Tumori Journal

Basal cell carcinoma (BCC) is the most common skin cancer. Treatment options for metastatic or locally advanced BCC inappropriate for surgery or radiotherapy were poor until vismodegib was approved for use in this setting. This drug can be safely used in patients with mild to moderate renal impairment, but limited data are available for its use in case of severe kidney failure. We present the case of a patient with severe renal failure on hemodialysis treated with vismodegib.

An 83-year-old patient with relapsing BCC of both auricles and severe renal failure on hemodialysis was treated with vismodegib for 7 months. The treatment proved to be effective with a striking reduction of the tumor masses. The patient was on therapy with vismodegib for 7 months and no severe adverse event was observed.

Vismodegib could be used in patients with severe renal impairment, but these patients must be attentively followed and strict cooperation among healthcare professionals, such as nephrologists, dermatologists, and medical oncologists, is required.

Signet-ring cell (SRC) carcinoma is a common subtype of gastric adenocarcinoma associated with poor prognosis. Metastatic involvement of the parotid gland has been reported in gastric cancer patients, but never bilaterally nor in association with the SRC histotype. Here, we report the first case and a brief review of the literature.

A 47-year-old woman was referred to our center for a signet-ring gastric carcinoma with synchronous hepatic and peritoneal metastases. After 3 lines of chemotherapy, the patient reported a progressive bilateral enlargement in the periauricolar area. An ultrasound of the salivary glands and a fine needle biopsy were diagnostic for parotid metastases of gastric origin. In the literature, only 3 cases of parotid gland metastases arising from gastric cancer are described – none with a feature of SRC carcinoma.

To the best of our knowledge, this is the first report of gastric SRC carcinoma with bilateral parotid metastases. This case highlights the importance of considering a parotid enlargement as a possible sign of disease progression in a patient with gastric cancer. Fine-needle biopsy and immunocytochemistry are essential in establishing the origin of the secondary lesion.

In patients with cutaneous graft versus host disease (GvHD) that is resistant to traditional steroid therapy, imatinib is a first-generation tyrosine kinase inhibitor that seems to be a viable option. However, its antifibrotic activity can be associated with serosal inflammation and fluid retention.

We report a case of an adult patient who, after allogenic hematopoietic stem cell transplantation, developed a GvHD treated with imatinib at low dosage, followed by multiorgan failure. Clinical examination and cardiac ultrasound were unable to clearly recognize the low cardiac output state; laboratory analysis, filling pressure, and computed tomography examination clarified the correct diagnosis.

Low cardiac output state, secondary to pericardial effusion, is a diagnostic challenge. However, the association of four elements can help in its early recognition: increase in lactate levels and central venous pressure, associated with a low central venous saturation and a low brain natriuretic peptide level.

Pericardial effusion with cardiac tamponade is a difficult diagnosis even with ultrasound. Lactate levels, central venous pressure plus venous saturation, and brain natriuretic peptide could help in early detection.

To describe a case of giant intercostal nerve schwannoma successfully resected in a patient with neurofibromatosis type 2.

A 44-year-old woman, with a history of neurofibromatosis type 2, presented with chest discomfort and mild dyspnea. She had undergone a recent resection of a large frontal parasagittal benign meningioma. Radiologic examinations showed a large lesion (9×12×9 cm) of the left hemithorax causing a complete atelectasis of left upper lobe. Bronchoscopy did not show any endobronchial alterations, apart from an ab estriseco compression of the left upper bronchial tree. A transthoracic needle biopsy was then performed and microscopic examination revealed a mesenchymal tumor composed of spindle-like cells.

A video-assisted thoracoscopic surgery procedure was proposed. The tumor mass appeared to be tenaciously adherent to the parietal pleura in its anterolateral aspect, confirming the radiologic appearance. No invasion of the lung parenchyma or parietal pleural metastases were visible. Therefore, a left posterolateral thoracotomy at the fifth intercostal space was performed and a macroscopic complete resection was carried out. The recovery was uneventful and the patient was discharged on postoperative day 5. The histologic examination revealed a moderate cellular proliferation of spindle-shaped and oval to polygonal cells with frequent Verocay bodies; mitotic figures were rare. The tumor cells were strongly S-100 positive. The microscopic features were consistent with benign intercostal schwannoma. Eight years later, the patient is disease-free and asymptomatic.

An unusual case of giant intercostal nerve schwannoma successfully resected in a patient with neurofibromatosis type 2 is described.

Hypereosinophilic syndrome (HES) is a rare condition characterized by eosinophilia and organ destruction secondary to eosinophilic infiltration. The coexistence of primary B-cell lymphoma and hypereosinophilic syndrome is extremely rare. We present a case of HES that preceded the diagnosis of diffuse large B-cell lymphoma.

A 70-year-old man presented with a 3-month history of diarrhea and 30-pound weight loss. Complete blood count showed a white blood cell count of 7452/µL with eosinophils of 42% (absolute eosinophil count 3130). Colonoscopy showed eosinophilic infiltrate in the lamina propria and muscularis mucosa. Bone marrow biopsy showed elevated myeloid: erythroid ratio (6:1), increased mature and immature eosinophilic infiltration (10% of nucleated cells). Molecular studies were negative for Fip1-like1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRA) translocation and PDGFRB and FGFR mutations, indicating nonclonal eosinophilia. Treatment was initiated with prednisone (1 mg/kg) and hydroxyurea 500 mg twice daily. He responded with complete resolution of symptoms. Five months later, the patient presented with right lower quadrant pain. Abdominal/pelvis computed tomography (CT) showed bulky right inguinal lymphadenopathy and biopsy revealed CD10+ diffuse large B-cell lymphoma (DLBCL). Further staging workup showed the stage to be IIB. He received 6 cycles of chemotherapy and involved field radiation therapy. He achieved complete remission.

Reviewing the literature indicates only one case of similar presentation with concomitant HES and DLBCL. Eosinophilia is routinely encountered in clinical practice and as such physicians must be aware of the rarer, more malevolent underlying associations of this condition so as to aid early diagnosis and prompt treatment.

Early breast cancer follow-up guidelines for patients who underwent surgery suggest a regular and accurate clinical examination of the breast area, for an early identification of cutaneous or subcutaneous breast cancer relapse. Nonetheless, breast skin lesions arising in patients treated with mastectomy for breast cancer can be caused by several diseases. A series of diagnostic hypotheses should be considered, not only focusing on cutaneous metastasis, but also on dermatologic and systemic diseases.

In February 2015, a 37-year-old patient underwent a right subcutaneous mastectomy for stage IIA breast cancer. Five months after beginning adjuvant chemotherapy, she noted hyperpigmentation and thickening of the skin on the right breast. Differential diagnosis included local relapse, skin infection, lymphoma, or primary cutaneous disease, and a skin biopsy was performed. The histopathologic specimen showed full-thickness sclerosis, with features of localized morphea. Therapy with clobetasol was prescribed, with progressive resolution of the thickness. The collaboration between many professionals in a multidisciplinary team (oncologist, dermatologist, plastic surgeon, and pathologist) was crucial to achieving the diagnosis.

In the literature, some articles describe correlation between connective tissue diseases and silicone breast implants, but the pathogenetic mechanisms are unknown. We report a rare case of breast morphea after positioning a silicone implant in a patient who had undergone mastectomy. This clinical report represents an interesting model of multidisciplinary management of a patient with breast cancer who developed an uncommon dermatologic disease. Further studies are needed to clarify the association between silicone implants and breast morphea.

Treatment paradigms for EGFR-mutated non-small cell lung cancer (NSCLC) have successfully evolved since the introduction of osimertinib. The detection of EGFR T790M mutation in plasma or tumor samples obtained at disease progression to first-/second-generation EGFR inhibitors is mandatory for osimertinib prescription. Nevertheless, pharmacokinetics properties of osimertinib guarantee its usefulness in central nervous system (CNS) disease even in the case of T790M-negative or unknown status.

In this brief report, we share the clinical histories of two patients with CNS-preeminent progression under first-/second-generation EGFR inhibitors in which it was not possible to document the presence of T790M resistance mutation.

Patient outcomes diverged dramatically due to the differential availability of off-label osimertinib.

Waiting for the novel molecule to be approved and licensed in first-line treatment, our report of hope and frustration is intended to stress the opportunity of its administration in the case of CNS failure of first-line EGFR inhibition, even in the absence of T790M proof.

Peripheral neuroblastic tumors (PNTs) account for 8%–10% of all pediatric tumors. Adrenal glands and sympathetic ganglia are the commonest site of tumor growth. In the clinicopathologic spectrum of PNTs, neuroblastoma and ganglioneuroma are the most primitive and the most mature tumor form, while ganglioneuroblastoma represents an intermediate state of maturation. Surgical resection is the therapy of choice in localized disease, but can lead to serious complications when performed in the presence of certain imaging-defined risk factors.

We present a rare case of primary intrarenal ganglioneuroblastoma diagnosed in a teenager who underwent conservative surgery and, despite this, developed upper pole renal ischemia without loss of parenchymal function.

We underline the complex management of these extremely rare cases of neuroblastic tumors, which require a dedicated multidisciplinary team.

Diffuse gastric cancer is associated with poor prognosis. We report a patient with metastatic gastric linitis plastica harboring human epidermal growth factor receptor 2 (HER2) activating mutation and HER2 amplification.

The patient received 5-fluorouracil/folinic acid and oxaliplatin combined with trastuzumab/pertuzumab, resulting in disease control for 8 months. Second-line therapy with nivolumab and trastuzumab/pertuzumab was well-tolerated, with macroscopic peritoneal response. Following ovarian progression and surgical resection of ovarian metastases, immunohistochemistry of PD-L1 was negative; proteomics demonstrated normal expression of HER2 and absence of PD-L1, while genomics showed HER2 amplification, suggesting mechanisms of escape to dual HER2 blockade by downregulation of HER2 and to nivolumab by the absence of PD-L1. Based upon this and nonexpression of biomarkers of taxane resistance, therapy was changed to paclitaxel. Two and a half years after diagnosis, the patient is undergoing treatment, with excellent performance status.

Molecular analysis and personalized therapy can help optimize treatment in difficult-to-treat cancers.

Pseudochylothorax is a rare cause of pleural effusion. Sometimes confounded with chylothorax, firm diagnosis relies on analysis of the pleural liquid: exudative liquid (protein >30 g/L, lactate dehydrogenase >200 UI/L) with a high level of cholesterol (usually >200 mg/dL), low level of triglyceride (usually <110 mg/dL), cholesterol total/triglyceride ratio >1, absence of chylomicron, and in some cases the presence of cholesterol crystals. Pseudochylothorax is secondary to tuberculosis and rheumatoid arthritis in nearly 90% of cases. Its oncologic etiologies are mainly represented by malignant hematologic disorders.

We report the first case of pseudochylothorax whose cause was the pleural metastasis of an extrathoracic solid tumor in a 61-year-old man with a medical history of oropharynx carcinoma.

Computed tomography scan disclosed a left partitioned effusion of high abundance, responsible for a passive atelectasis of the left lower lobe and multiple bilateral pulmonary nodules. A drainage tube was inserted to allow the evacuation of serous liquid; biochemical examination revealed an exudative effusion with pseudochylothorax criteria. Because the daily chest drainage output remained greater than 1 L per day, videothoracoscopy pleural biopsies and talc pleurodesis were performed. Histopathologic examination of the pleural biopsies found a pleural localization of oropharynx carcinoma.

Because its occurrence is probably underestimated, when pseudochylothorax is diagnosed, oncologic causes should be considered.

Thoracic paravertebral block is a technique for perioperative analgesia in patients undergoing thoracic, chest wall, or breast surgery, or for pain management with rib fractures, which can be performed with or without ultrasound guidance. The ultrasound guidance technique can be used to identify the thoracic paravertebral space, guide needle placement, monitor the spread of local anesthetic (LA) solution, and reduce complications such as pleural puncture and pneumothorax. The possibility of assessing anesthetic spread in real time using ultrasound guidance during paravertebral block offers numerous advantages, including the immediate and accurate identification of the extent of nervous block, with a consequent reduction of LA dose. The real-time visualization of spread may be used to achieve good anesthetic cover by administering the block at a single level, thus reducing complications normally associated with the technique.

This case report describes the use of ultrasound-guided thoracic paravertebral block, at thoracic (T) 4 and 5 levels, in a patient undergoing breast surgery for perioperative analgesia. The authors were able to witness cranial diffusion of LA at T3-T4 in real time, and measure the increase in space between the costotransverse ligament and pleura, as an indication of anesthetic spread, at T2-T3 and T6-T7 levels.

This is the first known case in the literature of direct viewing of LA diffusion in a paravertebral space other than the one in which the block is administered and may open important scenarios for the improvement of anesthesia technique.

In case of pelvic recurrence of colorectal cancer, reirradiation of previously irradiated patients may increase the rate of salvage radical resection. Due to the high cumulative dose, one of the main concerns is radiation-induced lumbosacral plexopathy. This report describes multiple irradiations of a lesion adjacent to the lumbosacral plexus, using a highly selective technique, which allows optimal sparing of such a critical structure.

A 53-year-old woman treated in 2008 for a locally advanced rectal adenocarcinoma with preoperative pelvic irradiation and concomitant chemotherapy followed by surgery had disease recurrence in 2011 and underwent a second course of pelvic radiotherapy. In December 2015, magnetic resonance imaging showed a single local recurrence infiltrating the muscle next to the right lumbosacral plexus and close to the cauda equina. Repeat reirradiation was planned. The total dose deriving from the previous treatment plans was assessed by nonrigid image registration using the dedicated tool implemented in MIM 6.1.7 (MIMvista Corp., Cleveland, OH). The treatment was performed with Cyberknife (Accuray, Sunnyvale, CA) with a schedule of 20 Gy in 5 fractions (4 Gy per fraction). The dose was prescribed to 70% isodose and target coverage was 97%. Two months after the treatment, magnetic resonance imaging showed a decreased signal and stable disease with no change in tumor size.

This case report suggests that pelvic re-reirradiation might be a possibility in very carefully selected cases of rectal cancer, using high-precision radiation modalities.

Thoracic surgery can have serious side effects. Accurate preoperative evaluation to assess which patients with anatomically resectable disease are suitable candidates for surgery is mandatory.

A 58-year-old man, scheduled for left pneumonectomy for lung cancer, passed all the preoperative examinations suggested by guidelines and underwent the surgery. Three days after pneumonectomy, he experienced hemorrhagic shock and subsequent acute respiratory distress syndrome. Fifteen days after left pneumonectomy, he experienced exertional acute right heart failure (ARHF). We administered sildenafil and he improved, clinically and echocardiographically.

During the following 2 years of follow-up, he was asymptomatic at rest but under exercise test, he developed pulmonary hypertension with echocardiographic signs of right ventricular impairment.

In patients scheduled for major lung resections, preoperative stress echocardiography may give an adjunctive value to cardiopulmonary exercise test, quantifying the exercise-induced reduction in right ventricle ejection fraction and identifying asymptomatic patients at risk for postoperative ARHF.

Neutrophil-to-lymphocyte ratio (NLR) was shown to be prognostic in several solid malignancies. There are limited data about predictive/prognostic value of NLR during targeted therapy of patients with advanced gastrointestinal stromal tumors (GIST). The aim of this study was to asses a clinical value of this ratio in patients with advanced GIST.

Between 2001 and 2016, 385 patients with metastatic/unresectable GIST treated initially with imatinib were included in the analysis. In all patients, the NLR was assessed at the baseline, after 3 months of treatment, and upon disease progression (or last observation). The cutoff values for NLR were set at 2.7 and 5.4. Kaplan-Meier survival probability estimation with log-rank test and Cox proportional hazards model were used for analysis.

Median progression-free survival (PFS) on imatinib treatment was 44.8 months, 5-year rate 43%; median overall survival (OS) 87.2 months, 10-year rate 36.3%. NLR >2.7 at baseline was significantly associated with poorer OS and PFS: median OS was 89.3 months (95% confidence interval [CI] 80.2-115) for NLR ratio ≤2.7 vs 59.4 months (95% CI 48.6-82) for NLR >2.7 (p < .001); median PFS was 59.4 vs 32.7 (p < .001), respectively. In multivariate model adjusted for mitotic index and driver mutation in the tumor (KIT exon 11 mutation versus other), NLR ratio was proven to be statistically significant (hazard ratio 1.09; 95% CI 1.01-1.19; p = .030). Among patients with disease progression, NLR >2.7 assessed at the third month of treatment was linked with significantly shorter median time to progression (7.5 vs 19 months).

Our results demonstrate the usefulness of NLR as a prognostic and predictive marker as well as a marker for treatment monitoring in patients with advanced GIST treated with imatinib.

Metastases from colorectal cancer are poorly responsive to stereotactic ablative radiation therapy (SABR) due to intratumoral hypoxia. Intratumoral oxygenation is improved by administration of angiogenesis inhibitors. Thus, there could be a clinical synergistic effect of SABR with bevacizumab on metastases from colorectal cancer. The aim of this study was to evaluate the feasibility and efficacy of SABR after bevacizumab in lung oligometastases from colon cancer.

The data of patients with lung metastases from colon cancer who underwent SABR were retrospectively evaluated according to the following inclusion criteria: number of metastases ≤3; lung oligometastases from colon cancer in patients who underwent SABR; patients receiving previous chemotherapy alone or in combination with bevacizumab; Karnofsky performance status >80; life expectancy >6 months; at least 6 months’ follow-up after SABR; presence of KRAS mutation. The results were compared with those of a similar cohort of patients with irradiated lung lesions from colorectal cancer in whom bevacizumab was not previously administered.

A total of 40 lung metastases were analyzed. The complete response rate after SABR was higher in patients who had received bevacizumab than in those who had not (p = 0.04). Additionally, in the bevacizumab group, a higher rate of post-SABR complete response was observed in case of oligopersistent versus oligorecurrent metastases (p = 0.001).

In the setting of lung oligometastases from colon cancer the present study attested the higher efficacy of SABR after bevacizumab administration. Further studies in this field of research are strongly advocated.

To analyze the impact of adjuvant radiotherapy (RT) on ipsilateral breast recurrence (IBR) and overall survival (OS) in patients older than 69 years with early-stage breast cancer.

From January 2007 to June 2015, we analyzed retrospectively 137 women with estrogen receptor–positive T1–2 invasive breast cancer, with negative axillary lymph nodes, dividing them into 2 subgroups: 70 to 79 years and older than 79 years.

After a median follow-up of 43.2 months, the 3-year IBR-free survival in patients treated with surgery plus RT was 98.8% and 92.1% in patients treated with surgery alone, with a significant difference (p = .01). Radiotherapy did not impact overall survival (p = .10). A higher percentage of patients aged between 70 and 79 years received RT after conservative surgery if compared with the older subgroup (p < .01).

In elderly women, adjuvant RT reduced the IBR, but did not improve OS.

Radical cystectomy (RC) is the main treatment option for patients with muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC), which carry the highest risk of progression. In this study, we investigated the effect of time from transurethral resection of the bladder (TUR-B) to cystectomy on lymph node positivity, cancer-specific survival and overall survival in patients with MIBC.

The records were reviewed of 530 consecutive patients who had RC and pelvic lymphadenectomy procedures with curative intent performed by selected surgeons between May 2005 and April 2016. Our analysis included only patients with transitional cell carcinoma of the bladder; we excluded 23 patients with other types of tumor histology.

Patients who underwent delayed RC were compared with patients who were treated with early RC; both groups were similar in terms of age, gender, T stage, tumor grade, tumor differentiation, lymph node status and metastasis status. However, when both groups were compared for disease-free survival and overall survival, patients of the early-RC group had a greater advantage.

The optimal time between the last TUR-B and RC is still controversial. A reasonable time for preoperative preparation can be allowed, but long delays, especially those exceeding 3 months, can lead to unfavorable outcomes in cancer control.

In the last decade contrast-enhanced magnetic resonance imaging (MRI) has gained a growing role as a complementary tool for breast cancer diagnosis. Currently the relationship between the kinetic features of a breast lesion and pathologic prognostic factors has become a popular field of research. Our aim is to verify whether breast MRI could be considered a useful tool to predict Ki-67 score, thus resulting as a breast cancer prognosis indicator.

From June to December 2014, we enrolled patients with breast cancer who underwent preoperative dynamic contrast-enhanced MRI at the local health agency. We analyzed the time-signal intensity curves calculating the mean values of the following parameters: the basal enhancement (E_base), the enhancement ratio (ENH_ratio), the maximum enhancement (E_max), and the steepest slope of the contrast enhancement curve (S_max). Scatterplots and Pearson correlation test were used to investigate the eventual associations among these parameters.

A total of 27 patients underwent breast MRI during the study period. The mean ± SD Ki-67 percentage was 27.03 ± 16.8; the mean E_max, S_max, E_base, and ENH_ratio were 433.9 ± 120.2, 267.3 ± 96.8, 165.5 ± 77.1, and 187.1 ± 94.8, respectively. Scatterplots suggest a positive correlation between Ki-67 and both E_max and S_max. The correlation tests between Ki-67 and E_max, Ki-67 and S_max showed statistical significance.

Our preliminary data suggest that enhancement pattern is closely linked to breast cancer proliferation, thus proving the relationship between more proliferating tumors and more rapidly enhanced lesions. This is hypothesis-generating for further studies aimed at promoting breast MRI in the early estimation of cancer prognosis and tumor in vivo response to chemotherapy.

The primary objective of our study was to examine the clinical outcomes and prognosis of patients with metastatic renal cell carcinoma (mRCC) with brain metastases (BMs) receiving targeted therapy.

Fifty-eight patients from 16 oncology centers for whom complete clinical data were available were retrospectively reviewed.

The median age was 57 years (range 30-80). Most patients underwent a nephrectomy (n = 41; 70.7%), were male (n = 42; 72.4%) and had clear-cell (CC) RCC (n = 51; 87.9%). Patients were treated with first-line suni-tinib (n = 45; 77.6%) or pazopanib (n = 13; 22.4%). The median time from the initial RCC diagnosis to the diagnosis of BMs was 9 months. The median time from the first occurrence of metastasis to the development of BMs was 7 months. The median overall survival (OS) of mRCC patients with BMs was 13 months. Time from the initial diagnosis of systemic metastasis to the development of BMs (<12 months; p = 0.001), histological subtype (non-CC; p<0.05) and number of BMs (>2; p<0.05) were significantly associated with OS in multivariate analysis. There were no cases of toxic death. One mRCC patient with BMs (1.7%) experienced treatment-related cerebral necrosis. All other toxicities included those commonly observed with VEGF-TKI therapy.

The time from the initial diagnosis of systemic metastasis to the development of BMs (<12 months), a non-CC histological subtype, and a greater number of BMs (>2) were independent risk factors for a poor prognosis.

The aim of this work was to investigate the predictive factors for bladder cancer recurrence survival (BCRS) in patients with upper-tract urothelial carcinoma (UTUC).

We selected patients with UTUC who underwent segmental ureterectomy (Su) or nephroureterectomy (Nu) from 2004 to 2013 from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with a history of intravesical therapy for bladder cancer and bladder cancer prior to the diagnosis of UTUC were excluded. We used Kaplan-Meier analysis, log-rank tests, and Cox proportional hazards model to compare overall survival, cancer-specific survival, and BCRS.

In a cohort of 1,454 patients, 169 (11.6%) had low-grade tumors and 1,285 (88.4%) had high-grade tumors; 239 (16.4%) underwent Su and 1,215 (83.6%) underwent Nu. We found that T4 grade (hazard ratio [HR] = 6.216; 95% confidence interval [CI], 3.197-12.087) and ureteral tumors (HR = 1.764; 95% CI, 1.173-2.652) were predictors of shorter BCRS, whereas Nu (HR = 0.608; 95% CI, 0.388-0.953) predicted longer BCRS. Five-year BCRS rates were low-grade tumors: 94.1%, high-grade tumors: 85.4% (p = 0.038); plus Su: 82.9%, and Nu: 87.6% (p = 0.016).

Use of Su should be more selective for high-grade tumors, as it correlates with shorter BCRS. Tumors located in the ureter are associated with shorter BCRS than those located in the renal pelvis.

To assess the contribution of Italian radiation oncologists in the current management of recurrent high-grade gliomas (HGG), focusing on a reirradiation (reRT) approach.

In 2015, the Reirradiation and the Central Nervous System Study Groups on behalf of the Italian Association of Radiation Oncology (AIRO) proposed a survey. All Italian radiation oncologists were individually invited to complete an online questionnaire regarding their clinical management of recurrent HGG, focusing on a reRT approach.

A total of 37 of 210 questionnaires were returned (18% of all centers): 16 (43%) from nonacademic hospitals, 14 (38%) from academic hospitals, 5 (13%) from private institutions, and 2 (6%) from hadron therapy centers. The majority of responding centers (59%) treated ≤5 cases per year. Performance status at the time of recurrence, along with a target diameter <5 cm and an interval from primary radiation ≥6 months, were the prevalent predictive factors considered for reRT. Sixty percent of reirradiated patients had already received a salvage therapy, either chemotherapy (40%) or reoperation (20%). The most common approach for reRT was fractionated stereotactic radiotherapy to a mean (photon) dose of 41.6 Gy.

Although there were wide variations in the clinical practice of reRT across the 37 centers, the core activities were reasonably consistent. These findings provide a basis for encouraging a national collaborative study to develop, implement, and monitor the use of reRT in this challenging clinical setting.

High-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) is used to treat patients with relapsed Hodgkin’s lymphoma. In this retrospective study we report our experience with patients who underwent HDCT and ASCT.

All patients ≥15 years old with relapsed/refractory Hodgkin’s lymphoma who underwent HDCT and ASCT between June 2001 and December 2013 were included.

Fifty-four patients were identified. Median age at transplant was 22 years (range 15-49 years); 26 were men and 28 were women. Forty-eight patients (89%) underwent HDCT and ASCT after achieving a radiological response to salvage chemotherapy. The rate of radiological complete response to salvage chemotherapy was 13% and reached 50% within 3 months of ASCT in assessable patients. After a median follow-up of 25 months, 31 patients (57%) were still alive with no evidence of relapse or progression. Median event-free survival (EFS) was 24 months (95% CI 8.7-39.3) and 3-year EFS was 56%. Median overall survival (OS) was not reached and 3-year OS was 82.5%. Bulky mediastinal disease at relapse, hemoglobin level, and number of salvage regimens did not significantly impact EFS in univariate and multivariate analyses. After transplantation there was a trend towards longer EFS (30 vs. 24 months; p = 0.36) in patients with a longer time from the end of first-line treatment until relapse (≥12 vs. <12 months). The 100-day transplant-related mortality was 5.5%.

HDCT and ASCT for relapsed/refractory Hodgkin’s lymphoma is safe. Our findings are consistent with published phase III results. Longer follow-up is warranted.

Although sorafenib is the upfront standard of care for advanced hepatocellular carcinoma (HCC), molecular predictors of efficacy have not been identified yet. In the ALICE-1 study, rs2010963 of VEGF-A and VEGF-C proved to be independent predictive factors for progression-free survival (PFS) and overall survival (OS) in multivariate analysis. The ALICE-1 study results were confirmed in the ALICE-2 study, in which VEGF and VEGFR SNPs were analyzed. In the ePHAS study we analyzed the SNPs of eNOS. In univariate analysis, patients homozygous for an eNOS haplotype (HT1: T-4b at eNOS-786/eNOS VNTR) had significantly shorter median PFS and OS than those with other haplotypes. These data were confirmed in the validation set.

This nonpharmacological, interventional, prospective multicenter study aims to determine whether eNOS, HIF-1, VEGF, Ang2 and VEGFR polymorphisms play a role in predicting the objective response rate, PFS, and OS of advanced HCC patients treated with sorafenib. The study will involve 160 advanced HCC patients with Child-Pugh class A disease. The primary aim is to validate the prognostic or predictive roles of eNOS, Ang2, HIF-1, VEGF and VEGFR polymorphisms in relation to the clinical outcome (PFS) of HCC patients treated with sorafenib.

Overall, our data may suggest that polymorphism analysis of the VEGF, VEGFR-2, HIF and eNOS genes can identify HCC patients who are more likely to benefit from sorafenib.