Risk Of Further Relapse Research Articles

Association of Disease-Modifying Treatment With Outcome in Patients With Relapsing Multiple Sclerosis and Isolated MRI Activity.

Isolated value of MRI metrics in relapsing multiple sclerosis (RMS) as a surrogate marker of response to disease-modifying treatment (DMT) and, thus, as decision criteria for DMT escalation in the absence of clinical signs of disease activity is still a matter of debate. The aim of this study was to investigate whether DMT escalation based on isolated MRI activity affects clinical outcome. Combining data from 5 MS centers in Austria and Switzerland, we included patients with RMS aged at least 18 years who (1) had initiated first-line, low-to-moderate-efficacy DMT (interferon β, glatiramer acetate, teriflunomide, or dimethyl fumarate) continued for ≥12 months, (2) were clinically stable (no relapses or disability progression) on DMT for 12 months, (3) had MRI at baseline and after 12 months on DMT, and (4) had available clinical follow-up for ≥2 years after the second MRI. The primary endpoint was occurrence of relapse during follow-up. The number of new T2 lesions (T2L) and DMT strategy (continuing low-/moderate-efficacy DMT vs escalating DMT) were used as covariates in regression analyses. A total of 131 patients with RMS, median age of 36 (25th-75th percentiles: 29-43) years, 73% women, were included and observed over a median period of 6 (5-9) years after second MRI. Sixty-two (47%) patients had relapse. Patients who continued first-line DMT had a 3-fold increased risk of relapse given 2 new T2L (hazard ratio [HR] 3.2, lower limit [LL] of 95% CI: 1.5) and a 4-fold increased risk given ≥3 new T2L (HR 4.0, LL-CI: 2.1). Escalation of DMT lowered the risk of relapse in patients with 2 new T2L by approximately 80% (HR 0.2, upper limit [UL] of 95% CI: 1.3) and with ≥3 new T2L by 70% (HR 0.3, UL-CI: 0.8). In case of only 1 new T2L, the increased risk of relapse and the treatment effect did not reach statistical significance of 5%. In our real-world cohort of patients clinically stable under low-to-moderate-efficacy DMT, escalation of DMT based on isolated MRI activity decreased risk of further relapse when at least 2 new T2L had occurred. This study provides Class III evidence that clinically stable patients with MS on low-/moderate-efficacy DMT with ≥3 new T2L on MRI who escalate DMT have a reduced risk of relapse and Expanded Disability Status Scale progression.

Late-Onset Neuromyelitis Optica Spectrum Disorder Mimicking a Non-Arteritic Anterior Ischemic Optic Neuropathy-Case Report.

A 60-year-old white woman presented to the emergency department with painless decrease of visual acuity in the left eye (LE). The diagnosis of a non-arteritic anterior ischemic optic neuropathy in the LE was established based on the clinical picture and the results of static perimetry, fluorescein angiography, visual evoked potential, and magnetic resonance imaging (MRI) of the brain and orbit. Six months later, the patient reported visual impairment in the right eye (RE). Best corrected visual acuity (BCVA) in the RE was 5/10. Gadolinium-enhanced MRI showing inflammation of both optic nerves and the optic chiasm in correlation with positivity for immunglobulin G antibody against aquaporin-4 led to the diagnosis of late-onset neuromyelitis optica spectrum disorder. High-dose intravenous methylprednisolone therapy followed by oral tapering was administered and oral azathioprine was started to reduce the risk of further relapse. At discharge, BCVA was 5/5 in the RE. The patient remains under the care of neurology and ophthalmology clinics, with no recurrences for two years. The possibility of neuromyelitis optica spectrum disorder with optic neuritis in older patients is important in the differential diagnosis of ischemic optic neuropathy.

Exercise therapy during hospitalization for a pediatric patient with active IgA nephropathy: A case report

Exercise therapy for pediatric patients with active IgA nephropathy is necessary to improve physical mobility functioning and maintaining a normal daily and school-life, whilst managing the risk of further relapse; although, this has not been investigated yet. This case report aimed to evaluate the influence of exercise therapy in a pediatric patient with active IgA nephropathy whilst being treated in-hospital with a multiple-drug combination therapy. The patient was an 18-year-old girl diagnosed with IgA nephropathy a year prior to her admission at the hospital for multiple-drug combination therapy. Moderate-intensity exercise therapy was started on the 8th day and continued until the 31st day, at discharge. The results of her physical functioning on the 8th and 30th day were grip strength from 21.1 kg to 21.0 kg, knee extension strength from 0.59 kgf/kg to 0.74 kgf/kg, skeletal muscle mass index from 7.2 kg/m2 to 6.7 kg/m2, 6-minute walk test from 570 m to 590 m, and peak work rate from 100 watts to 110 watts. Muscle strength and exercise tolerance were maintained, or improved. The urine protein/creatinine ratio (UP/Cr) from the 8th day to discharge decreased from 0.4 g/gCr to 0.2 g/gCr. There was no recurrence of IgA nephropathy during hospitalization. Exercise therapy during hospitalization in a pediatric patient with active IgA nephropathy may not have adverse effects, and may prevent a decline in physical function and exercise tolerance.

FC067: Long-Term Outcome of Childhood Onset Idiopathic Nephrotic Syndrome

Abstract BACKGROUND AND AIMS Little is known about the long-term outcome during adulthood of childhood onset idiopathic nephrotic syndrome (INS). We aimed to determine which patients require long-term follow up after transition, to identify risk factors of relapse and to analyze treatment strategies. METHOD In this monocentric retrospective study, we included all patients admitted in our adult nephrology department with INS diagnosed during childhood. Patients who reached kidney failure during childhood were excluded. Data regarding the outcome at adult age were obtained through clinical database and medical charts. RESULTS Eighty-two patients (male/female = 2/1) were included, with a median age at diagnosis of 3.9 years (1.2–16.5). Sixty-eight patients had steroid-sensitive INS, including 52 with steroid-dependent nephrotic syndrome or frequently relapsing nephrotic syndrome. Fourteen patients had steroid-resistant nephrotic syndrome. A total of 89% of patients received corticosteroid sparing treatment during childhood. Median follow-up during adulthood was 6.2 (0.3–25) years. A total of 71% of patients experienced at least one relapse during adulthood. The total number of relapses during childhood and the number of relapses per year during childhood, reflecting disease activity, were significantly higher in patients who experienced relapses during adulthood than in patients who did not (Figure 1). The risk of relapse during adulthood was also significantly associated with the need for immunosuppressive regimen at the time of the transition visit (P = 0.002). To promote the successful transition of young people, we propose to organize a transition visit where the adolescent/young adult is seen jointly by pediatric and adult nephrologists, as it was done for 68% of patients in this study. The relapse rate was significantly lower (50%) in the subgroup of patients who had such a transition visit. We also found that relapse during the first two-years of adulthood follow-up was significantly associated with the risk of further relapse, highlighting the need for a close follow-up during the transition period. A total of 45% of patients received corticosteroid sparing treatment during adulthood, mainly mycophenolate mofetil (N = 23), calcineurin inhibitors (N = 21) and rituximab (N = 12). The main complications were high blood pressure (20/82, 26%) and osteopenia (19/26, 73% when bone densitometry was performed). Only one thrombo-embolic event and three severe infections were reported. At last follow-up, median eGFR was 87.1 (23.4–150.8) mL/min/1.73 m². CONCLUSION The incidence of relapses in adulthood is high in patients with active disease during childhood. A long-term follow-up is mandatory in these patients. Whereas renal function remained normal in most patients, high blood pressure and osteopenia were frequent and should be carefully monitored during adulthood. Transition visit should be carefully coordinated to prevent the risk of nonadherence.

Recent advances in testicular germ cell tumours.

Testicular germ cell tumours (TGCTs) are the most common solid tumours in young men and have an excellent overall cure rate and prognosis. In most patients, localised disease is cured by surgery alone, and a minority of patients receive short-course adjuvant chemotherapy to reduce the risk of further relapse. Also, in about 80% of patients, metastatic disease can be cured by systemic cisplatin-based chemotherapy. Unfortunately, for a proportion of patients, the disease exhibits platinum resistance and relapse occurs. Despite further lines of systemic treatment, cure can be difficult to achieve in these patients and ultimately about 20% of them will die from disease progression. Addressing the mechanisms underpinning platinum resistance is critical to improving the survival and chances of cure for these patients. This review describes the latest advances in TGCT research, focusing on the identification of novel biomarkers, genetic characteristics and exploring novel treatments.

Usefulness of MOG-antibody titres at first episode to predict the future clinical course in adults.

To analyze whether myelin oligodendrocyte glycoprotein antibody (MOG-Ab) titres at onset of the disease were different according to the clinical phenotype at presentation, and to investigate whether the titres were associated with risk of further relapses or predicted clinical outcome in adult patients. Finally, we assessed an alternative method to the classical measurement of MOG-Ab levels by serial dilutions. This is a retrospective study including 79 MOG-Ab-positive adult patients, whose samples were obtained at first episode. MOG-Ab were tested by cell-based assay. HEK293 cells were transfected (tHEK293) with human-MOG plasmid. Non-tHEK293 cells were used as negative controls. Assessment of antibody titres was performed by serial dilution, and delta mean fluorescence intensity ratio signal (MOG-ratio ΔMFI) by flow cytometry. MOG-ratio ΔMFI was calculated as follows: (MFI tHEK293cells- MFI non-tHEK293cells)/MFI non-tHEK293cells. MOG-ratio ΔMFI was calculated from the first serum dilution at 1:320. The association between MOG-Ab titres and risk of relapse was analyzed by Cox regression. The association between MOG-Ab titres and visual or motor disability at last follow-up was performed by binary logistic regression. Poor visual outcome was defined when patients displayed some degree of visual disability (visual acuity [VA] < 20/20) and poor motor outcome when patients displayed some degree of motor disability (Disability Status Scale [DSS] > 1). We also investigated correlations between MOG-Ab titres and MOG-ratio ΔMFI. MOG-Ab titres were higher in Caucasians than in those with other ethnicities, and in patients with a more severe VA (VA ≤ 20/100) or motor disability (DSS ≥ 3.0) at onset (p = 0.006, 0.034, and 0.058, respectively). MOG-Ab titres were not associated with risk of relapses or with the final clinical outcome. MOG-ratio ΔMFI correlated with MOG-Ab titres in the whole cohort (ρ = 0.90; p < 0.001), and when stratified by initial clinical phenotype. High MOG-Ab titres at onset are associated with a more severe presentation, but do not predict the future disease course. MOG-ratio ΔMFI is an alternative and straightforward method to determine MOG-Ab levels.

Vinorelbine-based chemo-radiotherapy in non-small cell lung cancer.

Concomitant radio-chemotherapy improves survival of patients with locally advanced non-small cell lung cancer, with a better local-regional control. We report our experience with vinorelbine-based chemotherapy in neoadjuvant and radical settings in 43 patients. Regimens consisted of cisplatin plus vinorelbine in 74.4% patients and carboplatin plus vinorelbine in 14.0%; 11.6% underwent mono-chemotherapy with oral vinorelbine. We estimated the crude probability of death or local recurrence by the Kaplan-Meier method. Cox regression models were used to identify the main significant predictors of death or local recurrence. A significant effect of the response to treatment was shown on both local disease free-survival (P = 0.004) and overall survival (P <0.0001). Patients with progressive disease after primary treatment had a significantly higher risk of further relapse at both univariate (P = 0.046) and multivariate regression analysis (P = 0.014) than patients with a complete response. They also showed a significantly higher risk of death at both univariate (P = 0.0005) and multivariate regression analysis (P <0.0001) than patients with a complete response. The most common toxicity was hematologic and gastroenteric. We recorded grade III/IV leukopenia in 11%, anemia in 6%, and esophagitis in 14% of the patients. Our experience showed that vinorelbine-based chemotherapy is an effective and safe regimen, in association with a platinum compound and thoracic radiotherapy.

Predictors for readmission within one year after discharge from an alcohol rehabilitation program

IntroductionAlcohol use disorders have been associated with an increased risk of frequent readmissions. This study aimed to examine factors that contribute to the risk for readmission within one year after discharge from an alcohol rehabilitation program.MethodsRehospitalization status was assessed for all patients with an alcohol use disorder as primary diagnosis (n = 468) admitted to our inpatient unit between July 1, 2012, and June 30, 2014. All patients were followed up for one year after their first hospitalization (index hospitalization) within this period. Time to readmission within one year after discharge was measured using the Kaplan–Meier method. Risk factors for readmission were examined using Cox proportional hazard regression models. Three set of variables were selected to be included in the analyses:– demographic features at time of admission of index hospitalization;– comorbid conditions at time of admission of index hospitalization;– treatment-related variables in relation to the index hospitalization including observer-rated outcome measures.ResultsReadmissions within one year after discharge from an alcohol rehabilitation program as well as the corresponding time to readmission were linked to higher numbers of previous hospitalizations and the presence of comorbid opioid use disorders.ConclusionHigher numbers of past treatments for AUD are indicators for a chronic course of the disorder, which, in turn, increase the risk of further relapses. Our findings further confirmed previous findings suggesting high rates of comorbidity among alcohol and opioid use disorders, and their link with poorer clinical outcomes.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Current Treatment of Locoregional Recurrence of Melanoma

Surgical resection is the mainstay of therapy for locoregional recurrence of melanoma and the best chance for long-term cure in patients with locoregional recurrence of melanoma. In addition to true local recurrence at the site of the primary lesion, locoregional relapse can occur as regional nodal disease or as satellite or in-transit metastases, which may be unresectable and can present significant treatment challenges. Options for unresectable locoregional recurrence include regional hyperthermic isolated limb perfusion or isolated limb infusion, topical therapies, intralesional injection therapies, laser ablation, radiation therapy, and systemic therapy. Given the risk of further relapse and the negative impact on prognosis and overall survival after locoregional recurrence of melanoma, most patients should be considered for aggressive locoregional therapy.

Vinorelbine-Based Chemo-Radiotherapy in Non-Small Cell Lung Cancer

Concomitant radio-chemotherapy improves survival of patients with locally advanced non-small cell lung cancer, with a better local-regional control. We report our experience with vinorelbine-based chemotherapy in neoadjuvant and radical settings in 43 patients. Regimens consisted of cisplatin plus vinorelbine in 74.4% patients and carboplatin plus vinorelbine in 14.0%; 11.6% underwent mono-chemotherapy with oral vinorelbine. We estimated the crude probability of death or local recurrence by the Kaplan-Meier method. Cox regression models were used to identify the main significant predictors of death or local recurrence. A significant effect of the response to treatment was shown on both local disease free-survival (P = 0.004) and overall survival (P <0.0001). Patients with progressive disease after primary treatment had a significantly higher risk of further relapse at both univariate (P = 0.046) and multivariate regression analysis (P = 0.014) than patients with a complete response. They also showed a significantly higher risk of death at both univariate (P = 0.0005) and multivariate regression analysis (P <0.0001) than patients with a complete response. The most common toxicity was hematologic and gastroenteric. We recorded grade III/IV leukopenia in 11%, anemia in 6%, and esophagitis in 14% of the patients. Our experience showed that vinorelbine-based chemotherapy is an effective and safe regimen, in association with a platinum compound and thoracic radiotherapy.

18F-FDG PET to identify soft tissue disease in multiple myeloma

Multiple myeloma is the second commonest haematological malignancy and identification of sites and extent of disease is vital for diagnosis, planning and prognosis [1]. Most lesions are osseous and readily identifiable on X-ray. Extramedullary myeloma is much less common and extramedullary lesions cannot be detected on X-ray. Although MRI may assist in identification of sites of disease it cannot separate active versus nonactive disease [2]. F-Fluorodeoxyglucose (FDG) positron emission tomography (PET), as in this case, can identify in one easy scanning procedure all sites of disease [3, 4], both osseous and extraosseous. A 52-year-old man was diagnosed with IgD kappa multiple myeloma 4 years ago, presenting with bone disease only. Following two bone relapses (treated with multiple chemotherapies, radiotherapy and autologous peripheral blood stem cell transplant) he underwent a reduced intensity allogeneic stem cell transplant from his brother. Due to the high risk of further relapse, 5 months later an F-FDG PET/CT scan (A) was performed for routine evaluation of disease. This showed no evidence of active disease. Seven months later he presented with a soft tissue nodule near his right knee. Biopsy showed a myeloma deposit. A further F-FDG PET/CT scan (B) was arranged for staging. This showed multiple soft tissue/subcutaneous FDG-avid nodules [arrows (a)] as well as bone disease [arrows (b)].

Management of breakthrough disease in patients with multiple sclerosis: when an increasing of Interferon beta dose should be effective?

BackgroundIn daily clinical setting, some patients affected by relapsing-remitting Multiple Sclerosis (RRMS) are switched from the low-dose to the high-dose Interferon beta (IFNB) in order to achieve a better control of the disease.PurposeIn this observational, post-marketing study we reported the 2-year clinical outcomes of patients switched to the high-dose IFNB; we also evaluated whether different criteria adopted to switch patients had an influence on the clinical outcomes.MethodsPatients affected by RRMS and switched from the low-dose to the high-dose IFNB due to the occurrence of relapses, or contrast-enhancing lesions (CELs) as detected by yearly scheduled MRI scans, were followed for two years. Expanded Disability Status Scale (EDSS) scores, as well as clinical relapses, were evaluated during the follow-up period.ResultsWe identified 121 patients switched to the high-dose IFNB. One hundred patients increased the IFNB dose because of the occurrence of one or more relapses, and 21 because of the presence of one or more CELs, even in absence of clinical relapses. At the end of the 2-year follow-up, 72 (59.5%) patients had a relapse, and 51 (42.1%) reached a sustained progression on EDSS score. Overall, 85 (70.3%) patients showed some clinical disease activity (i.e. relapses or disability progression) after the switch.Relapse risk after increasing the IFNB dose was greater in patients who switched because of relapses than those switched only for MRI activity (HR: 5.55, p = 0.001). A high EDSS score (HR: 1.77, p < 0.001) and the combination of clinical and MRI activity at switch raised the risk of sustained disability progression after increasing the IFNB dose (HR: 2.14, p = 0.01).ConclusionIn the majority of MS patients, switching from the low-dose to the high-dose IFNB did not reduce the risk of further relapses or increased disability in the 2-year follow period.Although we observed that patients who switched only on the basis on MRI activity (even in absence of clinical attacks) had a lower risk of further relapses, larger studies are warranted before to recommend a switch algorithm based on MRI findings.

Viscum album fermentatum Pini versus oral etoposide as adjuvant treatment in osteosarcoma patients after second relapse.

TPS331 Background: Patients with localized osteosarcoma can be cured in approximately 60% of cases with neoadjuvant chemotherapy, only few experimental drugs are available for relapsed and inoperable patients. We know from historical controls that after the second relapse the risk of further relapses increases. The 12-months disease-free survival (DFS) after the second relapse is about 12% in our historical controls (Fagioli F2002, Bacci G 2005). Oral etoposide is often used in clinical practice due to some evidence of effectiveness when administered iv as second-line treatment. Viscum fermented mistletoe extract (Viscum Loranthaceae) is a phytocompound popular in cancer treatment across central Europe with immunomodulatory activity. Encouraged by the preliminary findings in 4/5 osteosarcoma patients treated with Viscum: who experienced a DFS > 12 months after their second relapse, we designed a phase II study randomized, prospective study. Methods: In June 2007 after approval by ethic committee a phase II, prospective, two-arm, randomized clinical study started comparing Viscum album fermentatum Pini ( s.c., 3 times/wk) for 1 year versus etoposide (50 mg/m2 orally, day 1-21, every 28 days for 6 cycles) in patients with diagnosis of high-grade osteosarcoma free from disease after second relapse, with age > 10 yrs, ECOG performance status 0-2, no other concomitant antitumoral treatment, no other past or present malignancies, normal renal, hepatic, and bone marrow function. Principal endpoint: 1 yr DFS of 40% in one of the two arm compared to a historical group (12%). Secondary end points are quality of life according to EORTC QLQ-C30 and evaluation of immune modulation measured by Natural Killer lymphocytes T,IL2, IL12, IL15, gamma IFN, and IP10. To date we have enrolled 13 pts, 6 in the Viscum arm and 7 in the etoposide arm. Median follow-up time is 15 months (5-30) while the study is in progress. Accrual is still open to at least 20 patients. Preliminary data are reported about toxicity and DFS. No significant financial relationships to disclose.

Efficacy and safety of fluticasone propionate 0.005% ointment in the long‐term maintenance treatment of children with atopic dermatitis: Differences between boys and girls?

Treatment of atopic dermatitis (AD) in children tends to stabilize the condition in the short term. 'Maintenance' treatment options in children are limited. To assess the efficacy and safety of twice daily treatment with fluticasone propionate 0.005% (FP) ointment during 4 wk and the efficacy and safety of twice weekly maintenance treatment with FP in preventing exacerbations or remissions of AD during a 16 wk follow-up period. Ninety children (aged 4-10 yr) with moderate to severe AD were included in a randomized, multi-centre study and received FP ointment twice daily during the acute phase. Children whose AD was in remission after 4 wk of treatment, entered the maintenance phase. In addition to twice daily emollient, children were randomly allocated to receive FP or placebo ointment twice weekly on consecutive days. Efficacy was assessed by the objective SCORAD. Eighty-seven (97%) completed the 4-wk acute study period. Extensive remission was achieved in 78 (87%) children, and 75 children entered the maintenance phase. Intermittent treatment with FP resulted in less severe AD and significantly reduced risk of further relapse as compared with placebo. The risk of an exacerbation of AD was more than twice as high in the placebo group as in the FP group (hazard ratio 2.182, 95% CI). AD in girls was better controlled than in boys. This long-term study shows that the addition of twice weekly FP to standard maintenance therapy significantly reduces the risk of relapse in children with moderate severe AD.

A biopsychosocial model as a guide for psychoeducation and treatment of depression

Effective treatment of severe or chronic unipolar depression requires the combination of pharmacological and psychotherapeutic interventions, and demands a theoretical paradigm integrating biological and psychosocial aspects of depression. Supported by recent research, we propose in our article a biopsychosocial diathesis-stress model of depression. Its basic aim is psychoeducational: to provide therapists, patients, and their environment a constructive conceptual framework to understand depressive complaints, vulnerability, and stress. The core of the model consists of the concept of psychobiological vulnerability, which is determined by risk factors-of a biogenetic, psychological, somatic, and societal nature-and by protective factors. Life events with an idiosyncratic, stress-inducing value interact with this vulnerability, triggering severe or chronic distress that affects the individual's resilience and leads to symptoms of depression. The pathogenesis of depression is symbolized by a negative downward loop, in which interactions among symptoms, vulnerability, and stressors drive the patient toward a depressive condition. Moreover, experiencing recurrent depression influences psychobiological vulnerability, the occurrence of stressors, and tremendously increases the risk of further relapse. The model stresses the self-evident integration of biological and psychological therapeutic interventions that need to focus on symptom reduction and on relapse prevention. Moreover, it offers the patient and therapist a psychoeducational context in which the individual's vulnerability and depressive symptoms can be treated. Finally, applications of the depression model as a therapeutic approach to severe depression in the phases of remoralization, symptom reduction, and relapse prevention are presented.

Neutron radiotherapy for recurrent pleomorphic adenomas of major salivary glands.

Pleomorphic adenoma is the most common neoplasm arising in the salivary glands. Surgical management is the primary therapeutic modality. With the use of modern surgical techniques, recurrence is infrequent, and facial nerve sparing is the norm. However, for patients with recurrent disease, the risk of further relapses is increased with surgical resection alone, particularly for those patients in whom multiple recurrences have already occurred. The role of adjuvant radiotherapy in this setting remains uncertain. Although neutron radiotherapy is superior to conventional radiotherapy for malignant salivary gland tumors, its role in the treatment of pleomorphic adenomas is less well defined. We report our experience using this modality for high-risk, recurrent pleomorphic adenomas. Sixteen patients were treated with neutron radiotherapy for recurrent pleomorphic adenomas of major salivary glands from 1986 through 1993. The median age at diagnosis was 33 years (range, 11-77 years); median age at the time of neutron radiotherapy was 52 years (range, 22-77 years); median number of prior surgical procedures was 3 (range, 1-6); median duration from initial diagnosis to radiotherapy was 14.5 years (range, 3 months-30 years); median follow-up was 83 months (range, 9-144 months). The median period at risk for survivors was 96 months (defined as the interval from completion of neutron radiotherapy to last follow-up). Ten patients had evidence of gross residual disease at the time of treatment as determined by imaging studies, with nine patients having multinodular disease. The 10-year actuarial survival was 79%. One patient died from lung metastases 9 months after treatment; one patient died from a liver tumor of uncertain origin, but the histology could not rule out a metastasis from the previous pleomorphic adenoma; and one patient died from recurrent disease at the base of skull. The 15-year actuarial locoregional control rate was 85%. One of the two patients with locoregional recurrence had a malignant transformation into an adenocarcinoma. No statistical difference in 15-year actuarial survival (75% vs 83%, p =.82) was found comparing patients with gross residual disease vs microscopic residual disease. The actuarial 15-year locoregional control was 76% for patients with gross residual disease vs 100% for those with microscopic disease. The 15-year actuarial risk of RTOG/ESTRO nonaudiologic grade III/IV complications was 21%. No facial nerve injuries were observed as a direct consequence of neutron radiotherapy. Neutron radiotherapy offers both excellent local control rates and survival rates in patients with multiply recurrent pleomorphic adenomas that are not candidates for surgical resection, even in the presence of gross residual disease. The treatment-related morbidity is acceptable. Malignant transformations and metastases, although uncommon, may be observed in this tumor.

An analysis of the treatment of 114 patients with recurrent pleomorphic adenomas of the parotid gland

Nerve preserving surgery is widely recommended for recurrent parotid pleomorphic adenomas though the risk of further relapse may be high. Adjuvant radiotherapy may improve control but its exact role requires clarification. A series of 114 patients with first recurrences treated between 1952 and 1992 is reviewed. Treatment modality was either surgery alone (SG; n = 63) or surgery with radiotherapy (SG + RT; n = 51). Results were determined with respect to long-term tumor control (K-M life-tables) and facial nerve function. The rate to second recurrence was 15% (17/114), median follow-up 14 years. There were no cases of malignant degeneration. Multinodular recurrences treated by SG were at particular high risk of relapse, but control was significantly improved with adjuvant radiotherapy (SG versus SG = RT; 43% versus 4% at 15 years, P = 0.008). In contrast, no difference was demonstrated in the uninodular tumor group (SG versus SG = RT; 15% versus 13% at 15 years, P = 0.9). The incidence of permanent facial nerve injury was 15%. This study emphasizes the distinction between multinodular and uninodular recurrences; the former is at high risk of relapse and benefits from adjuvant radiotherapy whereas solitary tumors may be adequately treated by surgery alone.

Prognosis following salvage mastectomy for recurrence in the breast after conservative surgery and radiation therapy for early-stage breast cancer.

The prognosis and factors that influence prognosis following salvage mastectomy in patients with recurrence in the treated breast after conservative surgery (CS) and radiation therapy (RT) were investigated. A total of 1,593 patients with stage I or II invasive breast cancer were treated following gross total excision of the tumor at the Joint Center for Radiation Therapy (JCRT) between 1968 and 1985. One hundred sixty-six of the 1,593 (10%) had subsequent recurrence in the breast. Of these, 123 had salvage mastectomy and constitute the study population. The recurrent tumor was predominantly invasive in 99 patients, noninvasive in 14, and focally invasive in 10. Following mastectomy, chemotherapy or hormonal therapy was administered to 29 patients. The median follow-up time was 39 months after salvage mastectomy. The 5-year actuarial rate of further local or distant relapse for the entire group was 41%. None of the 24 patients with focally invasive or noninvasive tumors had a subsequent relapse. In comparison, the 5-year actuarial rate of further relapse in the 99 patients with a predominantly invasive recurrence was 52% (P = .001). The method of detection of the recurrence, the age of the patient at initial diagnosis, the disease-free interval, and the location of the recurrence in the breast were not found to have a statistically significant association with the risk of further relapse. We conclude that the histology of the recurrent tumor is an important prognostic factor for the risk of further relapse. Patients with purely noninvasive or focally invasive tumors have an excellent prognosis following salvage mastectomy. In contrast, patients with predominantly invasive tumors are at substantial risk for further relapse.

Studies on the Course of Recurrent Endogenous Affective Disorders

Comparison of rates of relapse before lithium administration and after double-blind and open discontinuation has shown (a) that the course of severe endogenous affective disorders is not easily influenced by the attitude of the doctor or the patient, and (b) that there is a high risk of further relapses in a group of patients who have had 2 or more episodes within a period of 2 years.