Rate Of Treatment-related Complications Research Articles

Remodeling Technique for Endovascular Treatment of Ruptured Intracranial Aneurysms Had a Higher Rate of Adequate Postoperative Occlusion than Did Conventional Coil Embolization with Comparable Safety

To compare the safety and efficacy of the remodeling technique with that of conventional coil embolization in a large multicenter series involving the endovascular treatment of ruptured intracranial aneurysms, the CLARITY study (Clinical and Anatomic Results in the Treatment of Ruptured Intracranial Aneurysms). The institutional review board approved the CLARITY study, and written informed consent was obtained from all patients. A total of 768 patients (age range, 19-80 years; mean age ± standard deviation, 51.0 years ± 11.1) with 768 ruptured aneurysms were treated with either conventional coil embolization (608 patients, 79.2%) or the remodeling technique (160 patients, 20.8%). Patient and aneurysm characteristics, the rate of adverse events related to the treatment or initial intracranial hemorrhage, and patient outcome were compared between treatment groups by using the χ(2), Fisher exact, or Student t test. The overall rate of treatment-related complications, with or without clinical manifestations, was 17.4% (106 of 608 patients) with coil embolization and 16.9% (27 of 160 patients) with remodeling (P = .999). The difference in the rates of thromboembolic events, intraoperative rupture, and early repeat bleeding between the treatment groups was not statistically significant. The cumulative morbidity and mortality rate related to the treatment in the remodeling group (3.8%, six of 160 patients) was similar to that in the coil embolization group (5.1%, 31 of 608 patients) (P = .678). Likewise, the global cumulative morbidity and mortality rates related to both the treatment and the initial hemorrhage did not differ significantly between groups (16.2% [26 of 160 patients] with remodeling and 19.6% [119 of 608 patients] with coil embolization, P = .366). The rate of adequate aneurysm occlusion, however, was significantly higher in the remodeling group (94.9%, 150 of 158 aneurysms) than in the coil embolization group (88.7%, 534 of 602 aneurysms) (P = .017). In our large series of patients treated for ruptured aneurysms, the remodeling technique-despite being performed in aneurysms with unfavorable characteristics-was as safe as conventional coil embolization and more efficacious in terms of the rate of adequate postoperative occlusion. These results indicate that the remodeling technique can be routinely used in the treatment of ruptured aneurysms.

Successful Reduced-Intensity Stem Cell Transplantation From Unrelated Cord Blood In Three Patients with X-Linked Severe Combined Immunodeficiency.

AbstractAbstract 4571Severe combined immunodeficiency (SCID) is the most severe form of the primary immunodeficiencies (PID), the most frequent type of which is X-linked SCID (X-SCID; T-B+NK-SCID). Hematopoietic stem cell transplantation (SCT) is the only curative treatment for these high-risk patients. Recently, some PID cases treated with unrelated cord blood stem cell transplantation (CBT) have been reported. To avoid severe infection during SCT and late complications, such as mental and growth retardation, reduced-intensity conditioning (RIC) regimens have been used for unrelated SCT for PID patients. However, reports of X-SCID patients receiving CBT with reduced-intensity stem cell transplantation (RIST) are quite limited. We report successful allogenic RIST from unrelated cord blood (CB) for treatment of X-SCID in our single centre. Three patients with X-SCID who had no HLA-matched sibling received unrelated CBT. Mutations in the common gamma chain gene were detected in all patients. Pre-transplantation conditioning for all patients consisted of fludarabine (FLU) (30 mg/m2/day) from day -7 to day -2 (total dose 180 mg/m2) and busulfan (BU) 4 mg/kg/day from day -3 to day -2 (total dose 8 mg/kg). All CB units were serologically matched HLA-A, B, and DR loci. Though two of the patients suffered from fungal or bacterial pneumonia before transplantation, there were no additional infectious complications during transplantation. All patients achieved engraftment with an absolute neutrophil count > 500/μ l with a mean of 22 days (range, 19–27 days), and they showed 100% donor chimerism by fluorescence in situ hybridization of their peripheral mononuclear cells using × and Y chromosome probes at one-year post transplantation. Full donor chimerism of both T and B cells was also confirmed. Only one patient (patient 2) developed grade III acute graft versus host disease (GVHD), which resolved with increased oral corticosteroid. None of the patients have developed chronic GVHD, received intravenous immunoglobulin replacements after the transplantations, or showed delayed psychomotor development during 21 to 77 months of follow-up. Only one patient (patient 3) had short stature (-2.4SD) at 21-month follow-up. The most commonly used RIC regimens worldwide have been the FLU/melphalan (LPAM) and the FLU/BU regimens. LPAM has broad stem cell toxicity to both primitive and committed stem cells, while BU may spare committed stem cells, resulting in early onset and a prolonged duration of neutropenia with the FLU/LPAM regimen. Moreover, it has been reported that the LPAM-containing conditioning regimen is a risk factor for hepatic veno-occlusive disease. Although conditioning regimens including standard-dose BU may be associated with a high rate of treatment-related complications due to organ toxicity, reduced-dose BU in combination with FLU is less myelosuppressive and less toxic than the FLU/LPAM regimen. Moreover, CBT has some advantages with regard to incidence and intensity of GVHD and availability compared with other alternative stem cell sources. Patients 1 and 2 had overcome pre-existing fungal and bacterial pneumonias, respectively, and recovered after transplantation. Thus, immediate SCT using an RIC regimen could be indicated for patients with X-SCID to reconstitute the immune system regardless of pre-existing infections. Since pre-existing infections are the principal risk factors for poor SCT outcomes, early diagnosis and transplantation before any infectious episodes is necessary for X-SCID patients. In conclusion, CBT is a suitable alternative to bone marrow transplantation for X-SCID patients requiring urgent SCT with no sibling donors. RIC consisting of FLU and BU is an effective and safe treatment for such cases. Disclosures:No relevant conflicts of interest to declare.

Comparison of Percutaneous Ultrasound-Accelerated Thrombolysis Versus Catheter-Directed Thrombolysis in Patients with Acute Massive Pulmonary Embolism

Acute massive pulmonary embolism (PE) is a life-threatening condition that requires prompt and aggressive interventions, including anticoagulation, catheter-directed thrombolysis (CDT), mechanical thrombectomy, or surgical thromboembolectomy. The aim of this study was to evaluate the treatment outcome in patients with massive PE who were treated with either ultrasound-accelerated thrombolysis using the EkoSonic Endovascular System (EKOS) or CDT intervention. During a recent 10-year period, the clinical records of all patients with massive PE undergoing catheter-directed interventions were evaluated. Patients were divided into two treatment groups: EKOS versus CDT interventions. Comparisons were made with regard to the treatment outcome between the two groups. Twenty-five patients underwent 33 catheter-directed interventions for massive PE during the study period. Among them, EKOS or CDT was performed in 15 (45%) and 18 (55%) procedures, respectively. In the EKOS group, complete thrombus removal was achieved in 100% cases. In the CDT cohort, complete or partial thrombus removal was accomplished in 7 (50%) and 2 (14%) cases, respectively. Comparing treatment success based on thrombus removal, EKOS treatment resulted in an improved treatment outcome compared with the CDT group (p < .02). The mean time of thrombolysis in EKOS and CDT group was 17.4 +/- 5.23 and 25.3 +/- 7.35 hours, respectively (p = .03). The mortality rate in the EKOS and CDT group was 9.1% and 14.2%, respectively (not significant). Treatment-related hemorrhagic complication rates in the EKOS and CDT group were 0% and 21.4%, respectively (p = .02). A significant reduction in Miller scores was noted in both groups following catheter-based interventions. No significant difference in relative Miller score improvement was observed between groups. Ultrasound-accelerated thrombolysis using the EkoSonic system is an effective treatment modality in patients with acute massive PE. When compared with CDT, this treatment modality provides similar treatment efficacy with reduced thrombolytic infusion time and treatment-related complications.

Incidence and Costs of Treatment-Related Complications Among Patients With Advanced Squamous Cell Carcinoma of the Head and Neck

To evaluate the incidence and costs of complications due to radiotherapy alone vs platinum-based chemoradiotherapy among patients diagnosed as having advanced squamous cell carcinoma of the head and neck (ASCCHN) from a payer perspective. Retrospective cohort study. Data from the PharMetrics Patient-Centric Database from June 2000 through June 2006. The study included patients with ASCCHN and an indication of a secondary malignant neoplasm (both identified based on International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis codes), 124 of whom were treated with radiotherapy alone and 77 of whom were treated with chemoradiotherapy (including 53 with cisplatin plus radiotherapy, 26 with carboplatin plus radiotherapy, and 2 with cisplatin and carboplatin plus radiotherapy). The patients were assigned to 1 of 2 cohorts based on treatment type-radiotherapy only and platinum-based chemoradiotherapy-and were followed up for 6 months. Incidence and costs of treatment-related complications associated with chemotherapy in ASCCHN. We found significantly (P < .001) higher rates of treatment-related complications among patients receiving chemoradiotherapy (86%) than among patients receiving only radiotherapy (51%). The mean per-patient costs associated with treatment-related complications were approximately $10 000 higher among patients who received chemoradiotherapy than among those treated with radiotherapy alone (P < .001). These costs represented 17% of the total costs during follow-up for patients who received chemoradiotherapy and 11% of costs for those who received radiotherapy. The most expensive complications were dehydration and/or electrolyte imbalance and oral complications. Our study results suggest that the attributable incidence and costs of treatment-related complications associated with chemotherapy in ASCCHN are substantial. The emergence of safer treatments may have the advantage of alleviating this cost burden.

Angular Stable Fixation of Proximal Humeral Fractures

Proximal humeral fractures requiring surgical stabilization remain a therapeutic challenge. High rates of treatment-related complications have been reported to be associated, particularly in elderly patients with unstable fracture types and diminished bone quality. In recent years, angular stable implants have been introduced to improve the patients' outcome. The purpose of this study was to assess the clinical and radiographic long-term results after angular stable plate fixation of proximal humeral fractures at this Level I trauma center, with special emphasis on fracture healing, functional outcome and treatment related complications. We retrospectively analyzed functional and radiographic results of 42 patients (average age: 57.8 years) after angular stable plate fixation of proximal humeral fractures at an average time of 3.2 (+/-0.8) years after trauma. Functional results were defined by the Constant shoulder score (CS) and the individual Constant score (CSindiv). Radiographic results were assessed by a three-view trauma series (anteroposterior, lateral, and axillary view). For operative treatment, two different angular stable implants were used. Twenty-seven patients were stabilized by a HOFER plate, fifteen patients by a Locking Proximal Humerus Plate. Clinical results revealed an average CS of 74.0 points and an average individual CSindiv of 79.2% points. Fourteen patients had an excellent functional outcome, eight patients a good outcome and fourteen patients had moderate functional results. Six patients (14%) had a poor outcome with less than 55% on CSindiv. Regarding the radiographic outcome, we had an overall union rate of 95% (40 of 42). Failures of reduction and fixation occurred in fourteen patients (33%), and in nine patients (21%) we had signs of a humeral head necrosis. Re-operation due to treatment-related complications was necessary in two patients (5%). Statistical analysis revealed that the fracture type and the age of the patients had a significant influence on the clinical outcome and on the incidence of treatment-related complications. With regards to fracture healing and functional outcome of the patients, we had a satisfactory outcome after angular stable plate fixation of proximal humeral fractures. However, we experienced a notably high rate of technical failures and partial humeral head necrosis. Advanced surgical skills and experiences are necessary to achieve correct anatomic reduction and implant fixation, to reduce the risk of these treatment-related complications.

Latest progress in treatment of gynaecological cancers

The present report gives the scope of relevant contributions focusing on the treatment of gynaecologic malignancies presented at the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO) held from May 30 to June 3, 2008 in Chicago, Illinois. Some new data will directly influence the routine in gynaecologic oncology, while other data have to await their confirmation in ongoing studies until their clinical impact can be definitively evaluated. Regarding the radiotherapeutic adjuvant management of intermediate-high-risk endometrial cancers, the PORTEC-2 trial clearly demonstrated the non-inferiority of vaginal brachytherapy (VBT) as compared with external beam radiotherapy (EBRT) of the whole pelvis with regard to disease-free and overall survival and revealed a higher rate of treatment-related complications and side-effects for EBRT and consequently a higher quality of life in patients treated with VBT. In chemotherapeutic management of advanced and recurrent cervical cancer the four-armed GOG 204 trial demonstrated the best therapeutic index for the cisplatin-paclitaxel regimen. Hence, the authors advocated that this doublet should be used as a control arm in further GOG protocols investigating this setting. Fundamental changes in the routine first-line chemotherapy for ovarian cancer should be expected from the outcome of the phase III Japanese Gynecologic Oncology Group trial that revealed a survival benefit for weekly dose-dense administration of paclitaxel as compared with standard three-weekly carboplatin-paclitaxel.

Radiation Therapy Field Extent for Adjuvant Treatment of Axillary Metastases From Malignant Melanoma

To compare treatment-related outcomes and toxicity for patients with axillary lymph node metastases from malignant melanoma treated with postoperative radiation therapy (RT) to either the axilla only or both the axilla and supraclavicular fossa (extended field [EF]). The medical records of 200 consecutive patients treated with postoperative RT for axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients received postoperative hypofractionated RT for high-risk features; 95 patients (48%) received RT to the axilla only and 105 patients (52%) to the EF. At a median follow-up of 59 months, 111 patients (56%) had sustained relapse, and 99 patients (50%) had died. The 5-year overall survival, disease-free survival, and distant metastasis-free survival rates were 51%, 43%, and 46%, respectively. The 5-year axillary control rate was 88%. There was no difference in axillary control rates on the basis of the treated field (89% for axilla only vs. 86% for EF; p = 0.4). Forty-seven patients (24%) developed treatment-related complications. On both univariate and multivariate analyses, only treatment with EF irradiation was significantly associated with increased treatment-related complications. Adjuvant hypofractionated RT to the axilla only for metastatic malignant melanoma with high-risk features is an effective method to control axillary disease. Limiting the radiation field to the axilla only produced equivalent axillary control rates to EF and resulted in lower treatment-related complication rates.

Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice?

If liver transplantation is not feasible, partial resection is considered the treatment of choice for hepatocellular carcinoma (HCC) in patients with cirrhosis. However, in some centers the first-line treatment for small, single, operable HCC is now radiofrequency ablation (RFA). In the current study, 218 patients with single HCC <or= 2.0 cm (very early or T1 stage) underwent RFA. We assessed 2 primary end points that could be easily compared with those reported for resective surgery: (1) the rate of sustained, local, complete response and (2) the rate of treatment-related complications. The secondary end point was 5-year survival in the 100 patients whose tumors had been considered potentially operable. After a median follow-up of 31 months, sustained complete response was observed in 216 patients (97.2%). In the remaining 6, percutaneous ethanol injection, selective intraarterial chemoembolization, or resection were used as salvage therapy. Perioperative mortality, major complication, and 5-year survival rates were 0%, 1.8%, and 68.5%, respectively. Compared with resection, RFA is less invasive and associated with lower complication rate and lower costs. RFA is also just as effective for ensuring local control of stage T1 HCC, and it is associated with similar survival rates (as recently demonstrated by 2 randomized trials). These data indicate that RFA can be considered the treatment of choice for patients with single HCC <or= 2.0 cm, even when surgical resection is possible. Other approaches can be used as salvage therapy for the few cases in which RFA is unsuccessful or unfeasible.

A Phase I/II Trial of Chemoembolization for Hepatocellular Carcinoma Using a Novel Intra-Arterial Drug-Eluting Bead

To assess the safety and efficacy of transarterial chemoembolization (TACE) using doxorubicin-eluting beads (DEB) for hepatocellular carcinoma (HCC). Patients with incurable HCC and Child-Pugh class A cirrhosis were considered eligible for this phase I/II trial. Two courses of TACE using DEB were given at an interval of 2 months, and tumor response was assessed by computerized tomography scan. The phase I trial was a dose-escalating study starting from 25 mg to 150 mg doxorubicin in cohorts of 3 patients. The 150-mg doxorubicin dose was used for the phase II study. Primary end points were treatment-related complications and deaths. Secondary end points included tumor response and pharmacokinetics of doxorubicin. In the phase I study involving 15 patients, no dose-limiting toxicity was observed for up to 150 mg doxorubicin, which was used for 20 patients in the phase II study. The pharmacokinetic study showed a low peak plasma doxorubicin concentration (49.4 +/- 23.7 ng/mL), and no systemic toxicity was observed. The treatment-related complication rate was 11.4%. There was no treatment-related death. Among 30 patients who completed 2 courses of TACE, the partial response rate and the complete response rates were 50% and 0%, respectively, by response evaluation criteria in solid tumors (RECIST) criteria at computerized tomography scan 1 month after the second TACE. By modified RECIST criteria, taking into account the extent of tumor necrosis, 19 (63.3%) patients had a partial response and 2 (6.7%) had a complete response. This study shows that TACE using DEB is a safe and effective treatment for HCC, supporting a phase III randomized trial to compare this novel treatment with conventional TACE using doxorubicin-Lipiodol emulsion.

Favorable Outcome for Adolescents With Acute Lymphoblastic Leukemia Treated on Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium Protocols

Historically, adolescents with acute lymphoblastic leukemia (ALL) have had inferior outcomes when compared with younger children. We report the outcome of adolescents treated on Dana-Farber Cancer Institute (DFCI; Boston, MA) ALL Consortium Protocols conducted between 1991 and 2000. A total of 844 patients aged 1 to 18 years, with newly diagnosed ALL were enrolled onto two consecutive DFCI-ALL Consortium Protocols. We compared outcomes in three age groups: children aged 1 to 10 years (n = 685), young adolescents aged 10 to 15 years (n = 108), and older adolescents aged 15 to 18 years (n = 51). With a median follow-up of 6.5 years, the 5-year event-free survival (EFS) for those aged 1 to 10 years was 85% (SE, 1%), compared with 77% (SE, 4%) for those aged 10 to 15 years, and 78% (SE, 6%) for those aged 15 to 18 years (P = .09). Adolescents were more likely to present with T-cell phenotype (P < .001) and less likely to have the TEL-AML1 fusion (P = .05). The incidence of pancreatitis and thromboembolic complications, but not asparaginase allergy, was higher in patients 10 years of age compared with those younger than 10 years. However, there was no difference in the rate of treatment-related complications between the 10- to 15-year and 15- to 18-year age groups. Adolescents were more likely to present at diagnosis with biologically higher risk disease (T-cell phenotype and absence of the TEL-AML1 fusion) and more likely to experience treatment-related complications than younger children. However, the 5-year EFS for older adolescents was 78% +/- 6%, which is superior to published outcomes for similarly aged patients treated with other pediatric and adult ALL regimens. Based on this experience, we currently are piloting our regimen in patients aged 18 to 50 years.

Treatment of comorbidities besides the treatment of primary tumor may further increase effective management of cancer

For most of the patients with cancer comorbidity had independent prognostic effect. This negative influence of comorbidity on survival of cancer might be due to several mechanisms: the increased risk of death due to the comorbid condition itself, more contra-indications for anti-cancer treatment, more indications for dose reduction and a higher rate of treatment-related complications, such as infections and cardiovascular events. It is known that in some chronic diseases (e.g., coronary artery disease, hypertension, and obesity) pro-angiogenic growth factors are increased compared to controls and mostly normalized after specific treatment. We propose that increased pro-angiogenic growth factor levels in cancer patients due to comorbidities may lead to the progression of the tumors and poor prognosis. Treatment of comorbidities besides the treatment of primary tumor may further increase effective management of cancer.

Salvage rectal surgery: Overview

Recurrence of the disease represents the major problem in patients who undergo "curative" resection for rectal cancer, with published rate ranging from 3 to 50%. Most relapses occur within first two years of follow-up. Depending on the site of the recurrence, it can be local or distant. It also can be solitary or diffuse. In terms of potential surgical cure the best results are achieved with solitary, localized metastases. The most common sites of the solitary metastases are pelvis, liver and lung, with a fairly even distribution among these three sites. Other sites of the localized metastases can be peritoneum, lymph nodes, brain, bone, abdominal wall, ureter and kidney. These sites are less common, but not so amenable to resection. Local recurrence varies depending on the original type of surgery. It can be stated that surgical technique directly influences local recurrence rate in patients with rectal cancer. According to the results from a number of different authors 5-year survival rate after reresection is 2-13% of all patients with locally recurrent cancer, both alone and associated with distant metastases. The most important moment in this problem is to decide when not to operate. The absolute contraindications for salvage surgery are: "frozen pelvis", aneuploid tumors and those with mucinous component, clinical or CT evidence of invasion of the pelvic nerves, lymphatics or veins, or ureter bilaterally. Also, evidence of involvement of the lateral pelvic sidewalls and/or upper sacral marrow, and/or S2 is an absolute contraindication for surgery. Thus, main goals of this type of surgery are respectively: palliation of symptoms, a good quality of life and, if possible, cure with low treatment-related complication rates.

Preoperative Multimodality Treatment of Localized Soft Tissue Sarcoma: Addition Through Subtraction?

In this issue of Annals of Surgical Oncology, Mack and colleagues from the Tom Baker Cancer Center at The University of Calgary report their results with preoperative intravenous or intra-arterial doxorubicin and short-course, high-dose-per-fraction (10 fractions of 3 Gy each) radiotherapy followed by wide local resection for selected patients with extremity soft tissue sarcomas. The authors report remarkably low treatment-related complication rates, and in the subset of patients who underwent preoperative chemoradiation followed by macroscopically and microscopically complete (R0) surgical resection, a 97% 5-year local control rate was observed. Can this regimen serve as a therapeutic maquette, or are these results best regarded as aleatoric, as are many findings in clinical research? This report raises a number of important issues that warrant further consideration and discussion. These include the important issues of patient selection, complication rates, radiation fractionation and schedule, and the relative contributions of chemotherapy, radiation, and patient selection to these results. Historical background is relevant in understanding the rational underpinning of the treatment approach used by Mack and colleagues. This approach has its roots in the protocols developed two decades earlier at the University of California, Los Angeles (UCLA) by Eilber et al. The UCLA group adopted large-dose-per-fraction preoperative radiotherapy (10 fractions of 3.5 Gy each) to overcome the putative radioresistance of soft tissue sarcomas. The investigators were influenced in their regimen design by the observation that irradiation of some melanoma cell lines resulted in a large initial shoulder on the cell survival curve, although later evidence suggested that this may not be consistent. Nonetheless, the potential radioresistance of melanoma and, by extension, sarcoma was attributed to the tumor cells capacity for repair of sublethal damage implied by this shoulder. This preclinical speculation led to pilot studies performed in patients with soft tissue sarcoma by Eilber et al. and others that established the relative toxicities and local control rates associated with short-course, highdose-per-fraction radiation and concurrent intraarterial or intravenous anthracycline-based chemotherapy. On the basis of these pilot studies, a handful of centers, including the Tom Baker Cancer Center, adopted this approach as their standard therapy for patients with localized soft tissue sarcomas. Patient selection is one of the many issues that should be considered in the interpretation of the Tom Baker Cancer Center experience with the modified UCLA regimen. In the abstract and introduction, Mack and colleagues report that their chemoradiation approach was used in all patients who presented with soft tissue sarcomas of the extremity and trunk between 1984 and 1996, and their results are presented as a consecutive series. However, in the Methods section, the authors clarify that they excluded patients who were believed to have tumor involvement of major nerves or bone. They do not indicate what specific clinical or Received June 2, 2005; accepted June 3, 2005; published online June 29, 2005. Address correspondence and reprint requests to: Peter W. T. Pisters, MD, FACS; E-mail: ppisters@mdanderson.org

Intensive chemoradiotherapy as a primary treatment for organ preservation in patients with advanced cancer of the head and neck: efficacy, toxic effects, and limitations.

To evaluate the efficacy and toxic effects of intensive chemoradiotherapy as a primary modality for organ preservation in patients with advanced squamous cell carcinoma of the head and neck (SCCHN) and to define the patterns of treatment failure associated with this therapy. Retrospective review. Tertiary care referral center. A total of 127 consecutive patients with advanced SCCHN treated with primary concurrent chemoradiotherapy. Efficacy data included the rates of tumor response to therapy, organ preservation, disease recurrence, overall and disease-specific survival, and patterns of treatment failure. Toxic effect data included the rate and grade of treatment-related complications and the rate of unscheduled hospital admissions for managing treatment-related toxic effects. Ninety-six patients (76%) were men and 31 (24%) were women. Average age at diagnosis was 62 years (range, 37-85 years). The primary tumor site was the oropharynx in 58 patients (46%), the larynx in 36 (28%), the hypopharynx in 20 (16%), the oral cavity in 10 (8%), and another site in 3 (2%). Most patients (91%) had stage III or IV disease. Average follow-up was 36 months. Primary chemoradiotherapy achieved complete response at the primary tumor site in 109 patients (86%). Patients with partial response, stable or progressive disease, or recurrence at the primary site underwent salvage surgery. Overall, at mean follow-up of 3 years, local disease control was achieved in 113 patients (89%), and organ preservation was possible in 102 patients (80%). Two thirds of all patients (n = 83) had clinical N+ disease. Complete clinical response to chemoradiotherapy in the neck was achieved in 57 of these patients (69%). However, complete response to chemoradiotherapy was 93%, 62%, and 47% for N1, N2, and N3 disease, respectively (P <.001). Patients achieving less than complete clinical response underwent salvage neck dissection. Overall, at an average follow-up of 36 months, regional disease control was achieved in 76 (92%) of the 83 patients with neck metastasis. Despite this high locoregional control rate, distant metastasis occurred in 18 patients (14%), was the most common site of disease recurrence (53%), and accounted for almost 40% of all treatment failures. Severe (grade 3 or 4) mucositis and neutropenia occurred in 33% and 25% of patients, respectively. Two patients (2%) died of treatment-related toxic effects. At 3-year mean follow-up, disease-specific and overall survival were 72% and 57%, respectively. Most deaths were due to distant metastasis, comorbidity, and second primary tumors. High rates of locoregional disease control and organ preservation are achievable with primary chemoradiotherapy in patients with advanced SCCHN, but they are associated with severe treatment-related toxic effects. Despite this effective local and regional disease control, improved survival is hampered by the relatively high incidence of distant metastasis, second primary tumors, and comorbidity.

The Choice of Treatment Method for Unruptured Cerebral Aneurysm

To compare complications, anigographical results, duration of postoperative hospital stay and cost for treatment of surgical clipping and coil embolization in the treatment of unruptured cerebral aneurysm. One hundred and nine non-giant saccular aneurysms in 90 patients were treated by either endovascular treatment (E group) or direct surgery (S group) in our Neurosurgical Department between April 1996 and April 2002. The complications and angiographical results were reviewed. The duration of postoperative hospital stay and cost for the treatment were calculated from bills for health insurance for 38 operations and 12 embolizations in 47 patients whose aim of hospitalization was only treatment for their unruptured aneurysm. Neck clipping was performed for 89 aneurysms (S group), wrapping for four (S group), embolization using Guglielmi's detachable coils (GDCs) for 15 (E group), and failed embolization followed by clipping for one (E group). The postoperative temporary deficit (disappeared within one month) and permanent deficit was seen in five cases (6.7%) and in three cases (morbidity: 4.0%) of S group, and in one case (6.7%) and none (morbidity; 0%) of E group, respectively. No death was seen in both group (mortality; 0% in both group). The rate of angiographical complete occlusion of the aneurysm was significantly higher in S group (P = 0.015, 88% in S group vs 50% in E group). The postoperative hospital stay was significantly shorter in E group (P= 0.000013, mean days: 17.1 in S group vs 6.3 in E group), but cost for treatment was rather cheep in S group (N.S., mean cost: 1684329 yen in S group vs. 2259011 in E group). This retrospective study suggested that surgical treatment may be less expensive treatment with higher rate of postoperative angiographical complete occlusion than coil embolization, and treatment-related complication rate was similar in both treatment.

Ageism in rectal carcinoma? Treatment and outcome variations.

Rectal cancer adjuvant and neo-adjuvant therapies are associated with improved survival and local control rates. Concerns regarding adverse treatment effects tend to reduce administration in the elderly-the very population this disease affects. To determine the extent to which age alters rectal cancer treatment and its outcome. Using the population based provincial cancer registry, patients with adenocarcinoma of the rectum diagnosed between 1991 and 1998 were identified. From this cohort, a random subsample of patients seen at the regional cancer center were selected for detailed analysis. Demographic and clinical data between the provincial cohort and the subsample were compared for homogeneity. Log rank tests and Kaplan-Meier survival estimates were carried out on the subsample. The population cohort (n = 1979) and the subsample (n = 259) were similar in age, sex, and treatment distributions. Elderly patients (>/=75 yr) made up 23% of the rectal cancer population in Alberta. Age had a highly significant (p = 0.001) impact on whether patients received surgery alone or had surgery plus chemoradiotherapy. This corresponded to a considerable survival advantage for those elderly patients who did receive multimodality therapy (p = 0.008). The advantage of multimodality therapy in rectal cancer is confirmed in this populationbased study. Although a significant number of elderly patients are fit enough to tolerate major surgery they are being denied adjuvant therapies, presumably on the basis of potentially high treatment-related complication rates, with a subsequent reduction in survival. Strategies must be developed to ensure that maximum treatment benefit is obtained without increased harm in the elderly rectal cancer patient.

Ex vivo expansion of normal progenitor cells from acute myeloid leukemia cell-contaminated CD34+ peripheral blood progenitor cells after mafosfamide purging.

The rationale for purging of autologous acute myeloid leukemia (AML) grafts is to eradicate contaminating leukemic cells that might contribute to relapse. However, in vitro purging generally delays post-transplant hematopoietic recovery, thus increasing treatment-related complication rates. Theoretically, this prolonged aplasia might be shortened by the additional transplantation of ex vivo-generated progenitor cells. Therefore, we investigated whether nonleukemic progenitors could be expanded ex vivo from AML cell-contaminated CD34(+) peripheral blood progenitor cell (PBPC) preparations. Nonleukemic CD34(+)-selected PBPC and AML cells (Kasumi-1, KG-1, primary AML blasts) were cultured in cytokine-supplemented liquid culture for up to 19 days. Cells were used either unmanipulated or following in vitro purging with mafosfamide (30, 50, 75 microg/ml). Ex vivo-generated cells were assessed by flow cytometry, progenitor cell assays, and polymerase chain reaction. Without prior purging, ex vivo culture markedly amplified AML cells as well as nonleukemic CD34(+) PBPC (day 12: Kasumi-1, 18.5 +/- 0.6-fold; KG-1, 52.2 +/- 2.6-fold; CD34(+), 74.1 +/- 5.6-fold). Co-culture with leukemic cells did not affect CD34(+) cell growth and vice versa. Following in vitro purging, CD34(+) PBPC were expanded even at the highest mafosfamide dose (day 19: 25 +/- 15-fold), whereas leukemic cells were markedly depleted (approx. 1.5 log). Furthermore, normal colony-forming units (CFU) could be effectively recovered (day 19: 10 +/- 3.1% of prepurging input CFU), whereas CFU-L were depleted to undetectable levels in six of seven experiments. Finally, leukemic cells were undetectable following ex vivo co-culture of purged cells (CD34(+) PBPC plus 10% Kasumi-1 cells or primary blasts), but were clearly detectable without purging. Taken together, these data demonstrated that ex vivo expansion of normal progenitors from mafosfamide-purged AML cell-contaminated grafts might be feasible.

Fractionated stereotactic radiosurgery and preservation of hearing in patients with vestibular schwannoma: a preliminary report.

Microsurgery and stereotactic radiosurgery (SRS) for vestibular schwannomas are associated with a relatively high incidence of sensorineural hearing loss. A prospective trial of fractionated SRS was undertaken in an attempt to preserve hearing and minimize incidental cranial nerve injury. Thirty-three patients with vestibular schwannomas were treated with 2100 cGy in three fractions during a 24-hour period using conventional frame-based linear accelerator radiosurgery. The median tumor diameter was 20 mm (range, 7-42 mm). Baseline and follow-up evaluations included audiometry and contrast-enhanced magnetic resonance imaging. End points were tumor progression, preservation of serviceable hearing, and treatment-related complications. Thirty-one patients (32 tumors) were assessable for tumor progression and treatment-related complications and 21 patients for preservation of serviceable hearing, with a median follow-up interval of 2 years (range, 0.5-4.0 yr). Tumor regression or stabilization was documented in 30 patients (97%) and tumor progression in 1 (3%). The patient with tumor progression remains asymptomatic and has not required surgical intervention. Five patients (16%) developed trigeminal nerve injury at a median of 6 months (range, 4-12 mo) after SRS; two of these patients had preexisting trigeminal neuropathy. One patient (3%) developed facial nerve injury (House-Brackmann Class 3) 7 months after SRS. Preservation of useful hearing (Gardner-Robertson Class 1-2) was 77% at 2 years. All patients with pretreatment Gardner-Robertson Class 1 to 2 hearing maintained serviceable (Class 1-3) hearing as of their last follow-up examination. Three-fraction SRS with a conventional stereotactic frame is feasible and well tolerated in the treatment of acoustic neuroma. This study demonstrates a high rate of hearing preservation and few treatment-related complications among a relatively high-risk patient cohort (tumors >15 mm or neurofibromatosis Type 2). Longer follow-up will be required to assess the durability of tumor control.

Estimating Treatment Benefits for the Elderly: The Effect of Competing Risks

To fully involve patients in treatment decisions, physicians need to communicate future health prospects that patients will have both with and without newly diagnosed disease. These prospects depend not only on the risks patients face from the new disease but also on the risks they face from other causes. Nowhere is an understanding of these competing risks more relevant than in the care of the elderly. In this study, we use the declining exponential approximation for life expectancy (DEALE) to provide a framework to help clinicians gauge the effect of competing risks as a function of age. Because older patients have many competing risks for death, the absolute effect of a new diagnosis on life expectancy is often relatively small. Consequently, the potential gain in survival even from perfect therapy may also be small. Moreover, no therapy is perfect, and the risks of therapy often increase with age. In the elderly, the combination of a high burden of competing risks and high rates of treatment-related complications conspires to reduce the net benefit of numerous interventions. We conclude that, compared with younger patients, the elderly should request only the more clearly effective treatments and should be willing to tolerate fewer associated complications before they agree to initiate therapy.

A prospective randomized comparison of transurethral resection to visual laser ablation of the prostate for the treatment of benign prostatic hyperplasia

Objectives Transurethral resection of the prostate (TURP) represents the accepted standard of surgical therapy for the management of symptomatic bladder outlet obstruction due to benign prostatic hyperplasia (BPH). However, this is a major operative procedure associated with significant perioperative morbidity. Visual laser ablation of the prostate (VLAP) utilizing a neodymium:yttrium-aluminum-garnet laser represents a new technologic approach to the surgical management of BPH. We compared the relative safety and efficacy of these two surgical approaches in a prospective, randomized trial. Methods At 6 investigational sites in the United States, 115 men with symptomatic BPH more than 50 years of age and not in retention, were randomly assigned to undergo either TURP (59 patients) or VLAP (56 patients). VLAP patients received a mean of 10,200 J of energy delivered in a mean of 5.5 intraprostate laser applications. At preoperative baseline, 3 months, 6 months, and 1 year postoperatively, all patients underwent clinical evaluations, including ultrasonic prostatic volume determination, standardized American Urological Association (AUA)-6 symptom score, peak urine flow, postvoid residual urine volume, and quality-of-life assessment. Results Compared to TURP, the VLAP procedure required less time (23.4 versus 45.2 minutes; P <0.01) and shorter hospitalization (1.8 versus 3.1 days, P <0.01). VLAP was associated with a significantly lower rate of serious treatment-related complications compared to TURP (10.7% versus 35.6%; P <0.01). Only one (2.2%) patient undergoing VLAP experienced a greater than 2.2 g/dL decrease in hemoglobin compared to 40% of TURP patients ( P = 0.01). No patient in the VLAP group required blood transfusion compared with 3.4% of those undergoing TURP. Of the 115 patients, clinical outcomes measured at 1 year showed a mean improvement in AUA-6 symptom scores of −9.0 for VLAP compared with −13.3 for TURP ( P <0.04), mean increase in peak urinary flow rate of 5.3 cc/s for VLAP compared with 7.0 cc/s for TURP ( P = 0.27), and mean decrease in postvoid residual urine volume of −55.4 cc for VLAP compared with −138.8 cc for TURP ( P < 0.01). At 1 year, 78.2% of patients undergoing VLAP indicated that their quality of life was improved compared with 93.0% of patients undergoing TURP ( P = 0.03). When compared with TURP, treatment of BPH with VLAP is associated with less hemoglobin decrease, a lower likelihood of serious complication, and requires less procedure time and a shorter hospital stay. Through a 1-year follow-up, VLAP produced significant improvement over baseline in objective and subjective outcome measures. However, for 1 -year improvement in AUA-6 symptom score, postvoid residual urine volume, and quality of life, VLAP was less effective than TURP. Conclusions In this initial study in the United States, with relatively low-energy laser applications, VLAP did not result in as complete a removal of prostatic tissue as did TURP. Considering the lower morbidity, shorter procedure and hospitalization times, and the degree of effectiveness that was achieved even at the low-energy doses used in this study, VLAP appears to be a viable and safe alternative to standard TURP.