CT-guided radioactive seed implantation for recurrent rectal carcinoma after multiple therapy

The recurrent carcinoma has been difficult to manage after surgery and radiotherapy, extensive resection of locally recurrent rectal cancer is associated with significant morbidity and mortality. Re-irradiation, even in combination with chemotherapy has shown very short survival. We assess the feasibility and efficacy of CT-guided interstitial permanent brachytherapy with ¹²⁵I or ¹⁰³Pd seeds for recurrent rectal cancer after multiple treatments. Fifteen patients with locally recurrent rectal carcinoma received ¹²⁵I or ¹⁰³Pd seed implants under CT guidance. The minimal peripheral dose of seed implants was 110–165 Gy (median 150 Gy). Two weeks after seed implantation, a 50 Gy of stereotactic radiotherapy was given to one patient; four patients received 2–4 cycles of chemotherapy. A median follow-up was 8 months (range 4–50 months). The duration of pain-free survival was 0–50 months (median 7 months). Local control was maintained for 3–50 months (median 7 months). The 1- and 2-year local controls were 16.2 and 8.1%, respectively. Eleven patients died: two (18.2%) of local recurrence, seven (63.6%) of local recurrence and metastases, and two (18.2%) of metastases. Four patients (26.7%) survived the median survival was 9 months. The 1- and 2-year actuarial overall survival rates were 42.9% and 10.7%, respectively. One patient (7.6%) experienced a grade 4 toxic event; there was no associated neuropathy. CT-guided radioactive seed implantation is feasible and safe as a salvage or palliative pain relief treatment for patients with recurrent rectal cancers after surgery and radiotherapy.     

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.     

Salvage therapy with single agent bevacizumab for recurrent glioblastoma

A retrospective evaluation of single agent bevacizumab in adults with recurrent glioblastoma (GBM) with an objective of determining progression free survival (PFS). There is no standard therapy for recurrent GBM after failure of alkylator-based chemotherapy. A total of 50 adults, ages 36–70 years (median 64), with recurrent GBM were treated. All patients had previously been treated with surgery, concurrent radiotherapy and temozolomide, post-radiotherapy temozolomide and in 34 patients, one salvage regimen (PCV: 21, cyclophosphamide: 13). A total of 13 patients underwent repeat surgery. Patients were treated at first or second recurrence with bevacizumab, once every 2 weeks, defined as a single cycle. Neurological evaluation was performed every 2 weeks and neuroradiographic assessment following the initial 2 cycles of bevacizumab and subsequently after every 4 cycles of bevacizumab. A total of 468 cycles of bevacizumab (median 2 cycles; range 1–30) was administered. Bevacizumab-related toxicity included fatigue (16 patients; 4 grade 3), leukopenia (9; 1 grade 3), anemia (5; 0 grade 3), hypertension (7; 1 grade 3), deep vein thrombosis (4; 1 grade 3) and wound dehiscence (2; 1 grade 3). 21 patients (42%) demonstrated a partial radiographic response and 29 (58%) progressive disease following 1–2 cycles of bevacizumab. Time to tumor progression ranged from 0.5 to 15 months (median: 1.0 months). Survival ranged from 2 to 17 months (median: 8.5 months). 6-month and 12-month PFS were 42% and 22% respectively. Single agent bevacizumab demonstrated efficacy and acceptable toxicity in this cohort of adults with recurrent alkylator-refractory GBM.     

Efficacy of high-dose chemotherapy or standard salvage therapy in patients with recurrent medulloblastoma

The efficacy of high-dose chemotherapy (HDC) or standard salvage therapy was evaluated in patients with recurrent medulloblastoma (MBL) using retrospective chart review of all patients with recurrent MBL treated at Duke University Medical Center between 1995 and 2005 and who had undergone HDC with or without radiotherapy (RT) or standard salvage therapy after relapse. A total of 30 patients were diagnosed with recurrent MBL after standard RT alone or chemotherapy with RT. Nineteen patients (7 who received no RT before recurrence [group A] and 12 who received definitive RT before recurrence [group B]) underwent surgery and/or induction chemotherapy followed by HDC plus autologous stem-cell rescue. Eleven patients (group C) underwent standard salvage therapy. Six of seven group A patients also received standard RT just before or after recovery from HDC, and 5 of 12 group B patients received adjuvant palliative focal RT post-HDC. At a median follow-up of 28 months, three of seven patients in group A are alive and disease-free at >or=34, >or=110, and >or=116 months, respectively, post-HDC. All patients in groups B and C have died of tumor, at a median of 35 months and 26 months from HDC and standard salvage therapy, respectively. HDC or standard salvage therapy was ineffective in our patients with recurrent MBL who had received standard RT before recurrence. The favorable impact of HDC on disease control in the two long-term survivors cannot be clearly established due to the cofounding effect of definitive RT postrecurrence.     

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.     

Salvage reirradiation for recurrent glioblastoma with radiosurgery: radiographic response and improved survival

Purpose To determine the radiographic and clinical efficacy of stereotactic single dose radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) as salvage therapy for glioblastoma (GBM) at recurrence. Methods Thirty-six patients with pathologically proven recurrent GBM were treated with salvage reirradiation by either SRS or FSRT between March of 2001 and August of 2006. Thirty-one patients had an initial diagnosis of GBM. Five patients had a malignant transformation. All patients had received radiotherapy with a dose of 50–60 Gy, a median 13.6 months prior to reirradiation (range: 0.8–119 months). At the time of recurrence, 26 patients were treated with SRS with a median dose of 18 Gy (range: 12–20 Gy). FSRT was performed in ten patients with a dose of 36 Gy in six fractions, twice weekly. Follow-up included MRI and clinical examination every 2 months. Results Median survival time after SRS was 8.5 months, compared to 7.4 months after FSRT (P = 0.81). Of 26 patients treated with SRS, radiographic tumor response or stable disease was observed in eight (35%) patients and tumor progression was seen in 18 (65%) patients. Of 10 patients treated by FSRT, radiographic tumor response or stable disease was observed in four (40%) patients and tumor progression was observed in four (40%) patients (two lost to follow-up). Patients who responded to treatment had statistically improved survival compared to non-responders, with median survival of 15.8 vs. 7.3 months (P < 0.05). Conclusion Salvage reirradiation with SRS or FSRT for recurrent GBM results in radiographic response in a proportion of patients. Survival was significantly improved among patients who either responded or had stable disease after salvage reirradiation, compared to non-responders. Further study is warranted to investigate the method and time of reirradiation for recurrent GBM.     

Chemotherapy trials in recurrent primary intracranial germ cell tumors

Summary Gonadal germ cell tumors respond favorably to chemotherapy either at diagnosis or when they recur. Histologically similar tumors may arise in the CNS usually in the pineal or suprasellar regions. Although radiation therapy may produce a 5 year disease-free survival in excess of 60% in localized pure germinoma, gern cell tumors of other histology tend to recur. We have conducted 14 chemotherapy trials in 8 patients with recurrent CNS germ cell tumors using 3 different single agent and 2 multi-agent chemotherapy regimens. The histologic diagnoses of the patients were germinoma (4), endodermal sinus tumor (2), embryonal carcinoma (1), and mixed tumor — germinoma plus choriocarcinoma (1). There were 7 males and 1 female with a median age of 13 years. The primary tumor arose in the pineal region in 6 and was multicentric in 2. Seven patients had local recurrences and one developed an initial recurrence in the spinal canal. Three patients had CNS metastases at relapse and 2 had systemic metastases. Objective responses were documented in 7 of 14 trials (50%). Responses were observed with cyclophosphamide (80 mg/kg) in 3 of 4 patients for 2⁺, 3, and 5 mos, cisplatin (120 mg/m²) in 1 of 2 patients for 2⁺ mos, and the VAB 6 protocol (vinblastine, bleomycin, cyclophosphamide, actinomycin-d, cisplatin) in 3 of 5 patients for 5, 8, and 18 mos. The median duration of response was 5 mos. (2¹-18). High doses of single chemotherapy agents such as cyclophosphamide and cisplatin as well the VAB6 regimen have definite activity in recurrent CNS germ cell tumors, especially germinoma. Good palliation may be achieved with chemotherapy alone with acceptable morbidity. Adjuvant chemotherapy should be considered in patients with newly diagnosed primary intracranial germ cell tumors whose tumors are considered unlikely to be permanently controlled with radiation alone.     

Hydroxyurea for recurrent surgery and radiation refractory high-grade meningioma

Hydroxyurea (HU), an orally administered chemotherapy, has become the de facto standard chemotherapeutic agent in patients with surgically and radiation refractory meningiomas based on a limited literature. A retrospective case series of 35 patients with recurrent WHO Grade 2 (n = 22) or 3 (n = 13) meningioma treated with HU following progression after surgery and radiotherapy was collated with primary study objectives of overall response rate, median and progression free survival (PFS) at 6-months. Thirty-five patients (25 women; 10 men: median age 63 years, range 34–86) with recurrent high-grade meningioma were treated with HU (1,000 mg/m² orally divided twice per day; one cycle operationally defined as 4 weeks of daily HU). Patients had progressed radiographically after prior therapy with surgery (35/35) and radiotherapy (35/35: external beam radiotherapy 35/35; stereotactic radiotherapy 35/35). No patient received prior chemotherapy or targeted therapy before instituting HU. Patients received 0.5–7 cycles (median 2.0) of HU with modest toxicity (28.5% all grades and 8.5% grade 3+ anemia or fatigue). There were no radiographic responses, 43% of patients had stable disease and 57% manifested progressive disease at first evaluation. The overall PFS was 3.0% at 6 months (median PFS 2.0 months; 95% CI 1.6–2.4). The majority of patients (80%) following progression on HU were subsequently treated on an investigational trial. In this retrospective series, HU though well tolerated and convenient appeared to have very limited activity, raise questions of what constitutes effective salvage therapy and indicates an unmet need for alternative treatments for recurrent high-grade meningiomas.     

Stereotactic radiosurgery for pilocytic astrocytomas part 2: outcomes in pediatric patients

To assess outcomes after stereotactic radiosurgery (SRS) for newly diagnosed or recurrent pilocytic astrocytomas in pediatric patients. Fifty patients (28 male and 22 females) with juvenile pilocytic astrocytomas (JPA) underwent Gamma knife SRS between 1987 and 2006. The median patient age was 10.5 years (range, 4.2–17.9 years). Three patients had failed prior fractionated radiation therapy (RT) and two had failed RT and chemotherapy. The median radiosurgery target volume was 2.1 cc (range, 0.17–14.4 cc) and the median margin dose was 14.5 Gy (range, 11–22.5 Gy). At a median follow-up of 55.5 months (range 6.0–190 months), one patient died and 49 were alive. The progression free survival after SRS (including tumor growth and cyst enlargement) for the entire series was 91.7, 82.8 and 70.8% at 1, 3 and 5 years, respectively. Stereotactic radiosurgery for pediatric pilocytic astrocytomas should be considered when resection is not feasible, or if there is an early recurrence. The best response was observed in small volume residual solid tumors.     

Long term outcomes in patients with intracranial germinomas: a single institution experience of irradiation with or without chemotherapy

Complete remission can be achieved soon after irradiation in patients with intracranial germinoma. This study aimed to analyze the follow-up outcome of intracranial germinoma patients. About 39 intracranial germinoma patients (29 males and 10 females; average age, 15 years; range, 7–27 years) treated at Kyoto University Hospital from 1978 to 2004 were included in the study group. Six patients had multifocal disease at initial diagnosis, and 10 had human chorionic gonadotropin (HCG)-producing tumors. Thirteen patients were treated with craniospinal axis irradiation, 6 with whole-brain irradiation, 17 with whole-ventricle irradiation, and 3 with local field irradiation. Since 1997, 15 patients were treated with reduced–dose whole-ventricle irradiation (median, 23.4 Gy; range, 20.4–27 Gy) followed by a local boost (median, 40.8 Gy; range, 36–54 Gy) combined with chemotherapy. The median follow-up was 94 months (18 months to 25 years). The 5- and 10-year overall survival (OS) rates of the entire group were 97 and 90%, respectively. The 5- and 10-year progression-free survival (PFS) rates of the entire group were 91 and 87%, respectively. The 8-year OS and PFS in 15 patients treated by whole-ventricle irradiation combined with chemotherapy were 100% and 92%, respectively. Four patients had recurrences within a median period of 59.5 months (51–85 months). All relapses occurred outside the radiation fields. Tumor site, tumor size, HCG production, multifocal disease and radiation dose to the primary site or whole ventricle did not significantly affect PFS. All initial recurrences of intracranial germinoma occurred at the distant site out of the radiation field. Our data suggested that reduced doses to the whole ventricle, combined with chemotherapy, should be sufficiently effective in patients with intracranial germinoma.     

Radiation therapy for intracranial germinoma: results of the German cooperative prospective trials MAKEI 83/86/89.

PURPOSE: A multicenter prospective trial was conducted (Maligue Keimzelltümoren [MAKEI] 83/86/89) to assess outcome in intracranial germinoma after treatment with radiotherapy alone at reduced doses. PATIENTS AND METHODS: Between 1983 and 1993, 60 patients with histologically (n = 58) or cytologically (n = 2) confirmed germinoma were enrolled onto the study. Patients received radiotherapy alone (craniospinal axis/local boost). In the MAKEI 83/86 study (involving 11 patients), the dose to the craniospinal axis was 36 Gy and the dose to the tumor region was 14 Gy. In the MAKEI 89 study (involving 49 patients), doses were 30 and 15 Gy, respectively. RESULTS: Median patient age was 13 years (range, 6 to 31 years). Complete remission was achieved in all patients. The estimated (Kaplan-Meier) 5-year relapse-free survival rate was 91.0% +/- 3.9% at a mean follow-up of 59.5 months (range, 3 to 180 months); the estimated overall survival rate was 93.7% +/- 3.6%. Relapse occurred in five patients 10 to 33 months (mean, 18.4 months) after diagnosis (one patient developed a spinal canal metastasis and underwent salvage radiotherapy and chemotherapy; four patients had metastases outside the CNS and underwent salvage chemotherapy alone). Four patients died: one died from disease, two died from therapy-related complications, and one committed suicide. Acute complications with long-lasting sequelae were tumor or surgery related (three cases of blindness, six of reduced vision, two of hemiparesis). Psychosocial development was normal in the majority of patients. CONCLUSION: Radiotherapy directed toward the craniospinal axis or tumor site alone at decreased dose levels is effective. To reduce the risk of late side effects, further attempts to decrease total doses are justified. In cases of recurrent disease, chemotherapy administered outside the CNS is the treatment of choice.     

Hydroxyurea for recurrent surgery and radiation refractory meningioma: a retrospective case series

Hydroxyurea (HU), an orally administered chemotherapy, has become the de facto standard therapeutic agent in patients with surgically and radiation refractory meningiomas based on a limited literature. A retrospective case series of 60 patients with recurrent WHO grade 1 meningioma treated with HU following progression after surgery and radiotherapy was conducted with primary study objective progression free survival (PFS) at 6- and 12-months. Sixty patients (45 women; 15 men: median age 61.5 years, range 26–88) with recurrent meningioma were treated with HU (1000 mg/m²/day orally divided twice per day; one cycle operationally defined as 4-weeks of daily HU). All patients had progressed radiographically after prior therapy with surgery (60/60) and radiotherapy (external beam radiotherapy 60/60; stereotactic radiotherapy 53/60). No patient received prior chemotherapy or targeted therapy before instituting HU. Patients received 1-12 cycles (median 2.0) of HU with modest toxicity (10% grade 3 + anemia or fatigue). There were no radiographic responses, 35% of patients had stable disease and 65% manifested progressive disease. Duration of stable disease ranged from 3 to 12 months (median 4.0 months). The overall PFS was 10% (median PFS 2.0 months). The majority of patients (80%) following progression on HU were subsequently treated on an investigational trial. In this retrospective case series, HU though generally well tolerated and convenient, appeared to have very limited activity which raises questions of what constitutes effective salvage therapy and indicates an unmet need for alternative treatments for recurrent meningiomas.     

Salvage gamma knife stereotactic radiosurgery followed by bevacizumab for recurrent glioblastoma multiforme: a case–control study

We evaluated the efficacy and safety of gamma knife stereotactic radiosurgery (GKSR) followed by bevacizumab combined with chemotherapy in 11 patients with recurrent glioblastoma multiforme who experienced tumor progression despite aggressive initial multi-modality treatment. Our experience included eight male and three female patients. The median patient age at GKSR was 62 years (range 46–72 years). At the time of GKSR, seven patients had a first recurrence and four had two or more recurrences. The median interval from the initial diagnosis until GKSR was 17 months (range 5–34.5 months). The median tumor volume was 13.6 cm³ (range 1.2–45.1 cm³) and the median margin dose of GKSR was 16 Gy (range 13–18 Gy). Following GKSR, bevacizumab was administrated with irinotecan in nine patients and with temozolomide in one patient. One patient was treated with bevacizumab monotherapy. The treatment outcomes were compared to 44 case-matched controls who underwent GKSR without additional bevacizumab. At a median of 13.7 months (range 4.6–28.3 months) after radiosurgery, tumor progression was evident in seven patients. The median progression-free survival (PFS) was 15 months (95% confidential interval (CI), 6.5–23.3 months). Six-month and 1-year PFS rates were 73 and 55%, respectively. The median overall survival (OS) from GKSR was 18 months (95% CI, 10.1–25.7 months) and 1-year OS rate was 73%. One patient (9%) experienced grade III toxicity and one patient (9%) had major adverse radiation effects. Compared with patients who did not receive bevacizumab, the patients who received bevacizumab had significantly prolonged PFS (15 months vs. 7 months, P = 0.035) and OS (18 months vs. 12 months, P = 0.005), and were less likely to develop an adverse radiation effect (9 vs. 46%, P = 0.037). The combination of salvage GKSR followed by bevacizumab added potential benefit and little additional risk in a small group of patients with progressive glioblastoma. Further experience is needed to define the efficacy and long-term toxicity with this strategy.     

含美罗华联合方案治疗复发耐药B细胞性非霍奇金淋巴瘤

Objective： The prognosis of relapsed or refractory B-cell lymphoma is poor, with a short-term survival after conventional second-line chemotherapy, Rituximab, a chimeric anti-CD20 antigen, in combination with CHOP or CHOP-like chemotherapy may improve both disease free survival （DFS） and overall survival （OS） of naive patients, but its role in the second-line therapy for relapsed non-Hodgkin＇s Lymphoma （NHL） remains to be defined, This study aimed to evaluate the efficacy of rituximab-containing salvage regimens for relapsed or refractory NHL, and observe the toxicities. Methods： The clinical data of 54 patients, who were with relapsed or refractory NHL and treated in the Cancer Center of Sun Yat-sen University, were analyzed retrospectively, Of the 54 patients, 29 were man, 25 were women, with a median age of 52.5 years old （range 18 to 75）; 50 patients （92.6%） scored 0-1 for the ECOG performance status; for second-line international prognostic index （slPI）, 21 （38.9%） scored 0-1,30 （55.6%） scored 2 to 3, and 3 （5.6%） scored 4-5; 40 cases were diffuse large B-cell lymphoma （DLBCL）, accounting for 74.1% of all subtypes, Rituximab was administered intravenously at a dose of 375 mg/m^2 at the day before each chemotherapy cycle, The second or third-line salvage regimens included EPOCH, CHOP, DHAP, DICE, IVAC, IMVP-16 and FND, Results： Of the 54 patients, 49 received retuximab-containing salvage regimens, The objective response rate of the 45 evaluable cases was 68,8%, with a complete remission （CR） rate of 37.7%; 3 patients achieved CR after radiotherapy following rituximab-based regimens and 3 achieved CR after autologous hematopoietic stem cell transplantation, The most frequent adverse events were leucopenia, nausea and alopecia. The addition of rituximab to chemotherapy only elevated the occurrence of mild infusion-related reactions, such as chills, fever and pruritus. The median follow-up time was 18 months （range 2-86 months）; 5 patients were lost, 24 were dead （23 died of lymphoma, and 1 died of severe hepatitis）, the other patients remained alive. The median survival time was 32 months （range 2-86 months, 95% confidential interval 16-48 months）. The 1-, 2- and 3-year OS rates were 70.6%, 53,6% and 41,5%, respectively, The median TTP was 6 months （range 0-52 months）, The median PFS was 10 months （range 0-47 months, 95% CI 0-26 months）, The 1- and 2-year PFS were 49,3% and 41,3%. Conclusion： Rituximab-containing salvage regimens are effective and well tolerated therapy for patients with relapsed or refractory B-cell NHL, even those were extensively treated.     

Bevacizumab for glioblastoma refractory to vascular endothelial growth factor receptor inhibitors

Glioblastoma (GBM) is a highly vascular tumor dependent on angiogenesis through the vascular endothelial growth factor (VEGF) signaling cascade. Inhibition of VEGF signaling is an important therapeutic strategy. We report our experience with bevacizumab (BEV), a VEGF targeting antibody, following failure of a VEGF receptor targeting tyrosine kinase inhibitor (TKI). We retrospectively identified patients treated on clinical trials with VEGFR–TKIs for recurrent GBM followed by BEV at next recurrence. Survival was estimated by the Kaplan–Meier method. Fourteen patients were identified (six women; median age 57). All received VEGFR–TKIs (sunitinib 11, cediranib 2, sorafenib 1) then BEV at next recurrence. There were no radiographic responses to VEGFR–TKIs; best response was stable disease in 50% (7/14). Patients received BEV alone (21%, 3/14) or in combination with chemotherapy (79%, 11/14). On BEV, 29% (4/14) had a partial response, and 36% (5/14) stabilized. Of evaluable patients, 42% (5/12) had neurological improvement and 56% (5/9) reduced corticosteroid requirement. Median survival on BEV was 7.8 months (95% CI 4.0–15.8), median progression-free survival (PFS) was 4.0 months (95% CI 1.6–10.5), and the 6-month PFS rate was 29% (95% CI 9–52). Our radiographic and survival outcomes with BEV following progression after VEGFR–TKIs are similar to data from studies of BEV as initial salvage therapy, although our sample size was small. Prior exposure to VEGFR–TKIs may not preclude response to BEV, but sensitivity to BEV may be lower following more robust VEGFR inhibition.     

Benefit of re-operation and salvage therapies for recurrent glioblastoma multiforme: results from a single institution

The optimal management of recurrent glioblastoma (GBM) has yet to be determined. We aim to assess the benefits of re-operation and salvage therapies (chemotherapy and/or re-irradiation) for recurrent GBM and to identify prognostic factors associated with better survival. All patients who underwent surgery for GBM between January 2005 and December 2012 followed by adjuvant radiotherapy, and who developed GBM recurrence on imaging were included in this retrospective study. Univariate and multivariate analysis was performed using Cox models in order to identify factors associated with overall survival (OS). One hundred and eighty patients treated to a dose of 60 Gy were diagnosed with recurrent GBM. At a median follow-up time of 6.2 months, the median survival (MS) from time of recurrence was 6.6 months. Sixty-nine patients underwent repeat surgery for recurrence based on imaging. To establish the benefits of repeat surgery and salvage therapies, 68 patients who underwent repeat surgery were matched to patients who did not based on extent of initial resection and presence of subventricular zone involvement at recurrence. MS for patients who underwent re-operation was 9.6 months, compared to 5.3 months for patients who did not have repeat surgery (p?<?0.0001). Multivariate analysis in the matched pairs confirmed that repeat surgery with the addition of other salvage treatment can significantly affect patient outcome (HR 0.53). Re-operation with additional salvage therapies for recurrent GBM provides survival prolongation at the time of progression.     

Chimioradiothérapie de rattrapage à visée curative de rechutes pelviennes isolées de cancers du col utérin

PurposeEvaluation of the results of salvage radiation therapy with curative intent in the treatment of recurrent cervical carcinoma.Patients and methodsFourteen patients with a recurrence of a cervical cancer were treated in our department between 1982 and 2009. Five patients had a pelvic relapse, four a vaginal relapse and five a pelvic lymph node relapse. Four patients had first a surgical resection of the relapse, which was incomplete in two patients. All patients had pelvic radiotherapy with a median dose of 55 Gy in conventional fractionation. Concurrent chemotherapy was administered to 12 patients. A vaginal brachytherapy with a median dose of 20 Gy was performed in addition in 3 patients. The median follow-up was 39 months.ResultsSafety of radiation therapy was correct with 29% of grade 3 acute or intestinal toxicity. Tumor control was observed in 10 patients (71%). Four patients presented a locoregional tumor progression. At the time of analysis, three patients had died from their cancer. From the date of relapse, the rate of overall survival at 2 and 5 year was respectively 84% and 74%. Three patients (21%) had severe late effects.ConclusionIn our experience, chemoradiotherapy can achieve a high rate of remission in patients with isolated pelvic recurrence of cervical cancer. This treatment is feasible only if the patient had not received radiation therapy before or if the relapse is out of the previously irradiated volume.     

Spinal cord ependymomas in adults: analysis of 15 cases

This retrospective analysis was performed to examine the outcome of patients with spinal cord ependymomas treated with surgery and postoperative radiation therapy between 1982 and 1998. There were 10 male and 5 female patients, ranging from 16 to 74 years of age with a median age of 38 years. Surgery was gross total resection in 2 patients, subtotal resection in 10, biopsy in 3. All patients received radiation therapy with a total dose of 40-56 Gy. The 5 and 10 year overall survival rates were 83.3 and 83.3%, respectively. Twelve patients are still alive at a median follow-up period of 70 months. Of the 15 patients, 6 developed recurrent disease on follow-up. The median time to recurrence was 45 months (range: 24-80 months). Local failure within the initial irradiated volume occurred in 3 out of 6 patients who received less than 45 Gy and 2 out of 8 patients treated with more than 45 Gy. Four out of the six failures were salvaged with additional treatment. Re-irradiation was used as a part of salvage or sole treatment in 3 cases. The patient who was salvaged with radiation therapy only died of disease progression 41 months following recurrence and the other two who received a combination of surgery, radiotherapy or chemotherapy were still alive 57 and 30 months following relapse. The present study shows that surgery and post-operative radiation treatment for spinal ependymoma patients resulted in high survival rates. Patients with residual disease after surgery should be treated with radiation therapy with a dose of more than 45 Gy. Re-irradiation may be the treatment of choice for recurrent patients having less than complete resection or no surgery.     

Patterns of survival in patients with Hodgkin's disease: Long follow up in a single centre

BACKGROUND:: Prolonged remission can now be induced in the majority of patientswith Hodgkin's disease with chemotherapy and/or irradiation.However, there is a significant proportion of patients in whomthis approach fails, either at presentation or subsequently.Survival is the definitive endpoint to assess treatment efficacy.In this study, the survival patterns of a large group of consecutivepatients treated in a single institution are presented. RESULTS:: The overall median survival was 18.3 years. Clinical remission(complete remission plus good partial remission) was inducedin 443 (85%); the median survival of patients in remission hasnot been reached. Fifty-eight patients achieved responses lessthan clinical remission with initial therapy (partial response)or had progressive disease, the median survival of this groupbeing 1.4 years. With further therapy, remission was subsequentlyinduced in 10; 5 are still alive, 5 have died between 1.9 yearsand 14.3 years. Twenty patients died before completion of therapy.Recurrence has been documented in 147 of the patients in remission(following initial therapy) over a median follow up period of13 years (minimum 5 years). One hundred forty-three of thesepatients were retreated following recurrence (105 chemotherapy,28 radiotherapy, 6 combined modality treatment and 4 surgery).Second remission was induced in 109/143 (76%). There was a trendtowards better second remission induction in patients whosefirst remission was longer than 1 year (p = 0.06). The medianduration of second remission was inferior to first remissionduration (p < 0.001). There was no correlation between durationof first remission and survival following recurrence (p = 0.8)or with duration of second remission (p = 0.54). There was nosignificant difference in duration of second remission betweenpatients who were initially treated with radiotherapy or chemotherapy(p = 0.3). The median survival following second remission was12.0 years, being the same for patients with initially localizeddisease (stages I and II) treated with radiation alone and forpatients with advanced Hodgkin's disease (stages III and IV)treated with chemotherapy. Survival after recurrence is significantlybetter for patients under 50 years at the time of recurrence(p < 0.001). Second recurrence was documented in 46 patients,third remission being reinduced in 22, the median survival ofthe latter being 5.1 years. CONCLUSION:: These results illustrate the importance of prolonged followup in defining the clinical course of patients with HD and arevital for planning experimental chemotherapy at the time oftreatment failure or recurrence. Hodgkin's disease, salvage therapy, recurrence, relapse, resistant disease, chemotherapy, radiotherapy, survival, remission     

Analysis of surgical salvage after failure of primary therapy in rectal cancer: results from Intergroup Study 0114.

PURPOSE: Intergroup Study 0114 was designed to study the effect of various chemotherapy regimens delivered after potentially curative surgical resection of T3, T4, and/or node-positive rectal cancer. A subset analysis was undertaken to investigate the prevalence and influence of salvage therapy among patients with recurrent disease. PATIENTS AND METHODS: Adjuvant therapy consisted of two cycles of fluorouracil (FU)-based chemotherapy followed by pelvic irradiation with chemotherapy and two more cycles of chemotherapy after radiation therapy. A total of 1,792 patients were entered onto the study and 1,696 were assessable. After a median of 8.9 years of follow-up, 715 patients (42%) had disease recurrence, and an additional 10% died without evidence of disease. Five hundred patients with follow-up information available had a single organ or single site of first recurrence (73.5% of all recurrences). RESULTS: A total of 171 patients (34% of those with a single organ or single site of recurrence) had a potentially curative resection of the metastatic or locally recurrent disease. Single-site first recurrences in the liver, lung, or pelvis occurred in 448 patients (90% of the single-site recurrences), with 159 (35%) of these undergoing surgical resection for attempted cure. Overall survival differed significantly between the resected and nonresected groups (P <.0001), with overall 5-year probabilities of.27 and.06, respectively. Controlling for worst performance status at the time of recurrence does not alter this relationship. Patients who underwent salvage surgery had significantly increased survival (P <.001) for each site. CONCLUSION: Attempted surgical salvage of rectal cancer recurrence is performed commonly in the United States. The chance of a long-term cure with such intervention is approximately 27%.