Sustained Complete Response Research Articles

Radiotherapy for Nasopharyngeal Carcinoma and Combined Capecitabine and Nimotuzumab Treatment for Lung Metastases in a Liver Transplantation Recipient: A Case Experience of Sustained Complete Response

The primary treatment for nasopharyngeal carcinoma (NPC) is external beam radiotherapy. However, until now, there is little experience with the management of NPC occurred after solid organ transplantation. In this report, a 60-year-old man was found to have NPC (T2N1M0; stage III) 3 years after orthotopic liver transplantation treatment for hepatocellular carcinoma. Intensity-modulated radiotherapy (IMRT) was performed for NPC. One month after IMRT, complete response of NPC was achieved. However, multiple lung metastases occurred 18 months after the IMRT with the largest lesion measuring 4.1×5.5 cm and confirmed to be originated from NPC. Combined chemo-/targeted therapy consisted of capecitabine, and nimotuzumab was administered for four cycles. One month after initiation of capecitabine plus nimotuzumab treatment, a near-complete response was achieved for lung metastases. A repeat CT scan 1 year later showed sustained resolution of the lung metastases. The patient is still alive 16 months after the combined chemo-/targeted therapy.

Critical appraisal of the ‘wait and see’ approach in rectal cancer for clinical complete responders after chemoradiation

Some 10-20 per cent of patients with locally advanced rectal cancer achieve a pathological complete response (pCR) at surgery following preoperative chemoradiation (CRT). Some demonstrate a sustained clinical complete response (cCR), defined as absence of clinically detectable residual tumour after CRT, and do not undergo resection. The aim of this review was to evaluate non-operative treatment of rectal cancer after CRT, and the outcome of patients observed without radical surgery. A systematic computerized search identified 30 publications (9 series, 650 patients) evaluating a non-operative approach after CRT. Original data were extracted and tabulated, and study quality evaluated. The primary outcome measure was cCR. Secondary outcome measures included locoregional failure rate, disease-free survival and overall survival. The most recent Habr-Gama series reported a low locoregional failure rate of 4·6 per cent, with 5-year overall and disease-free survival rates of 96 and 72 per cent respectively. These findings were supported by a small prospective Dutch study. However, other retrospective series have described higher recurrence rates. All studies were heterogeneous in staging, inclusion criteria, study design and rigour of follow-up after CRT, which might explain the different outcomes. The definition of cCR was inconsistent, with only partial concordance with pCR. The results suggested that patients who are observed, but subsequently fail to sustain a cCR, may fare worse than those who undergo immediate tumour resection. The rationale of a 'wait and see' policy relies mainly on retrospective observations from a single series. Proof of principle in small low rectal cancers, where clinical assessment is easy, should not be extrapolated uncritically to more advanced cancers where nodal involvement is common. Long-term prospective observational studies with more uniform inclusion criteria are required to evaluate the risk versus benefit.

Long Term Complete Remission in Advanced Gastric Adenocarcinoma With Docetaxel, Oxaliplatin and Capecitabine Combination Regimen

Gastrointestinal tract cancers are highly lethal malignancies with early metastatic dissemination. Chemotherapy is therefore of crucial importance in advanced cancer for obtaining palliation of symptoms and improving survival. However, there is no universal standard chemotherapy regimen for the treatment of gastroesophageal cancer. Also, complete remission is an uncommon outcome in advanced gastroesophageal cancers treated with chemotherapy; and where encountered, the response is not sustained. We present a 65 year-old patient who presented with advanced gastric adenocarcinoma. She had histopathologically proven liver metastases. She was treated with chemotherapy comprising of six cycles of Docetaxel, Oxaliplatin and Capecitabine (DOX). She showed complete remission with disappearance of local as well as liver lesions, and achieved disease free status for 9 months. This is the first known sustained Complete Response in a case of advanced gastric carcinoma with DOX combination regimen.

Phase II Trial of Erlotinib and Docetaxel in Advanced and Refractory Hepatocellular and Biliary Cancers: Hoosier Oncology Group GI06-101

Abstract Background. Patients with advanced hepatocellular (HCC) and biliary tract carcinomas (BTC) have poor prognosis. While the EGFR pathway is overactive in HCC and BTC, single agent anti-EGFR therapies confer modest activity. Preclinical data showed synergistic antiproliferative and proapoptotic effects between anti-EGFR therapies and taxanes. We conducted a phase I study of erlotinib and docetaxel in solid tumors, and noted good tolerability and sustained complete (5 years +) and partial responses in patients with HCC and BTC. This trial evaluated the efficacy of erlotinib with docetaxel in refractory hepatobiliary cancers. Methods. Eligible patients were allowed to have two prior systemic therapies. Docetaxel 30 mg/m2 i.v. was administered on days 1, 8, 15, and erlotinib 150 mg was dosed orally on days 2–7, 9–14, 16–28 of each 28-day cycle. The primary endpoint was 16 weeks progression-free survival (PFS), and secondary endpoints included response, stable disease, and overall survival. Tumor samples were analyzed for KRAS gene mutations and E-cadherin expression by immunohistochemistry (IHC). Patients with BTC and HCC were accrued and assessed in separate strata for the efficacy endpoints, but for the two-stage initial design of the study, combined PFS was considered. A Simon optimal two-stage design tested the hypothesis that the 16-week PFS is ≤ 15% (clinically inactive) versus the alternative of ≥ 30% (warranting further study). Results. Twenty-five patients, 14 with HCC and 11 with BTC, were enrolled. Common toxicities were rash (76%), diarrhea (56%), and fatigue (52%), mostly grade 1 or 2. No objective responses were seen. Seven BTC (64%) and 6 HCC patients (46%) had stable disease as best response, with a median duration of 16.1 weeks (95% CI 3.7–56.3) for BTC, and 17.6 weeks (95% CI 8.1–49.8) for HCC. The 16-week PFS was 64% for BTC (95% CI 29.7–84.5), and 38% for HCC (95% CI 14.1–62.8). Median overall survival was 5.7 and 6.7 months for BTC and HCC patients, respectively. BTC patients with grade ≥ 2 rash had higher median PFS (6.2 vs 2.2 months) and OS (14.2 vs 4.2 months). HCC patients with negative/low E-cadherin expression had higher median PFS (6.7 vs 2.1 months) and OS (14.5 vs 4 months). Conclusion. Erlotinib with docetaxel met the 16-week PFS ≥ 30% endpoint,but overall survival was comparable to that seen with single-agent erlotinib. With the limitation of small numbers of patients, grade ≥ 2 rash (in BTC), and negative/low E-cadherin expression (HCC) were associated with higher PFS and OS.

Discontinuation of imatinib in Japanese patients with chronic myeloid leukemia

It was recently recognized that some chronic myeloid leukemia patients with a complete molecular response could sustain that response after discontinuation of imatinib. To characterize the clinical outcomes and profiles of chronic phase chronic myeloid leukemia patients who could discontinue imatinib, we conducted a nationwide survey in Japan. Among 3,242 imatinib-treated chronic myeloid leukemia patients, we identified 50 who had discontinued imatinib for at least six months; of these we analyzed 43. Molecular recurrence was detected in 19 patients, and a complete molecular response rate was estimated to be 47% following imatinib discontinuation. Based on multivariate regression analysis, imatinib dose intensity and prior interferon-α administration were independently predictive of molecular recurrence within 12 months. The depth of the molecular response should be a factor influencing long-term sustained complete molecular response after discontinuation of imatinib. Additionally, an immunological mechanism modified by interferon-α might control chronic myeloid leukemia stem cells.

New Insights into Therapeutic Targets in Myeloma

Patient outcome in multiple myeloma (MM) has been remarkably improved due to the use of combination therapies including proteasome inhibitors and immunomodulatory drugs, which target the tumor in its BM microenvironment. Ongoing efforts to improve the treatment paradigm even further include using oncogenomics to better characterize molecular pathogenesis and to develop refined patient stratification and personalized medicine in MM; using models of MM in its BM milieu to identify novel targets and to validate next-generation therapeutics directed at these targets; developing immune-based therapies including mAbs, immunotoxins targeting MM cells and cytokines, and novel vaccine strategies; and using functional oncogenomics to inform the design of novel combination therapies. With continued rapid evolution of progress in these areas, MM will be a chronic illness with sustained complete response in a significant number of patients.

New Insights into Therapeutic Targets in Myeloma

Patient outcome in multiple myeloma (MM) has been remarkably improved due to the use of combination therapies including proteasome inhibitors and immunomodulatory drugs, which target the tumor in its BM microenvironment. Ongoing efforts to improve the treatment paradigm even further include using oncogenomics to better characterize molecular pathogenesis and to develop refined patient stratification and personalized medicine in MM; using models of MM in its BM milieu to identify novel targets and to validate next-generation therapeutics directed at these targets; developing immune-based therapies including mAbs, immunotoxins targeting MM cells and cytokines, and novel vaccine strategies; and using functional oncogenomics to inform the design of novel combination therapies. With continued rapid evolution of progress in these areas, MM will be a chronic illness with sustained complete response in a significant number of patients.

Discontinuation of Imatinib in Patients with CML and Sustained Complete Molecular Response (CMR) for Over 2 Years in the Japanese Population – An Interim Analysis of KEIO STIM Study,

Abstract 3765 Background:The introduction of imatinib mesylate in the treatment of chronic myeloid leukemia (CML) has dramatically changed its treatment outcome. The drug alone can induce durable hematologic, cytogenetic and molecular response, leading to a marked improvement of progression free survival (PFS). One of the next directions of treatment is to explore the possibility of long-term discontinuation of tyrosine kinase inhibitors (TKIs), and to identify the factors associated with sustained complete molecular response (CMR) after discontinuation. The French STIM study is the first large prospective trial to show that imatinib can be safely discontinued in a subset of patients who have maintained CMR for at least 2 years. We have performed a similar prospective study to confirm this result in the Japanese population. Purpose:To evaluate whether CMR will be sustained after stopping imatinib therapy, and to identify the clinical characteristics that could be associated with persistent CMR after drug discontinuation in the Japanese population. Method:Adult patients with CML, treated at Keio University Hospital, with sustained CMR (defined as negative quantitative and qualitative PCR of bcr-abl in the bone marrow) for over 2 years were enrolled in the study. After the discontinuation, patients were monitored monthly for the first 6 months and every 2 months thereafter, by peripheral blood quantitative PCR (TMA method; Amp-CML). Treatment with imatinib or one of the other TKIs was initiated if the Amp-CML value exceeded 100 copies. Patients:30 patients have been enrolled in the study at the time of the analysis. 20 patients (66.6%) were male. The median age of the patients was 54 (range 28 –77) years old. 11 patients (36.7%) had a previous history of interferon treatment. 20% of the patients were negative for CMV serology. The Sokal risk score was low in 19 (63.3%), intermediate in 7 (23.3%) and high in 2 (6.7%) patients. The median time on imatinib treatment was 92 (range 32–114) months and the median duration of CMR was 55.5 months, ranging from 24 to 94 months. The median daily dose of imatinib taken at the time of discontinuation was 400 mg (range 200–400). Results:The median follow-up of the patients at the time of this analysis was 5 months (range 1–6). Imatinib or one of the second generation TKIs were restarted in 11 patients (36.7%) (4 at month 2, 6 at month 3 and 1 at month 5; 3 were on imatinib, and 8 on dasatinib), leading to an estimated 6 months drug-free survival rate of 55.8%. All patients responded to either TKI. 5 patients have at least one positive PCR but the value have not exceeded 100 copies over time and have not been retreated by TKIs, leading to an estimated 6 months PCR-negative survival of 37.8%. According to the criteria of the French STIM study (positive and rising PCR value in two consecutive observation), an estimated 6 months relapse-free survival in our patient population was 46.8%. In comparing patients with sustained drug-free, relapse-free, or PCR-negative survival with those who did not, univariate or multivariate analysis did not show any significant difference for age, previous interferon treatment, duration of imatinib treatment, duration of CMR, sex, cytomegalovirus serology, peripheral blood NK or T cell subpopulation, or Sokal risk score. Although clinical side effects such as facial puffiness or muscle cramping markedly decreased with the discontinuation of imatinib, QOL analysis using SF-36 before and 2 months after the discontinuation did not show any significant improvement. Conclusion:Sustained CMR was achieved in a substantial proportion of patients who had been in CMR for over 2 years after the discontinuation of imatinib. All patients restarted on TKI treatment remained sensitive to treatment. There was no significant factor identified as a predisposing condition for sustained CMR in our patient population. However, our results are comparable to that of the previous French STIM study in terms of relapse-free survival, suggesting that there is no ethnic difference in the effect of stopping imatinib. This study is the first to evaluate the effect of imatinib discontinuation in the Asian population, and thus provides an important insight into the effect of imatinib and drug-free survival of CML patients in sustained CMR. Longer observation period and increased number of patients is necessary to draw a concrete conclusion, and to identify the factors relative to persistence of CMR. Disclosures:Okamoto:Bristol Myers Squibb: Honoraria, Research Funding; Novartis Pharma: Honoraria, Research Funding.

Imatinib Dose Interruption in Responding CML Patients Is Associated with Characteristic BCR-ABL Kinetics, Which Could Help to Differentiate Non-Adherence From Drug Resistance

Imatinib Dose Interruption in Responding CML Patients Is Associated with Characteristic BCR-ABL Kinetics, Which Could Help to Differentiate Non-Adherence From Drug Resistance

Complete Hematological, Molecular and Histological Remissions without Cytoreductive Treatment Lasting After Pegylated-Interferon α-2a (peg-IFNα-2a) Therapy in Polycythemia Vera (PV): Long Term Results of a Phase 2 Trial

Abstract▪280 Background:Two phase 2 studies have recently shown promising results of peg-IFNα-2a therapy in PV and essential thrombocythemia, including major efficacy, satisfactory tolerance, and significant molecular responses, renewing the interest for IFNα therapy in patients (pts) with MPN. However, no prospective study has assessed the long-term safety and efficacy of IFN therapy in those pts. We analyzed the long-term results of the PVN1 trial (www.clinicaltrials.gov #NCT00241241), a phase 2 study of peg-IFNα-2a therapy in PV, after a median follow-up (FU) of 6.4 years. Patients and methods:40 PV pts were enrolled in the study between Sept 04 and Sept 05. 4 pts were not evaluable (1 inclusion criteria violation, 2 withdraws of consent, 1 allergic reaction at first injection). Median age was 50 yrs (range 22–65). Median time since diagnosis was 6 months (range 1–65). 9 pts (25%) had previously received hydroxyurea. 6 pts (17%) had a history of thrombosis. 7 pts (20%) had splenomegaly. Long-term analyses were performed in 34 patients in June 11 (2 pts lost to FU). Hematological, molecular and histological responses were assessed according to the European LeukemiaNet (ELN) criteria. Results:Median FU was 77.4 months (mos) (Q1−Q3: 72 – 81 mos) and median duration of peg-IFNα-2a therapy was 47.4 mos (Q1-Q3: 28 – 77 mos). Clinical-hematological efficacy: At last evaluation, 32/34 pts (94%) were in hematological response including 28/34 complete responses (CR) (82%) and 4 partial responses (PR), and 2 pts had relapsed. 14 pts (41%) were still treated with peg-IFNα-2a for a median time of 70 mos. During FU, 20 pts stopped IFN after having received the drug for a median time of 42 mos. Among them, 10 pts (29% of the total cohort) had stopped because of sustained hematological CR, 8 (23%) because of toxicity, and 2 (6%) at investigator’s discretion. 13 (38% of the total cohort) of the 20 pts who stopped therapy did not received any other cytoreductive treatment after peg-IFNα-2a discontinuation, and 10/13 were still in hematological CR off-therapy at last evaluation after a mean observation period of 28+ mos (range 3+ – 64+ mos). During FU, PV relapsed in 3/13 pts who had stopped cytoreductive therapy after a mean time of 25 mos (range 6 – 37 mos). Peg-IFNα-2a was restarted in 2 of them and a second hematological CR was achieved. None of the patients experienced any vascular event during FU, when about 10 events would have been expected in this series of 34 PV pts followed for 77 mos (5.5% pts/year in the ECLAP study). Molecular and histological responses: Molecular response was assessed by measuring JAK2V617F allele burden in granulocytes (%V617F) in 29 pts with serial samples: a molecular response was achieved in 24 pts (83%) including 8 molecular CR (28%), and only 5 pts (17%) had no decrease in their %V617F. Mean %V617F was 47% (range 10 – 100%) at baseline, and 10% (range 0 – 45%) at 72 mos. 4 pts had a TET2 mutation: in none of them the TET2 mutant allele burden decreased during therapy although median decrease in %V617F in the same samples was 100% (Q1 – Q3: 75% – 100%). Bone marrow biopsies performed in some pts in hematological CR after discontinuation of peg-IFNα-2a found a normalized BM morphology fulfilling the ELN criteria for histological CR, and excluded an evolution to myelofibrosis as a cause for “apparent” remission. Toxicity: Peg-IFNα-2a was stopped because of adverse event in 8 pts (23%): fatigue in 2, depression in 1, grade 2 neuropathy in 1, arthralgia in 1, thyroiditis in 1, auto-antibodies in 1, liver enzyme elevation in 1 pt, respectively. Importantly, no unexpected adverse event was observed in spite of the very long-term use of peg-IFNα-2a (median of 45.5 mos). Conclusion:In this prospective phase 2 study of PV pts treated with peg-IFNα-2a after 6.4 years median FU, we recognized that: 1) 94% of pts were still in hematological response, including 82% CR; 2) 29% of pts could stop peg-IFNα-2a and remained in hematological response without further cytoreductive therapy after a median observation time of 28+ mos (up to 64+ mos); 3) major and sustained molecular response in %V617F was confirmed in 83% of patients, including 28% who achieved complete molecular response, while TET2 mutated clones appeared resistant to peg-IFNα-2a; 4) histological CR was also achieved in selected patients; 5) no vascular event was observed after 6.4 years median FU; 6) no new safety concern arose with prolonged utilization of peg-IFN alpha-2a. Disclosures:Off Label Use: Phase 2 study of pegylated-Interferon alpha-2a in polycythemia vera (off-label).

Multicenter Phase I Trial of Intraventricular Immuno-Chemotherapy in Recurrent CNS Lymphoma

Abstract 959 Background:We recently studied the safety and activity of intraventricular rituximab monotherapy in the treatment of recurrent intraocular and CNS non-Hodgkin lymphoma (NHL) (JCO 2007 25: 1350–1356). Rapid dissemination throughout the craniospinal axis was demonstrated and cytologic responses were detected in six out of ten patients. Two patients experienced improvement in intraocular NHL and one exhibited resolution of parenchymal NHL. The major goals of this current trial are to perform the first study of intraventricular immuno-chemotherapy in humans and to evaluate the safety of two dose levels of intraventricular rituximab as well as its pharmacokinetics in combination with intraventricular methotrexate (MTX). Secondary goals are to obtain information regarding the efficacy of this approach in the treatment of patients with recurrent CNS lymphoma, (brain parenchyma, intraocular or the leptomeningeal compartment). Methods:Thirteen patients with recurrent/refractory CD20+ CNS NHL were treated at UCSF, Dana Farber Cancer Institute and Massachusetts General Hospital on a phase I clinical trial involving twice weekly intraventricular rituximab at 10 mg and 25 mg dose levels, administered over a planned four week schedule. Rituximab is combined with MTX (12 mg) during the second intraventricular injection each week. Patients achieving partial response or better were eligible for a second month of combination intraventricular rituximab plus MTX. Results:No serious treatment-related toxicity has been detected with intraventricular rituximab/MTX at the 10 mg and 25 mg dose levels. The most common treatment-related toxicity was paresthesias (grade 1). One patient exhibited NHL progression outside of the CNS at three weeks and thus was not evaluable for CNS response, and one patient exhibited stable disease. Complete cytologic responses were detected in ten out of thirteen patients at the one-month restaging. Parenchymal responses were detected in three out of six subjects with one partial response within the corpus callosum, and two complete regressions of lesions within temporal lobe and cerebral cortex. One patient with leptomeningeal lymphoma non-responsive to intravenous rituximab and refractory to high-dose intravenous and intrathecal methotrexate, oral temozolomide and intrathecal liposomal cytarabine, obtained a sustained complete response with the intraventricular rituximab/MTX protocol and subsequently was approved for consolidative autologous stem cell transplant. Two patients have participated in extended dosing on protocol without progression for five and eight months respectively. Thus far, there is no evidence for a relationship between FcGR3A polymorphism and therapeutic resistance in a preliminary analysis (n=8 patients). The maximum tolerated dose of intraventricular rituximab with this combination was established as 25 mg. The mean maximum intraventricular rituximab concentration after intraventricular injection of rituximab was 285 microgram/ml at the 10 mg dose level (N=3) and 882 microgram/ml at the 25 mg dose level (N=10); (p<0.038). The rate of Rituximab clearance from the intraventricular compartment at two hours post injection was 30% slower when administered in combination with methotrexate compared to intraventricular rituximab monotherapy (p <0.02). Conclusions:Intraventricular rituximab/MTX appears to be safe in recurrent CNS NHL. Twelve of thirteen patients completed at least one month of therapy, without any treatment-associated serious adverse events at any of the institutions. Intraventricular administration of methotrexate may significantly attenuate rituximab clearance from the leptomeningeal compartment. There is encouraging evidence for significant activity of intraventricular immuno-chemotherapy in the treatment of drug-resistant CNS NHL, refractory or non-responsive to intravenous rituximab. These results provide strong support for further investigation of this novel therapeutic approach. NCT00221325. Supported by Leukemia and Lymphoma Society and NIH Grant CA13908301. Disclosures:Off Label Use: We will discuss the off-label use of rituximab within the leptomeningeal compartment to treat recurrent/refractory CNS lymphomas. Advani:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Treatment of polycythemia vera with imatinib mesylate

We treated 37 patients with polycythemia vera with imatinib mesylate (IM). The overall response rate was 49%. Thirty percent had a complete response, and 19%, a partial response. Thirty-one patients were treated for >120days. Frequent side effects included nausea, diarrhea, edema, and skin rash. Whereas IM was effective in controlling erythropoiesis and reducing spleen size it was ineffective in controlling thrombocytosis. Normocellular marrow developed in 4 patients who had a complete response. Progression to overt myelofibrosis occurred in 3. Nevertheless, 6 patients have had a sustained complete response while on IM for >6years. These patients were young, had high phlebotomy requirements, and only slightly elevated platelet counts. Therefore, we believe there may be a role for IM in patients with these characteristics whose disease cannot be controlled by, or as an alternative to, other myelosuppressive treatments.

Long-Term Outcome of Percutaneous Ablation in Very Early-Stage Hepatocellular Carcinoma

PurposeThe aim of this study was to investigate the long-term outcomes of percutaneous ablation (PA) of very early-stage hepatocellulcar carcinoma (HCC) with a multimodal strategy. MethodsWritten informed consent was obtained from all patients before treatment. Percutaneous ethanol injection (PEI) was performed for tumors in unfavorable locations; microwave ablation (MWA) was performed for tumors in favorable positions without a capsule; and radiofrequency ablation (RFA) was carried out in favorable tumors with a capsule. Since 2003, these advanced PA techniques have been used. ResultsEighty-three patients with very early HCC were treated with PA, including 33 with PEI, 19 with MWA, and 31 with RFA. Initial complete response (CR) was achieved in 79 patients (95%). The mean follow-up period was 45 ± 27 months (range, 24–155 months). Late treatment failure was observed in eight patients (10%), which was significantly associated with tumor size (P = 0.046) and technique advancements (P = 0.009). Sustained CR was achieved in 51 patients (61%) at the end of follow-up. Major complications occurred in two patients (2%). The 1-, 3-, 5-, and 6-year disease-free survival rates were 87%, 69%, 62%, and 59%, respectively. The 1-, 3-, 5-, and 7-year overall survival rates were 94%, 88%, 78%, and 74%, respectively. ConclusionsTreatment of very early-stage HCC using a multimodal strategy tailored to tumor characteristics achieves equivalent initial CR rates and long-term survival rates compared to surgical resection.

Predictors and scoring system for sustained complete response to conventional interferon-alpha therapy on chronic hepatitis B

To establish a predictive scoring system which may serve for the prediction of sustained response to conventional interferon-alpha (IFN-alpha) treatment on chronic hepatitis B. A total of 474 IFN-alpha treated hepatitis B virus e antigen (HBeAg)-positive patients were enrolled in the present study. The patients' baseline characteristics, such as age, gender, aminotransferases, activity grading (G) of intrahepatic inflammation, score (S) of liver fibrosis, hepatitis B virus (HBV) DNA and genotype were evaluated; therapy duration and response of each patient at the 24th wk after cessation of IFN-alpha treatment were also recorded. A predictive scoring system for a sustained complete response (CR) to IFN-alpha therapy was established based on genetic algorithm. About 10% of the patients were randomly drawn out as the test set. Responses to IFN-alpha therapy were divided into CR, partial response (PR) and non-response (NR). The mixed set of PR and NR was recorded as PR + NR. For the scoring system, the sensitivity and specificity were 78.8% and 80.6%, respectively. This SCR scoring system has satisfying prediction efficiency and is easily employed in clinical practice. With this scoring system, practitioners can propose individualized decisions that have an integrated foundation on both evidence-based medicine and personal characteristics.

Relapse of primary central nervous system lymphoma 13 years after high-dose methotrexate-based polychemotherapy

We report a now 74-year-old patient who was successfully treated with a methotrexate (MTX)-ssbased polychemotherapy protocol (Bonn protocol) for primary central nervous system lymphoma (PCNSL) in 1996. When presenting with an unusually late relapse after 13 years of tumor-free survival the diagnosis was made on the basis of clinical and radiological criteria. In the context of the very limited treatment options for recurrent PCNSL, it is reassuring that the re-application of high dose-MTX-based polychemotherapy, including intraventricular treatment, again succeeded in a sustained complete response with still low neurotoxicity.

Radiofrequency ablation of lung tumours

Pulmonary radiofrequency ablation (RFA) has become an increasingly adopted treatment option for primary and metastatic lung tumours. It is mainly performed in patients with unresectable or medically inoperable lung neoplasms. The immediate technical success rate is over 95%, with a low periprocedural mortality rate and 8–12% major complication rate. Pneumothorax represents the most frequent complication, but requires a chest tube drain in less than 10% of cases. Sustained complete tumour response has been reported in 85–90% of target lesions. Lesion size represents the most important risk factor for local recurrence. Survival data are still scarce, but initial results are very promising. In patients with stage I non-small-cell lung cancer, 1- and 2-year survival rates are within the ranges of 78–95% and 57–84%, respectively, with corresponding cancer-specific survival rates of 92% and 73%. In selected cases, the combination of RFA and radiotherapy could improve these results. In patients with colorectal lung metastasis, initial studies have reported survival data that compare favourably with the results of metastasectomy, with up to a 45% 5-year survival rate. Further studies are needed to understand the potential role of RFA as a palliative treatment in more advanced disease and the possible combination of RFA with other treatment options.

Combined Treatment of Large Hepatocellular Carcinoma with Transcatheter Arterial Chemoembolization and Percutaneous Ethanol Injection with a Multipronged Needle: Experimental and Clinical Investigation

This study was designed to evaluate the usefulness of percutaneous ethanol injection (PEI) with a multipronged needle for the treatment of large hepatocellular carcinoma (HCC). An experimental animal study and a clinical investigation were performed. In the experimental study, 20 ml of 99.5% ethanol was injected into porcine liver in vivo with a multipronged needle (n = 5) or a straight needle (n = 5), and the volumes of coagulation necrosis were compared. In the clinical investigation, PEI was performed in 17 patients (10 men, 7 women; mean age 73.4 ± 6.7 years) with single, large HCC (mean tumor diameter, 47.2 ± 11.5 mm; range, 32-70 mm) by using a multipronged needle. Fifteen of 17 patients received transarterial chemoembolization (TACE) before PEI. The volume of coagulation in porcine liver in vivo was significantly increased with the multipronged needle compared with the straight needle (longest perpendicular diameters, 34.2 ± 3.6 mm × 30.2 ± 3.6 mm vs. 22.6 ± 2.5 mm × 19 ± 2.2 mm, respectively; P < 0.05). In the clinical trial, initial complete response (CR) of the tumor was achieved in 17 of 17 patients, 7 of whom required two PEI sessions. During the follow-up, local recurrence was detected in 4 of 17 patients at 3-19 months after the procedure, for a rate of sustained local CR of 76%. No major complication occurred. Use of a multipronged needle substantially increases the volume of coagulation in vivo with respect to the conventional PEI technique. Combined TACE and PEI with multipronged needles is a safe and effective option for percutaneous treatment of single, large HCC.

Durable Complete Responses in Metastatic Colorectal Cancer Treated with Chemotherapy Alone

The median survival for patients with metastatic colorectal cancer (mCRC) has progressively increased over the past decades. Since the introduction of 5-fluorouracil (5-FU)-based chemotherapy, followed by hepatic resection of metastases, and more recently the adoption of newer chemotherapeutic regimens associated with targeted therapy, the gains are getting more substantial. Despite the recognition of the potential for long-term survival after surgical resection of metastatic disease, long-term survival data to determine the potential curative role of chemotherapy alone is lacking. We performed a retrospective review of 2751 patients who presented with mCRC at The MD Anderson Cancer Center from 1990 through 2003. Patients alive at 5 years who achieved complete response with chemotherapy and were not submitted to any surgical or interventional procedures directed to the metastatic sites were included in the analysis. The 5-year overall survival rate for all patients with mCRC during this period was 10.8%. Among these long-term survivors, 2.2% achieved a sustained complete response after chemotherapy (all 6 with fluoropyrimidines and 2 with irinotecan) as the only treatment modality and were without evidence of disease until the last follow-up visit (median of 10.3 years). This number corresponds to 0.24% (6 of 2541) of all patients with mCRC included in this review. Cure with chemotherapy alone is possible for a very small number of patients with metastatic colorectal cancer. Improved therapies are increasing complete response rates, but the impact of modern chemotherapy on durable complete responses will require additional follow up.

Abstract 4717: Final results from the Phase I study of MetMAb, a monovalent antagonist antibody to the receptor Met, dosed as single agent and in combination with bevacizumab in patients with advanced solid malignancies

Abstract Background: The receptor tyrosine kinase Met and/or its ligand, hepatocyte growth factor (HGF), are frequently over-expressed in cancers. Aberrant Met activation can enhance invasion, proliferation, and survival and may promote angiogenesis. MetMAb was uniquely engineered as a recombinant, humanized, monovalent monoclonal antibody to act as an antagonist of HGF-induced Met signaling. Materials and Methods: This 3+3 dose-escalation study consisted of three phases: 1) dose-escalation evaluating 1, 4, 10, 15, 20 and 30 mg/kg IV Q3W; 2) expansion at 15mg/kg IV Q3W; and 3) combination testing MetMAb, at 10 and 15mg/kg IV Q3W, plus bevacizumab (15mg/kg Q3W). Pre- and post- dose serum was collected for evaluation of pharmacodynamic biomarkers that could be affected by inhibition of Met and/or VEGF signaling. Results: 43 patients were treated in this study (21 in escalation, 13 in expansion, and 9 in combination). MetMAb has a half-life of approximately 11 days, and there were no apparent PK interactions with bevacizumab. MetMAb was generally well tolerated, both alone and in combination. The most frequent treatment-related adverse events included: fatigue, peripheral edema and hypoalbuminemia. In patients treated with the combination, no Grade 3-5 treatment-related adverse events were reported; a Grade 1, and dose-limiting adverse event of hemoptysis was reported in a patient who had central-necrosis of pulmonary metastases. A patient with gastric carcinoma achieved a complete response after 4 cycles of single-agent MetMAb; this patient came off study after 10 cycles with a sustained complete response. Conclusions: MetMAb, when administered as a single-agent, or in combination with bevacizumab was generally safe and well tolerated. A Phase II trial testing MetMAb in combination with bevacizumab and paclitaxel in patients with triple negative breast cancer is currently ongoing, while a Phase III trial testing MetMAb in combination with erlotinib in advanced NSCLC patients is planned. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4717. doi:10.1158/1538-7445.AM2011-4717

Complete Response in 5 Out of 38 Patients with Advanced Hepatocellular Carcinoma Treated with Stem Cell Differentiation Stage Factors: Case Reports from a Single Centre

Hepatocellular carcinoma (HCC) represents the third cause of cancer-related death. Because HCC is multi-centric with time, excluding the few transplanted patients, sooner or later it becomes untreatable with loco-regional therapies and, until some years ago, it was not responsive to systemic therapies. In 2005 a randomized trial indicated the efficacy of a product containing stem cell differentiation stage factors (SCDSF) taken from zebra fish embryos during the stage in which the totipotent stem cells are differentiating into the pluripotent adult stem cells. In such a trial the patients, with "intermediate" and "advanced" HCC according to BCLC/AASLD guidelines, presented benefit in terms of performance status (PS) and objective tumoral response, with some cases (2.4%) of complete response (CR). The aim of this cohort study is to report the experience of a tertiary referral center on the evidence of cases of CR in patients with "advanced" stage HCC treated with SCDSF as supportive care. CR was regarded as sustained disappearance of the neoplastic areas or blood supply therein, accompanied by normalization of AFP levels. Out of 49 patients consecutively recruited and retrospectively evaluated, 38 had "advanced" stage and 11 "terminal" stage. In 5 patients with "advanced" stage a sustained CR was reported (13.1%). Improvement on PS was obtained in 17 patients (34.6%). No side effects occurred. SCDSF treatment confirmed its efficacy in patients with "advanced" HCC, in terms of PS and tumoral response.