High levels of serum sclerostin and DKK1 in a case of Klippel-Trénaunay syndrome.

Klippel-Trénaunay syndrome (KTS) is described as a complex syndrome characterized by various combinations of capillary, venous, and lymphatic malformations associated with bone and soft tissue hypertrophy. We report a case of a 67-year-old postmenopausal Caucasian women with KTS that shows elevated levels of sclerostin and Dickkopf-related protein 1 (DKK1). Dual-energy X-ray absorptiometry (DXA) BMD T-scores at lumbar spine and femur were normal. Serum calcium and phosphorus levels were consistently normal, 25-hydroxyvitamin D (25OHD) < 30 ng/mL, and normal parathyroid hormone (PTH). Turnover markers (serum osteocalcin [OCN], and carboxy-terminal cross-linking telopeptide of type 1 collagen [CTx]) were in the reference limits. It is interesting to note that the serum levels of sclerostin and DKK-1 were significantly higher in our patient with KTS than in a healthy volunteer (control), without impact on bone mineral density and bone formation markers. In fact, in our patient, the BMD at lumbar spine and femur was normal, and osteocalcin was not suppressed. Based on what is known, we would have expected to find low levels of the inhibitors of the Wnt system, perhaps we can explain the data as a response to the compensation for ß-catenin hyper-transformation.

Cyberknife® system: a new therapeutic strategy for sinonasal solitary extramedullary plasmacytomae.

Sino-nasal solitary extramedullary plasmacytoma (EMP) is a rare neoplasm with unpredictable progression to multiple myeloma. To improve the precision of irradiation delivery, preserving the healthy surrounding tissue and critical structures we used a CyberKnife® for the treatment of sinonasal solitary extramedullary plasmacytoma. We present the first case of sinonasal-EMP treated with CyberKnife®-stereotactic radiotherapy (SRT) with a complete remission without adverse events. Based on the post-therapeutic results and healthy tissue preservation, we believe that CyberKnife®-SRT represents a good therapeutic option for the treatment of sinonasal-EMP.

Painful bone metastasis in elderly treated with radiation therapy: Single- or multiple-fraction regimen? A multicentre retrospective observational analysis.

BACKGROUND: Bone metastases are a frequent complication of advanced oncologic disease. Pain associated to bone metastasis is a major cause of morbidity in cancer patients, especially in elderly. AIMS: The aim of this multicentric retrospective observational study is to evaluate the efficacy of different schedules of radiation therapy in elderly patients in terms of pain relief. METHODS: 206 patients over the age of 60 were enrolled in 1 year time for a multicentre retrospective observational study. Patients were treated with palliative purposes for painful bone metastases. RESULTS: Pain intensity difference (PID) was found in 72% of patients. Reported PID was statistically significant for p < 0.01. Pain intensity measured by a point numeric rating scale was statistically significant reduced for p < 0.05 by one-fraction regimen compared to other two regimens. DISCUSSION: In recent years, numerous studies have evaluated the most appropriate regimen of fractionation in individual cases, despite this, a consensus about the best schedule is still debated. CONCLUSIONS: On our analysis, single-fractionation scheme (8 Gy) confirmed to be statistical significant effective in providing pain reduction due to bone metastases. Radiation therapy provides significant pain relief of symptomatic bone metastases, but appropriate radiotherapy scheduled is needed in order to get significant response to treatment. Multidisciplinary approach is warranted to value the balance between the therapeutic objectives and the patient quality of life.

COVID-19 and radiotherapy: potential new strategies for patients management with hypofractionation and telemedicine.

COVID-19 disease is one of the biggest public health challenges in Italy and global healthcare facilities, including radiotherapy departments, faced an unprecedented emergency. Cancer patients are at higher risk of COVID-19 infection because of their immunosuppressive state caused by both tumor itself and anticancer therapy adopted. In this setting, the radiation therapy clinical decision-making process has been partly reconsidered; thus, to reduce treatment duration and minimize infection risk during a pandemic, hypofractionated regimens have been revised. Moreover, telemedicine shows its helpfulness in the radiotherapy field, and patients get the supportive care they need minimizing their access to hospitals. This review aims to point out the importance of hypofractionated RT and telemedicine in cancer patient management in the COVID-19 era.

Management of recurrent nasopharyngeal carcinoma: current perspectives.

Nasopharyngeal carcinoma is a rare disease in Western countries. Nevertheless, its incidence in China, Singapore, and other Eastern countries reaches 20 cases per 100,000 people. Being an extremely chemo- and radiosensitive disease, upfront treatment often consists in the association of intensity-modulated radiation therapy and concurrent cisplatin. Unfortunately, about 20% of the patients suffer from a radioresistant disease which recurs after upfront therapy. For these patients, mainly available therapeutic options consist in systemic therapy, in particular poly-chemotherapy. In those showing a single locoregional recurrence, chemotherapy is not considered to be the preferred approach and other different strategies may be employed. Re-irradiation and surgery are strategies that are always used more often, albeit related to high risk of morbidity. Immunotherapy and targeted therapy, such as heavy ions-based re-irradiations, are experimental but very intriguing options.

Translational Research: A Future Strategy for Managing Squamous Cell Carcinoma of the Head and Neck?

BACKGROUND: Squamous Cell Carcinoma of the Head and Neck (SCCHN) are neoplasms arising from the epithelium of the first aero-digestive tract. They are very heterogeneous both clinically and biologically. Classic and well acknowledged risk factors are alcohol and tobacco consumption and other forms of smokeless tobacco assumption, although lately the incidence of Human Papilloma Virus (HPV)-related SCCHN is rapidly increasing. HPV-related tumors are very different from their alcohol and tobacco-associated counterpart, as they show strong chemo and radio sensitivity and thus can often be treated with conservative treatment strategies. Moreover, peculiar biologic features characterize HPV-related tumors, such as wild type TP53, low expression of Epidermal Growth Factor Receptor (EGFR), wild type CCND1 and high expression of P16. In contrast, alcohol and tobacco related SCCHN show opposite features, together with higher number of chromosomal and genetic abnormalities, conferring them chemo and radio resistance. METHODS: We have performed a narrative review of the PubMed database with the aim to study the mutational landscape of SCCHN. RESULTS: Several lines of evidence support the existence of at least two genetically different types of SCCHN, one virus-related and the other alcohol and/or tobacco-related, characterized by both clinical and biological opposite features. Virus related SCCHN are very chemo and radiosensitive, so suitable for organ preserving strategy, which in the near future may be induction chemotherapy followed by association of chemotherapy and underpowered radiotherapy. Alcohol and tobacco related SCCHN are themselves strongly heterogeneous and can be divided in different entities on the basis of the "Driver" genetic aberration, responsible for carcinogenesis. The most frequently mutated genes in alcohol and tobacco-related SCCHN are TP53, NOTCH1, CCND1, CDKN2A, EGFR and PI3KCA. CONCLUSIONS: Virus-related SCCHN can be managed with chemo-radiotherapy. Alcohol and tobacco-related tumors should be further characterized on the basis of their "Driver Mutations" in order to select effective targeted therapies.

Rectal/urinary toxicity after hypofractionated vs. conventional radiotherapy in high risk prostate cancer: systematic review and meta analysis.

OBJECTIVE: The aim of our report was to review the literature concerning the toxicity of radiation therapy in patients treated for high-risk prostate cancer, and to evaluate the differences in toxicity between conventional fractionation and hypofractionated treatments, in view of different techniques used in high-risk prostate cancer patients. MATERIALS AND METHODS: PubMed database has been explored for studies concerning acute and late urinary/gastrointestinal toxicity in high-risk prostate cancer patients treated with radiotherapy. Prospective studies, concerning potential relationship between acute/late genitourinary (GU)/gastrointestinal (GI) toxicity and prostate radiotherapy in patients with high-risk prostate cancer, were included in the final analysis. Data collected from single arm, phase II non-randomized and randomized studies have been evaluated to perform odds ratio for toxicity risk. Furthermore, meta-analysis randomized prospective trials were considered suitable because they had recruited high-risk prostate cancer patients who didn't undergo surgery, with available data on ≥ G2 toxicity frequency. RESULTS: The initial search provided 606 results, but only 35 manuscripts met all eligibility requirements and were included in this report. In order to perform odds ratio we observed a decrease in late gastrointestinal toxicity for patients treated with hypofractionated schemes compared to CV treated ones. Among patients who underwent conventional treatment, SIB seemed to decrease acute genitourinary side effects; SIB-Hypo treated patients suffered less toxicity than patients treated with hypofractionated- sequential boost schemes. Hypo-SIB schemes would seem less toxic in terms of acute gastrointestinal and late genitourinary side effects than CV-SIB. Therefore, our focus shifted to 6 clinical trials evaluating genitourinary and gastrointestinal toxicity in patients who had been randomized to receive conventional fractionation or hypofractionated treatment, in both cases with IMRT technology. Our meta-analysis of these randomized trials involving patients with high-risk prostate cancer showed a statistically significant increase in late genitourinary toxicity for hypo-treated patients; no difference was observed in acute genitourinary/gastrointestinal toxicity, and in late gastrointestinal toxicity. CONCLUSIONS: Our analysis doesn't want to establish a definitive truth; very few trials assessed only high risk-class patients. Our purpose is to stimulate further randomized prospective trials focusing both on the effectiveness and toxicity profile (toxicity/effectiveness ratio), taking into account the use of different technologies and doses.

Somatostatin receptor subtype specificity and in vivo binding of a novel tumor tracer, 99mTc-P829.

Recent data suggest that somatostatin receptors (SSTRs) are expressed on various tumor cells. High-level expression of SSTR on the tumor cell surface provides the basis for the successful clinical use of radiolabeled ligands for the in vivo localization of tumor sites. We have characterized the in vitro binding properties of the novel SSTR ligand 99mTc-P829 using primary human tumors (carcinoids, breast cancers, intestinal adenocarcinomas, pheochromocytomas, small cell and non-small cell lung cancer, and melanomas; n = 28), various tumor cell lines, and COS7 cells transfected with the human SSTR (hSSTR) subtypes 1, 2, 3, 4, and 5. 99mTc-P829 bound to primary tumor cells and tumor cell lines with high affinity and high capacity. The dissociation constants (Kd) ranged between 1 and 20 nM. 99mTc-P829 also bound with high affinity to the transfected hSSTR2 (Kd, 2.5 nM), hSSTR5 (Kd, 2 nM), and hSSTR3 (Kd, 1.5 nM). Binding of 99mTc-P829 to hSSTR3 was found to be displaceable by unlabeled P829/([ReO]-P829), SST-14, and vasoactive intestinal peptide (VIP; IC50, 2 nM) and, less effectively, by Tyr3-octreotide (IC50, 20 nM). In contrast, the binding of 99mTc-P829 to hSSTR2 and hSSTR5 could be displaced by P829/([ReO]-P829) and Tyr3-octreotide but not by VIP. 99mTc-P829 scintigraphy revealed in vivo binding to primary or metastatic tumor sites in seven of eight patients with breast cancer and six of six patients with melanoma. In summary, our data show that 99mTc-P829 binds with high affinity to many different types of primary and cloned tumor cells. Furthermore, our data identify hSSTR2, the VIP acceptor hSSTR3, and hSSTR5 as the respective target receptors. Because these receptors are frequently expressed at high levels on primary tumor cells, 99mTc-P829 appears to be a promising novel peptide tracer for tumor imaging.

Detection of a numeric value predictive of increased dose to left anterior descending coronary artery (LAD) in radiotherapy of breast cancer.

PURPOSE: We have evaluated thoracic conformation of patients in order to derive a numeric value predictive of an increased dose to left anterior descending coronary artery (LAD), critical structure for the development of late radio induced cardiac morbidity. METHODS: We have evaluated 91 patients (36-88 years) affected by breast cancer stage I-II (Tis-T1-2 N0-1), undergoing adjuvant radiotherapy with conventional fractionation. For each patient on CT images was measured the distance between the back face of the sternum (manubrium) and the anterior face of body of the corresponding vertebra (a), and the distance measured on the line at 45° between the vertebral body of the same vertebra and the back face of the rib corresponding (b). The a/b ratio showed values between 0.626 and 1.123. We used the median value (0.821) as cut-off to divide the patients in two groups. We calculated in both groups: Volume (Vol) heart, Vol LAD with an expansion of 0.6 mm; Dmean LAD (Gy); Dmax LAD (Gy); V10-V20-V30 (%) LAD and we correlated these values with parametric and non-parametric tests. RESULTS: The Pearson test has showed a statistically significant correlation between Vol breast and V10, V20, V30 with borderline significance (p = 0.006; p = 0.02; p = 0.05). The data were confirmed by testing non-parametric Kendall (tau = 0.004; tau = 0.015; tau = 0.016) and Spearman (rho = 0.003; rho = 0.016; rho = 0.015). We conducted categorizing into quartiles of breast volume and evaluated the correlation with a/b. We have found a significative correlation (p = 0.01) between small Vol breast (≤660.23 cc) and a/b < 0.0821 and greater Vol breast (>660.23 cc) with a/b > 0.0821. From the evaluation of the distribution of V10 in the two groups taking account of the Dmean ≤5 or >5 significance was found with a/b; Chi square 0.009 (0.01). Values ≤5 were observed in women with a/b < 0.0821. Values >5 in women with a/b > 0.0821. CONCLUSIONS: The geometric conformity of chest thorax considering a/b and the value of 0.0821 can reveals an important parameter in the selection of patients suitable for radiation therapy on left breast in order to evaluate the risk of late cardiac events. This consideration during treatment planning can change the technique or the set-up allowing the development of a customized plan.

Orbital scintigraphy with [111In-diethylenetriamine pentaacetic acid-D-phe1]-octreotide predicts the clinical response to corticosteroid therapy in patients with Graves' ophthalmopathy.

Corticosteroid treatment is successfully used in Graves' ophthalmopathy, and its effect varies according to the phase of the disease. The infiltration of the orbit by activated lymphocytes may explain the effectiveness of corticosteroid therapy. Scintigraphy with [111In-DTPA-D-Phe1]-octreotide was recently used to reveal the presence of activated lymphocytes in foci of autoimmune diseases, because elevated amounts of somatostatin receptors are expressed in the surface of these cells. The aim of the current study was to evaluate whether the degree of orbital [111In-DTPA-D-Phe1]-octreotide uptake is able to predict the response to corticosteroid therapy in patients with Graves' ophthalmopathy. Ten patients with Graves' ophthalmopathy entered the study. In all patients scintigraphy was performed, and subsequently, corticosteroid therapy (methylprednisolone, 1 g i.v. for 2 consecutive days a week for 6 weeks) was given. Clinical activity of Graves' ophthalmopathy was evaluated before and after treatment by calculating the ophthalmopathy index (OI). Planar and single photon emission computed tomography (SPECT) images of the head were obtained 24 h after the i.v. injection of 120-190 MBq of [111In-DTPA-D-Phe1]-octreotide. Radioligand uptake within each orbit (O) and brain (B) was measured using the region of interests (ROI) method and the O-to-B ratio was determined. According to the O-to-B ratio, the images were classified using the following three points score: 0 = O-to-B ratio < or =1; 1 = O-to-B ratio between 1 and 2.5; 2 = O-to-B ratio > or =2.5. The value of OI, measured before and after corticosteroid treatment, was correlated to the scintigraphic score. A significant change of OI was observed between posttreatment and pretreatment evaluation both in orbits with score 2 (OI: 15.4 +/- 1.5 vs. 9.6 +/- 0.5, P < 0.005) and in those with score 1 or 0 (OI: 12.9 +/- 1.5 vs. 11.5 +/- 1.4, P < 0.05) at the scintigraphy. However, when the OI was calculated excluding the changes in the soft tissue, which generally occur in all patients independently from the phase of the disease, a significant change of OI was observed only in the orbits with score 2 (OI: 12.9 +/- 1.3 vs. 8.3 +/- 0.5, P < 0.01) but not in those with score 0 or 1 (OI: 11.2 +/- 1.3 vs. 10.4 +/- 1.3). In particular, 6 weeks after corticosteroid treatment, the patients with orbital score 2 at the scintigraphy had a significant improvement of soft tissue changes, proptosis, lagophthalmos, extraocular muscle movements impairment, and diplopia, whereas patients with score 0 or 1 had only a significant improvement of the soft tissue inflammation. In conclusion, the current preliminary data suggested that [111In-DTPA-D-Phe1]-octreotide scintigraphy is able to predict the clinical response to corticosteroid treatment in patients with Graves' ophthalmopathy, and may be considered an useful approach to select the patients for the proper treatment.

Accelerated split-course (type B) thoracic radiation therapy plus vinorelbine/carboplatin combination chemotherapy in stage III inoperable non-small cell lung cancer.

43 patients with stage III NSCLC (non-small cell lung cancer) entered a phase II study aimed at evaluating the toxicity and the activity of a combined modality programme including an accelerated split-course schedule (type B) of thoracic radiation therapy and a combination chemotherapy with vinorelbine and carboplatin. An objective response was achieved in 18/42 evaluable patients (5 complete and 13 partial responses), for an overall response rate of 43% (95% confidence interval, 28-58%). Four complete responses had a duration which exceeded 16 months. Treatment was well tolerated; grade III myelotoxicity occurred in only 14% of patients and treatment was delayed in only 2 cases because of grade 3 oesophagitis. Both tolerability and efficacy data suggest that this regimen holds promise for the treatment of patients with stage III NSCLC.

Technetium-99m-methylene diphosphonate scintimammography to image primary breast cancer.

UNLABELLED: Technetium-99m-methylene diphosphonate (MDP) uptake within breast lesions was investigated during routine presurgical bone scintigraphy in a cohort of women at high risk for cancer who were candidates for surgery or excisional biopsy. The aim was twofold: (a) to demonstrate positive 99mTc-MDP uptake in primary breast cancer and (b) to differentiate malignant from benign lesions. METHODS: Anterior and oblique lateral views of the breasts were acquired 0-4 min, 10-20 min and 2 hr after intravenous injection of 740 MBq of 99mTc-MDP in 200 women with elevated suspicion or proven diagnosis of breast cancer (Group 1) and in 80 women with other solid tumor types (Group 2). RESULTS: Physical examination and mammography revealed breast abnormalities in all Group 1 subjects. The mammographic findings were definitely positive for carcinoma in 120 patients, highly suspicious in 27 and indeterminate in 53. Breast cancer was later histologically diagnosed in 172 women (86%) and benign disease found in 28 women (14%). Of these patients, 158 (92%) showed focal uptake of 99mTc-MDP in the images collected 10-20 min after injection. This was found to be the best timing for imaging, with tumor-to-background ratios as high as 4.3 (mean +/- s.d. = 3.8 +/- 0.4). Two hr after injection, only 61 of the 158 (38%) malignant lesions were clearly detectable. CONCLUSION: Technetium-99m-MDP is concentrated by primary breast carcinoma 10-20 min after injection, enabling successful external gamma imaging. Scintimammography with 99mTc-MDP is an accurate test that differentiates malignant from benign breast lesions, particularly in patients with indeterminate mammograms.

In vivo detection of malignant thymic masses by indium-111-DTPA-D-Phe1-octreotide scintigraphy.

UNLABELLED: Many tumors with neuroendocrine characteristics express high amounts of somatostatin receptors that enable in vivo imaging with [(111)In-DTPA-D-Phe1]-octreotide. In this study, we have analyzed the feasibility in detecting and characterizing thymic masses by somatostatin receptor scintigraphy (SRS). METHODS: Eighteen patients (13 women, 5 men, ages 18-78 yr; mean +/- s.d. = 42.1 +/- 17.6 yr) were enrolled in this study. Eleven patients were studied during diagnosis and seven during routine follow-up. In seven patients, myasthenia gravis was the presenting symptom. SRS was performed within 4 wk after CT and/or MRI. Planar and tomographic images were acquired within 24 hr after the injection of approximately 111 MBq of [(111)In-DTPA-D-Phe1]-octreotide. The scintigraphic results were categorized according to the histologic findings. RESULTS: Histology diagnosed 10 mixed epithelial/lymphoid thymomas (8 with prevalent epithelial component), 2 thymic carcinomas, 1 thymic carcinoid, 1 lymphangioma and 4 thymic hyperplasias. Two thymoma were Stage I, 3 were Stage II, 2 were Stage III and 5 were Stage IV, as was the thymic carcinoid. Indium-111-DTPA-D-Phe1-octreotide concentrated in primary and/or metastatic sites of thymic tumors, thereby enabling successful external gamma imaging of sites greater than 1.5 cm in size. Tumor-to-lung (T/L) ratios were as high as 7.6-fold (range 1.7-7.6). Untreated thymomas showed higher T/L (4.34 +/- 1.57) than treated ones (2.68 +/- 1.18). No uptake was detectable in the four patients with benign thymic hyperplasia and the patient with the lymphangioma. CONCLUSION: Indium-111-DTPA-D-Phe1-octreotide is avidly concentrated within thymic tumors, but it is not concentrated by thymic hyperplasia, which allows differential diagnosis. Thus, in patients with myasthenia gravis, SRS may have a role in characterizing thymic masses, thereby overcoming the limits of cross-sectional imaging modalities.

Detecting deep venous thrombosis with technetium-99m-labeled synthetic peptide P280.

UNLABELLED: Scintigraphy, using small, thrombus-avid, synthetic peptides labeled with gamma-emitting nuclides is an innovative approach to the noninvasive detection of acute deep venous thrombosis (DVT). The goal of this study was to evaluate clinically 99mTc-P280 for imaging DVT. The peptide P280 is a 26 amino acid dimer that binds with high affinity to the GPIIb/IIIa receptor expressed on activated platelets and can be labeled with 99mTc. METHODS: Scintigraphy with 99mTc-P280 (10-22 mCi) was performed in nine patients with clinical suspicion and diagnostic evidence of DVT. Planar and tomographic images of the legs, abdomen/pelvis, chest and head were obtained immediately, 1, 2, 4 and 24 hr after injection. RESULTS: No adverse effects were noted after 99mTc-P280 administration in any patient. Positive visualization of thrombi occurred in eight of nine cases with confirmed DVT within 1 hr of tracer injection. The majority of the patients had recent onset of DVT symptoms (less than 3 wk), while the only negative case was diagnosed 42 days earlier and was likely related to an accident 7 mo earlier. Thrombi-to-background ratios were essentially constant over the study. Technetium-99m-P280 accumulation was also discernible in two patients with pulmonary embolism, while in a third patient the radiotracer concentrated in a cerebellar hemangioblastoma. CONCLUSION: These human studies indicate that 99mTc-P280 is a potentially safe and sensitive procedure for diagnosing DVT and pulmonary embolism. It also may have substantial utility in monitoring active venous thrombosis.

Primary Ewing's sarcoma of the maxilla, a rare and curable localization: report of two new cases, successfully treated by radiotherapy and systemic chemotherapy.

Primary maxillary localization of Ewing's sarcoma is unusual. Involvement of facial bones is characterized by clinical and radiological features distinct from those commonly observed in other sites. Because of the above peculiarities a delay in diagnosis and thus in starting treatment is very probable in such cases. We report here two new cases of Ewing's sarcoma localized to facial bones, successfully treated by local high dosage radiotherapy and systemic chemotherapy. Our experience suggests that, especially for particular sites not suitable to radical surgery, radiation therapy can represent an effective tool to achieve local control of the tumor.

Radiation late effects in children treated for orbital rhabdomyosarcoma.

BACKGROUND AND PURPOSE: The experience resulting from large cooperative studies shows that correct radiation therapy at doses adequate to the tumor bulk are crucial for local control of rhabdomyosarcoma. The aim of the present study was to document the correlation between modalities and doses of radiotherapy and radiation side effects. PATIENTS AND METHODS: Between 1980 and 1997, 19 patients affected by primary orbital rhabdomyosarcoma have been followed at the University Federico II of Naples. All but three patients, who received 45, 54 and 55 Gy respectively, have been treated by immediate radiation at the dose of 60 Gy, delivered in 2 Gy fractions, five times per week, by cobalt 60 megavoltage equipment. Combined chemotherapy using vincristine and vincristine plus dactinomycin on alternate weeks was also administered as part of induction therapy. RESULTS: An overall survival rate of 94.7% was registered. In our patients the majority of radiation late effects were paid by orbit and ocular adnexa. Side effects to lens and ocular structures were fewer and of low grade. CONCLUSIONS: Radiation therapy is still essential for local control of orbital rhabdomyosarcoma, however radiation side effects have to be carefully considered together with the therapeutic goal to be obtained.

Hyperfractionated split-course thoracic radiation-therapy plus chemotherapy in locally advanced nonsmall cell lung-cancer.

Hyperfractionated split course radiotherapy combined with carboplatin, etoposide and mitomycin C was administered to 76 patients with stage III non-small cell lung cancer. Grade 4 leukopenia occurred in 5 patients; 4 toxic deaths were observed. The overall response rate was 45%, including a 9% rate of complete responses, which lasted > 12 months in four cases. The median survival was 13 months, 2-year progression-free survival 17%, actuarial 2-year survival rate 22%. Age > 65, performance status > 1, no response to prior treatment were predictors of poor outcome. Our treatment plan, particularly because of the long lasting complete responses, warrants further investigation.

Phase I-II study of gemcitabine and paclitaxel in pretreated patients with stage IIIB-IV non-small cell lung cancer.

Gemcitabine and paclitaxel are among the most active new agents in non-small cell lung cancer (NSCLC) and are worth considering for second-line chemotherapy. In this phase I-II study, we combined gemcitabine and paclitaxel for second-line treatment of advanced NSCLC. Gemcitabine doses were kept fixed at 1000 mg/m2 on day 1 and 8, and paclitaxel doses were escalated from 90 mg/m2 on day 1 of the 21-day cycle. Thirty-seven patients were treated at six different dose levels. Grade 4 neutropenia was dose-limiting toxicity (DLT), since it occurred in two out of six patients treated at paclitaxel 240 mg/m2; the paclitaxel dose level just below (210 mg/m2) was selected for phase Il evaluation. Non-hematologic toxicity was mild. One complete response (CR) (3%) and 13 partial responses (PR) (36%) were observed in 36 evaluable patients for an overall response rate of 39% (95% C.I., 23-57%). Median duration of response was 35 weeks (range, 8-102). All of the observed objective responses occurred in the 19 patients who had previously responded to the first-line therapy. Median survival was 40 weeks (range, 8-108 weeks). The combination of gemcitabine and paclitaxel is a feasible, well-tolerated, and active scheme for second-line treatment of advanced NSCLC; further evaluation, at least in selected patients, such as those previously responding to first-line chemotherapy, is definitely warranted.

Phase I study of vinorelbine and paclitaxel in small-cell lung cancer.

BACKGROUND: Vinorelbine and paclitaxel interfere with mitotic spindle function through different mechanisms of action. Both of the drugs show antitumor activity in small-cell lung cancer when used as single agents; furthermore, in vitro and in vivo studies have shown a synergistic activity between the two drugs. PATIENTS AND METHODS: Patients with small-cell lung cancer no longer amenable to conventional treatment were entered into a phase I study in which vinorelbine was given at a fixed dose of 30 mg/m2 by 15-min intravenous infusion, whereas paclitaxel was given by 3-h infusion starting 1 h after vinorelbine at an initial dose of 90 mg/m2, which was subsequently escalated by 30-mg/m2 steps. Cycles were repeated every 21 days. RESULTS: Grade 3 neutropenia was observed only in three patients treated at the fifty dose level. Thrombocytopenia never reached grade 3. Neurotoxicity was considered dose-limiting, since grade 3 peripheral neuropathy occurred in three of five patients treated at the fifth dose level (paclitaxel 210 mg/m2). Other side effects were generally mild. The overall response rate in 22 evaluable patients was 32% (95% CI 13-51%); in particular, 1 complete response (4.5%) and 6 partial responses (27.3%) were observed. The maximally tolerated doses recommended for phase II studies are 180 mg/m2 for paclitaxel and 30 mg/m2 for vinorelbine. The observed myelosuppression was less severe than anticipated on the basis of the effects of each drug alone. CONCLUSIONS: The promising activity of this drug combination warrants a phase II study in untreated patients with extensive-stage small-cell lung cancer.

The role of radiolabeled somatostatin analogs in adrenal imaging.

We investigated the role of radiolabeled somatostatin analogs (SAs) in adrenal imaging. We evaluated 15 patients (6 men and 9 women, mean age 47 +/- 17 years) with imaging-detected adrenal tumors. Patient population was divided into two groups on the basis of the nature of adrenal lesions. Group 1 consisted of patients with benign adrenal lesions (n = 10). Group 2 consisted of patients with malignant adrenal lesions (n = 5). Pathology examinations were obtained in 13 cases: 7 pheochromocytomas, 2 adenomas, 2 cysts, 1 carcinoma, and 1 fibro-histiocytoma. One patient had a proven diagnosis of non-small-cell lung cancer associated with the presence of a right adrenal mass. The last patient had a clinical diagnosis of Werner syndrome associated with the presence of a large left adrenal mass. All patients underwent scientigraphic studies using radiolabeled SAs, of which indium-111 (In-111) pentetreotide was used in 11 cases and technetium-99m (Tc-99m)-labeled peptides (P-587 or P-829) were used in the remaining four cases. No significant labeled SAs uptake was observed in the majority (8 of 10, 80%) of the benign adrenal lesions (Group 1); however, increased uptake was found in two benign pheochromocytomas. Conversely, significant labeled SAs uptake was observed in the majority (4 of 5, 80%) of the malignant adrenal lesions (Group 2); however, the last lesion (carcinoma) did not show abnormal uptake. Results of this study show that the majority of benign adrenal tumors do not concentrate radiolabeled SAs; conversely, the majority of malignant adrenal lesions show significant SAs uptake, suggesting the presence of somatostatin receptors. This finding may allow the use of somatostatin as a treatment agent in malignant adrenal tumors. Thus, the main role of labeled SAs in adrenal imaging consists of lesion characterization rather than tumor detection and localization.