Paraneoplastic syndrome in lung cancer.

AIM: To study the nature of different variants of paraneoplastic syndrome (PNPS) in lung cancer, taking into account the features of the tumorous process and the complications of radiochemotherapy. PATIENTS AND METHODS: We performed an analysis of the data of 1,669 patients with lung cancer aged between 24 and 87 years, among whom there were 89% of men and 11% of women. The ratio of small cell and non-small-cell histological variants of the lung cancer was 1: 4, IB, IIA, IIB, IIIA, IIIB and IV stages of cancer - 1:2:6:58:43:57. RESULTS: PNPS developed in 16% of the lung cancer patients, in these patients we have detected a marked increase in the disease incidence in women, the peripheral form of the tumor, the apical variant of Pancoast - Tobias and adenocarcinoma, but no cases of the median lower localization of the tumor. The number of the upper lobar pathology was decreased, while the severity of the cancer was significantly greater, which more often occurred with exudative pleurisy, germination of the tumor into the chest wall and compression of the upper vena cava. The 21 components of PNPS pathology were established. We distributed them conditionally into the musculoskeletal system lesions, variants of skin vasculitis and autoimmune processes, the nature of which depended on the localization and course of the tumorous process, its histological variation and severity of the course. Moreover, PNPS negatively affected the development of radiochemotherapy complications and worsened survival rate. CONCLUSIONS: The course of PNPS in lung cancer is highly diverse, being a risk factor for a severe tumorous process that worsens the survival of patients.

Chronic Intestinal Pseudo-obstruction and Orthostatic Hypotension Associated with Small Cell Lung Cancer that Improved with Tumor Reduction after Chemoradiotherapy.

Chronic intestinal pseudo-obstruction (CIPO) is a rare disease with symptoms of ileus without obstruction. Most cases of CIPO are idiopathic, and CIPO as a paraneoplastic neurological syndrome (PNS) associated with small cell lung cancer (SCLC) is rare. A 63-year-old man was diagnosed with functional ileus and confined to bed due to orthostatic hypotension. Chest computed tomography revealed a right hilar mass suspected of being lung cancer. Based on detailed examinations, he was diagnosed with limited-stage SCLC. His symptoms were confirmed as PNS because his serum anti-Hu antibody was positive. His PNS was improved with complete tumor reduction by chemoradiotherapy.

Successful treatment of tumor-induced osteomalacia due to an intracranial tumor by fractionated stereotactic radiotherapy.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome, characterized by tumor secretion of fibroblast growth factor-23 (FGF23) causing hypophosphatemia due to renal phosphate wasting. TIO is usually caused by small, benign, difficult-to-localize, mesenchymal tumors. Although surgery with wide excision of tumor borders is considered the "gold standard" for definitive therapy, it can be associated with considerable morbidity depending on the location. To date, radiation therapy has not been considered as an effective treatment modality in TIO. OBJECTIVE: A 67-year-old female presented with multiple nontraumatic fractures, progressive bone pain, and muscle weakness for 4 years. She was found to have biochemical evidence of urinary phosphate wasting with low serum phosphorus, low-normal serum calcium, normal 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and high serum FGF23 levels. TIO was diagnosed. Selective venous sampling for FGF23 confirmed that a 1.7-cm left frontal mass, radiographically similar to a meningioma, was the causative tumor. She declined surgery due to fear of complications and instead underwent fractionated stereotactic radiotherapy for 6 weeks. RESULTS: In less than 4 years after radiation therapy, she was successfully weaned off phosphorus and calcitriol, starting from 2 g of oral phosphorus daily and 1 µg of calcitriol daily. Her symptoms have resolved, and she has not had any new fractures. CONCLUSIONS: Stereotactic radiotherapy was an effective treatment modality for TIO in our patient. Fractionated stereotactic radiation therapy represents an alternative to surgery for patients with TIO who are not surgical candidates or who decline surgery.

Radiotherapy of splenomegaly : a palliative treatment option for a benign phenomenon in malignant diseases.

PURPOSE: Since the 20(th) century, radiotherapy (RT) has been used for treatment of symptomatic splenomegaly (SM). SM occurs in association with hematologic disorders. The purpose of this analysis was to determine the indication, treatment concepts, and efficiency of RT. MATERIAL AND METHODS: Clinical features, treatment concepts, and outcome data during the past 20 years were analyzed. Endpoints were pain relief, symptomatic and hematological response, and treatment-related side effects. RESULTS: From 1989-2009, a total of 122 patients received 246 RT courses because of symptomatic SM. Overall 31 patients had chronic myelogenous leukemia (CML), 37 had chronic lymphocytic leukemia (CLL), 23 had osteomyelofibrosis (OMF), 17 had polycythemia vera (PV), 5 had acute myelogenous leukemia, 4 had idiopathic thrombocytopenic purpura (ITP), 3 had non-Hodgkin lymphoma (NHL), and 2 had multiple myeloma (MM). Patients were treated with (60)Co gamma rays or 5-15MV photons. The fraction size ranged from 10-200 cGy and the total dose per treatment course from 30-1600 cGy. Significant pain relief was achieved for 74.8% of the RT courses given for splenic pain. At least 50% regression was attained for 77% of the RT courses given for SM. 36 patients died within 2 months due to the terminal nature of their disease. Of the RT courses applied for cytopenia, 73.6% achieved a significant improvement of hematological parameters and reduction of transfusion need. Notable hematologic toxicities were reported < EORTC/RTOG II°. CONCLUSION: The present analysis documents the efficacy of RT. In addition, RT as a palliative treatment option for symptomatic SM should not be forgotten.

A case of cervical cancer-related membranous nephropathy treated with radiation therapy.

Paraneoplastic nephropathy is a rare complication of malignant disease. We present a case of cervical cancer with biopsy-proven membranous nephropathy and associated nephrotic syndrome. Irradiation to the specific neoplasm site and to the metastatic paraaortic lymph node tissues lead to regression of the nephrotic syndrome without causing severe adverse events. Radiation therapy can be the first choice in the treatment of paraneoplastic nephrotic syndrome if the primary neoplasm is unresectable. Invasiveness of intervention and patient prognosis should be carefully deliberated in the management of the two diseases.

Neoplastic meningitis from systemic malignancies: diagnosis, prognosis and treatment.

Long-term survival is occasionally observed in patients with neoplastic meningitis (NM) accompanying breast cancer (13% one-year and 6% 2-year survival), melanoma, and lymphoma, but in general the survival of most patients is short and averages only 3 to 4 months. The incidence of NM appears to be increasing, in part due to earlier detection by magnetic resonance imaging (MRI), and in part due to development of more effective therapies for systemic cancer, which has resulted in a larger subset at risk for late-stage development of this complication. Survival of NM patients is negatively affected by concomitant progression of systemic disease despite multiple prior therapies. However, there are certain prognostic factors that have been identified as "favorable" in retrospective series, including age less than 60 years, long symptom duration, controlled systemic disease, Karnofsky performance status (KPS) > or =70, lack of encephalopathy or cranial nerve deficits, low initial cerebrospinal fluid (CSF) protein level, history of breast primary tumor, and lack of evidence of CSF compartmentalization or bulky meningeal disease as determined by CSF flow studies. Standard treatment has traditionally involved radiotherapy (RT) to sites of symptomatic or bulky disease, as detected by neuroimaging, and in selected patients, the administration of intrathecal, intraventricular, or systemic chemotherapy. However, treatment remains palliative and many patients and physicians choose supportive care only. Future hope is provided by studies that have improved our understanding of the disease pathogenesis, have identified prognostic variables associated with outcome, and have provided new therapeutic approaches, such as administration of high-dose systemic chemotherapy and investigations of novel therapeutic agents.

Primitive neuroectodermal tumor arising in long-standing cerebellar atrophy.

Primitive neuroectodermal tumors (PNETs) account for one fifth of childhood brain tumors. Although little is known of the pathobiology of this tumor type, there are associations with both genetic syndromes and exposures to specific environmental agents. Progressive cerebellar atrophy predating the presentation of a primary brain tumor, in the absence of a genetic syndrome, has not been reported with PNETs. We report a case of a posterior fossa PNET occurring in association with long-standing cerebellar atrophy without evidence of a genetic syndrome. This case may represent an unrecognized paraneoplastic syndrome or a unique subtype of PNET.

Bazex syndrome.

Bazex syndrome is a paraneoplastic acrokeratosis appearing mostly at the same time as the underlying neoplasm. We report a typical case with a squamous cell carcinoma of the tongue and classical cutaneous symptoms disappearing with the treatment of the tumour.

Effectiveness of radiation therapy in nephrotic syndrome associated with advanced lung cancer.

Paraneoplastic nephrotic syndrome is rare, bur occurs mostly in lung cancer. The glomerular lesion usually exhibits membranous nephropathy. Although surgical therapy has been shown to be effective, the treatment of a paraneoplastic nephrotic syndrome has always been a challenge. Currently no standard therapy has been established, if the paraneoplastic nephrotic syndrome is associated with advanced cancer with unresectable lesions. We present 2 cases having paraneoplastic nephrotic syndrome associated with advanced squamous cell carcinoma of the lung. Radiation therapy of the primary tumor effectively caused regression of the paraneoplastic nephrotic syndrome without affecting the renal function. Our results suggest that irradiation can be the first choice in the treatment of nephrotic syndrome, if the primary tumor is unresectable.

A review of the therapy of paraneoplastic neurologic syndromes.

The therapy of paraneoplastic neurologic syndromes remains unclear and warrants a systematic review of the literature. Reports in English and foreign language literature were abstracted. Data were sorted by the primary paraneoplastic neurologic syndrome, the primary malignancy, and the methods of treatment. Neurologic improvement follows surgical, chemotherapeutic, and radiation treatments. Adjuvant immunosuppressive therapy with steroids, plasmapheresis, or immunoglobulin may help stabilize the progression of neurologic symptoms. Syndromes characterized by inflammation or neurotransmitter production without neuronal loss are most responsive to therapy. While treatment of the underlying cancer with appropriate surgery, chemotherapy, and radiation is recommended, the paraneoplastic syndrome should probably be managed with immunosuppressive therapy.

[Predictive significance of reflex otalgia in local radical radiotherapy of oropharyngeal carcinomas]. / Prädiktive Bedeutung der Reflexotalgie in der lokal radikalen Radiotherapie von Oropharynxkarzinomen.

BACKGROUND: Patients with carcinomas of the upper aero-digestive tract often suffer from ear pain as a tumor associated syndrome. This prospective study examines the predictive and prognostic value of this symptom. PATIENTS AND METHODS: Ninety-six consecutive patients who completed a locally radiotherapy of a carcinoma of the oropharynx were prospectively evaluated and followed. Forty-nine out of 96 patients stated the symptom, either spontaneously or after questioning. The 2 groups showed no difference regarding TNM-classification, histology and total dose. Overall survival, local control and disease specific survival were calculated according to Kaplan-Meier and compared by the log-rank test. RESULTS: A clinically complete remission was obtained in significantly fewer patients with reflex-otalgia as compared to patients without reflex-otalgia, 61.2% versus 89.3%, p < 0.002. Local control of patients with reflex-otalgia was significantly less with 49%, mean follow-up 564 days, in comparison to local control in patients without reflex-otalgia, mean follow-up 613 days, p = 0.01. Disease specific survival was significantly worse for patients with reflex-otalgia, p < 0.012. The probability of local control of T1/T2 tumors with reflex-otalgia was similar to T3/T4 tumors without reflex-otalgia. Local control for all tumor categories combined is 74% for patients without reflex-otalgia versus 49% for patients with reflex-otalgia. CONCLUSION: In our patients, reflex-otalgia is a new and statistically significant parameter for the probability of local control and disease specific survival.

[Paraneoplastic IgA nephritis as the initial symptom of bronchial carcinoma]. / Paraneoplastische IgA-Nephritis als Erstsymptom eines Bronchialkarzinoms.

We report on a 45-year old patient who was treated for IgA-Nephritis for 9 months. During treatment he developed coughing and dyspnoea which led to diagnose a central stenosing NSCLC at the tracheobronchial angle. Cancer treatment by x-ray showed a good response, e.g. significant reduction of cancer volume and a remarkably improved renal function. In the course of tumour progression (3 months after initial treatment) retention parameter deteriorated again and the patient needed to be dialysed. Palliative laser therapy had no influence on renal function. The close linkage between tumour regression and the extent of IgA nephritis suggest that the preceding IgA nephritis was paraneoplastic and hence a primary symptom of the NSCLC.

Paraneoplastic cerebellar degeneration in association with Hodgkin's disease: a report of two cases.

Two patients with paraneoplastic cerebellar degeneration accompanying Hodgkin's disease were treated with plasma exchange in combination with chemotherapy or radiation therapy, respectively. Significant improvement in neurologic symptoms was obtained in 1 of them.

Optic neuropathy: a rare paraneoplastic syndrome.

A 63-year-old man developed gradually progressive bilateral loss of vision, cerebellar ataxia, and downbeat nystagmus. Visual acuity was 20/400 OD and 20/200 OS, with cecocentral scotomas OU. Fundus examination showed bilateral optic atrophy and a vitreous cellular reaction. MRI of the brain was normal. CSF protein was elevated, with increased IgG levels but no malignant cells. Biopsy of a pulmonary lymph node showed undifferentiated small cell carcinoma. Neoplastic cells were positive for neuron-specific enolase. Serum contained IgG, which reacted with neuronal and glial cytoplasm and processes. IgG reactivity with systemic tissues and the patient's tumor was not different from that observed with control sera. Paraneoplastic optic neuropathy should be considered in patients with unexplained visual loss and malignancy, and our observations suggest a possible immunologic basis for this condition.

High-dose methotrexate in small cell lung cancer. Lack of efficacy in preventing CNS relapse.

Few studies have incorporated high-dose methotrexate (MTX) with leucovorin rescue in the treatment of small cell lung cancer (SCLC). Potentially therapeutic levels of MTX can be achieved in the central nervous system (CNS) by systemic administration of high doses of this drug. Utilizing a combination chemotherapy program of Adriamycin, vincristine, cyclophosphamide, and methotrexate, 31 patients were sequentially assigned to receive either low-dose MTX (40 mg/m2), or high-dose MTX (500 mg/m2) with leucovorin rescue. Radiation therapy to the primary site was also administered. At these dosage levels there were no statistically significant differences in response rate or survival between the two groups. High-dose MTX did not prevent the appearance of CNS disease; there being 2/15 and 3/15 CNS relapses in the HD MTX and LD MTX treated groups, respectively. The occurrence of CNS disease did not significantly affect overall survival as compared to patients not similarly affected.