors relating to development and survival of recurrent disease include: poor prognosis metastatic disease, inadequate initial staging and therapy, lack of adequate maintenance chemotherapy beyond the first negative hCG level, and prolonged intervals between cycles of chemotherapy. Recent regimens introduced have contributed to an increasing salvage rate: 15 of 18 patients treated since 1978 are without evidence of disease whereas only four of ten treated prior to 1978 are currently in remission (P = 0.03).     

The residual mediastinal mass following radiation therapy for Hodgkin's disease

Thirty-two patients with mediastinal involvement by Hodgkin's disease (HD), treated with an isocentric technique of extended-field radiation therapy (RT) with or without chemotherapy, are described. Twenty-nine patients (91%) had a complete response to therapy and four patients subsequently relapsed, with a median follow-up of 54 months. Five of seven patients not in continuous complete remission were salvaged, with one additional salvage therapy. Ten patients had persistent mediastinal masses at 1 year, following completion of planned therapy; only one of these has had recurrent disease. Of those who achieved complete response, only one patient has had disease recurrence in the mediastinum. We conclude that extended-field RT, using an isocentric technique, provides excellent local disease control in HD; however, persistent mediastinal widening after therapy is frequent, and additional therapy should not be given in the absence of conclusive evidence of disease progression.     

Combined modality therapy for primary CNS lymphoma.

PURPOSE: Primary CNS lymphoma (PCNSL), formerly rare, is being seen with increased frequency among apparently immunocompetent patients. Conventional treatment has consisted of whole-brain radiotherapy (RT) and corticosteroids, with a median survival of 15 to 18 months and a 3% to 4% 5-year survival. Chemotherapy has been useful in the treatment of recurrent PCNSL. In 1985 we began a treatment protocol using chemotherapy and cranial irradiation for the initial therapy of non-AIDS PCNSL. PATIENTS AND METHODS: Thirty-one patients (group A) completed the combined modality regimen. All had placement of an Ommaya reservoir and received pre-RT systemic methotrexate, 1 g/m2, plus six doses of intra-Ommaya methotrexate at 12 mg per dose. A full course of cranial RT (4,000-cGy whole-brain RT plus a 1,440-cGy boost) was followed by two cycles of high-dose cytarabine (ara-C), with each course consisting of two doses of 3 g/m2 ara-C separated by 24 hours and infused over 3 hours. During this period, 16 additional patients (group R) were treated with RT alone, either because patients refused chemotherapy or RT was initiated before our consultation; all would have been eligible to participate in the protocol. Follow-up extended through April 1, 1991. RESULTS: Group A had a significantly prolonged time to recurrence (median, 41 months) compared with group R (median, 10 months; P = .003). Although median survival was doubled from 21.7 months for group R to 42.5 months for group A, this was not statistically significant because of small sample size. More importantly, group R patients received systemic chemotherapy for recurrent PCNSL, which improved survival. CONCLUSION: The addition of chemotherapy to cranial RT for initial treatment of PCNSL significantly improved disease-free survival and contributed to overall survival; all non-AIDS patients with newly diagnosed PCNSL should be considered for combined modality therapy.     

Salvage Radiation Therapy for Intracranial Germinoma Recurring After Primary Chemotherapy

Systemic chemotherapy has been increasingly used in the primary treatment of intracranial germinoma. However, the recurrence rate seems to be very high after treatment with chemotherapy alone. We used radiation to treat 5 patients harboring intracranial germinoma that recurred following primary chemotherapy. They had received systemic chemotherapy (4 with cisplatin plus etoposide and 1 with adriamycin, vincristine, cyclophosphamide, prednisolone, and cisplatin) 7–24 months before referral. All patients were treated with conventional radiotherapy directed to the primary tumor site or the craniospinal axis with a dose to the primary site ranging from 39.6 to 47.0 Gy (mean, 42.6 Gy). Response to radiation of all the recurrent tumors was good and all tumors disappeared on diagnostic imaging below the dose of 24 Gy. All patients are alive without further recurrence at 61–129 months after salvage radiotherapy. Germinomas recurring after primary chemotherapy do not seem to have acquired cross resistance to radiotherapy. They can usually be cured by standard radiation therapy with 40–47 Gy.