Fourteen cases of mucosal melanomas of the oral cavity

Fourteen cases of mucosal melanomas of the oral cavity were treated from January, 1970 to April, 1986 in our department. The patients were 10 males and 4 females and in their fifth and sixth decades with the primary sites in the upper gingiva and palates in the majority. The 3 and 5 year survival rates were 21.4% and 14.3% respectively, with unfavorable prognosis in comparison with cutaneous melanoma. The clinical stages were as follows: stage Ia (1), Ib (8), II (5), which affected the prognosis. The depth of invasion, as described by Breslow et al., were beyond 1.50 mm except in one case, which might be a significant prognostic factor in the study of mucosal melanoma of the oral cavity. Seventy one percent had neck node metastases and 35% had distant metastases. The high occurrence of metastases might be related to their poor prognosis.     

Epidemiology and survival outcomes of ocular and mucosal melanomas: A population‐based analysis

Extracutaneous melanomas are poorly characterized tumors that include ocular (OM), mucosal (MM) and leptomeningeal melanomas, often lacking standardized staging and treatment guidelines. We analyzed cases of cutaneous melanoma (CM, N = 219,890), OM (N = 7,069) and MM (N = 2,755) of different anatomical origins, diagnosed between 1988 and 2010, recorded in the Surveillance Epidemiology and End Results (SEER) database. Relative survival was studied in patients grouped by summary stage classification (localized, regional or distant disease) and in multivariate models adjusting for varying distribution of baseline factors. Unlike in CM, the incidence rate in MM increased exponentially with age. Five‐year relative survival was significantly worse for OM (78%) and for most mucosal sites (aggregate 34%, range 3–69%) compared with CM (89%). The differences between primary sites were particularly pronounced in localized disease, with a hazard ratio of 5.7 for OM, 4.3–9.0 for external genital or oral cavity MM and 19.8–90.4 for other mucosal locations. Melanomas of the pharynx, gastrointestinal, urinary tract and vagina had poor outcomes regardless of clinical stage. In contrast to CM, there was no evidence of improved survival in OM and MM during the study period. A substantial proportion of patients with operable OM or MM underwent radical organ resections (13–88% depending on site and stage) or perioperative radiotherapy (0–66%). In conclusion, extracutaneous melanomas have a markedly worse survival than CM and aggressive locoregional management appears to be insufficient for their control. Because of poor outcomes in MM, studies of systemic therapy are warranted regardless of the extent of disease at presentation.     

Metastatic melanoma of unknown primary resembles the genotype of cutaneous melanomas

BackgroundAlthough 90% of all melanomas are of cutaneous origin, some patients present with melanoma metastases of unknown origin (MUP). Commonly, in these patients an extensive search for the primary tumor is carried out. In the past, genetic analyses have shown substantial differences in pathogenetic mutations among cutaneous, acral and mucosal melanomas. The aim of this study was to assess the mutational status of MUP in order to better characterize the putative origin of the primary tumor and to evaluate potential prognostic factors.Patients and methodsThe medical records of 44 patients with MUP were analyzed and a survival analysis was conducted. In total, 66 paraffin samples of 44 patients were analyzed, and in 15 patients multiple metastases were tested. Mutational analysis of the BRAF, NRAS and KIT genes was carried out.ResultsTwenty-three patients (52.3%) had a mutation in the BRAF gene and 12 patients (23.8%) had a mutation in the NRAS gene. There were neither mutations in the KIT gene. In patients with multiple samples, there was 100% consistency regarding mutational status among the different metastases. The median overall survival (OS) was 86.4 months (39–134). The American Joint Committee on Cancer stage at first diagnosis of metastatic melanoma (stage III versus IV) was significantly associated with OS (P < 0.001), BRAF or NRAS mutation status had no significant prognostic impact on clinical outcomes.ConclusionsMUP resembles the genotype of cutaneous melanoma and not that of mucosal melanomas.     

Molecular characterization of a selected cohort of patients affected by pulmonary metastases of malignant melanoma: Hints from BRAF,NRAS and EGFR evaluation

Background

Melanoma is highly curable in early stages but holds devastating consequences in advanced phases with a median survival of 6–10 months. Lungs are a common metastasis target, but despite this, limited data are available on the molecular status of pulmonary lesions.

Materials and Methods

25 patients with surgically resected melanoma lung metastases were screened for BRAF, NRAS, CKIT and EGFR alterations. The results were correlated with time to lung metastasis (TLM), relapse-free survival after metastasectomy (RFS) and overall survival (OS).

Results

BRAF or NRAS were mutated in 52% and 20% of cases while CKIT was unaffected. Chromosome 7 polysomy was detected in 47% of cases with 17.5% showing EGFR amplification and concomitant BRAF mutation. NRAS mutated patients developed LM within 5 yrs from primary melanoma with larger lesions compared with BRAF (mean diameter 3.3 ± 2.2cm vs 1.9 ± 1.1cm, p = 0.2). NRAS was also associated with a shorter median RFS and OS after metastasectomy. Moreover, Cox regression analysis revealed that NRAS mutation was the only predictive factor of shorter survival from primary melanoma (p = 0.039, OR = 5.5 (1.1–27.6)).

Conclusions

Molecular characterization identifies advanced melanoma subgroups with distinct prognosis and therapeutic options. The presence of NRAS mutation was associated to a worse disease evolution.     

Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer

BACKGROUND:

It is hypothesized that BRAF mutant cancers represent a discrete subset of metastatic colorectal cancer (CRC) defined by poorer survival. This study investigates whether BRAF mutant CRC is further defined by a distinct pattern of metastatic spread and explores the impact of BRAF mutation and microsatellite instability (MSI) on prognosis in metastatic CRC.

METHODS:

By using prospective clinical data and molecular analyses from 2 major centers (Royal Melbourne Hospital and The University of Texas MD Anderson Cancer Center), patients with known BRAF mutation status were analyzed for clinical characteristics, survival, and metastatic sites.

RESULTS:

The authors identified 524 metastatic CRC patients where BRAF mutation status was known; 57 (11%) were BRAF mutant tumors. BRAF mutant tumors were significantly associated with right‐sided primary tumor, MSI, and poorer survival (median, 10.4 months vs 34.7 months, P < .001). A distinct pattern of metastatic spread was observed in BRAF mutant tumors, namely higher rates of peritoneal metastases (46% vs 24%, P = .001), distant lymph node metastases (53% vs 38%, P = .008), and lower rates of lung metastases (35% vs 49%, P = .049). In additional survival analyses, MSI tumors had significantly poorer survival compared with microsatellite stable tumors (22.1 months vs 11.1 months, P = .017), but this difference was not evident in the BRAF mutant population.

CONCLUSIONS:

The pattern of metastatic spread observed in this study further defines BRAF mutant CRC as a discrete disease subset. The authors demonstrated that, unlikely early stage disease, MSI is associated with poorer survival in metastatic CRC, although this is driven by its association with BRAF mutation. Cancer 2011;. © 2011 American Cancer Society.     

Melanoma of unknown primary origin: A population-based study in the Netherlands

AimFew population-based studies have been published on melanoma of unknown primary origin (MUP). This study’s aim is to describe characteristics and survival of MUP patients in the Netherlands, based on nationwide data from the Netherlands Cancer Registry (NCR).MethodsPatient and tumour characteristics of MUP patients were retrieved from the NCR. Subgroups were made according to metastatic site: nodal or distant. Survival rates were calculated using the Kaplan–Meier method. To obtain a better insight in the composition and prognosis of the MUP group, the survival was compared to that of patients with melanoma of a known primary origin (MKP), tumour-node-metastasis (TNM) stage III and IV.ResultsOf all 33,181 melanoma patients diagnosed between 2003 and 2009, 2.6% (n = 857) were diagnosed with MUP. MUP patients with nodal metastases had a similar survival as MKP stage III with macroscopic nodal involvement. After stratification according to the number of involved lymph nodes, the survival of patients with nodal metastases with one involved lymph node was not significantly different between MUP and MKP. The survival of MUP patients with two or more involved lymph nodes was slightly worse than that of MKP stage III patients with macroscopic nodal involvement with two or more involved lymph nodes. MUP patients with distant metastases had a similar survival as MKP stage IV. After stratification according to number of metastatic sites and metastatic site category, the survival in MKP stage IV patients with (sub)cutaneous metastases was slightly worse than MUP distant patients with (sub)cutaneous metastases.ConclusionsThe results of this study imply that MUP patients form a heterogeneous group, and that MUP patients with nodal metastases could be classified as stage III melanoma with macroscopic nodal involvement, and MUP patients with distant metastases as stage IV melanoma.     

Results of a surgical resection for patients with stage IV non--small-cell lung cancer

PurposeThis study retrospectively investigated the clinical significance of surgical treatment for stage IV non–small-cell lung cancer (NSCLC).SubjectsThere were 36 patients who underwent surgical resection for stage IV NSCLC between 1999 and 2008.ResultsThe patients included 22 males and 14 females. All patients had either synchronous distant metastasis or pleural dissemination. The mean age of the patients was 65.8 years (range, 18 to 90 years). The histological types included 29 adenocarcinomas, 5 squamous-cell carcinomas and 2 large-cell carcinomas. The organs of metastasis were bone in 5 patients, brain in 4, adrenal gland in 4, axillary lymph nodes in 3, liver in 2, and 1 patient had a contralateral pulmonary metastasis. The number of metastases was one site in 13, two sites in 3, three sites in 1, and five sites in 2 patients. The patients with bone metastasis were treated with radiation, and the patients with brain metastasis underwent stereotaxic radiosurgery. The patients with either adrenal metastasis, axillary lymph node metastasis, or contralateral lung metastasis underwent surgical resection. Among the patients with distant metastasis, the 5-year survival rate was 30.1 %. There were 17 patients with pleural dissemination. The 5-year survival rate in these patients was 25.3%. The overall 5-year survival rate after surgery in the patients with stage IV disease was 26.8%.ConclusionSelected patients who can undergo surgical resection for the primary tumor and effective local therapy for metastatic lesions still have a chance to obtain long-term survival. Surgical treatment for NSCLC with oligometastatic disease can be considered as one arm of multidisciplinary treatment.     

Malignant mucosal melanoma of the head and neck — a review

Mucosal melanomas comprise about 1% of all malignant melanomas and exhibit far more aggressive behaviour than that of skin melanomas: they are more inclined to metastatize into regional and distant sites or recur locally, regionally or in distant locations, resulting in a high rate of cause-specific death. Mucosal melanomas in the head and neck region account for half of all mucosal melanomas, occurring mainly in the upper respiratory tract, oral cavity and pharynx. They appear with equal gender distribution and with a peak incidence in the age range 60-80 years. In consequence of their hidden location, they are usually diagnosed in a locoregionally advanced clinical stage, with a rate of 5-48% of regional and 4-14% of distant dissemination. The typical therapeutic approach is surgery, postoperative irradiation and systemic therapy. Local control with either surgery or radiotherapy is frequently (60- 70%) achieved, but the rates of local, regional and distant recurrences are high (50-90%, 20-60% and 30-70%, respectively). The reported 5-year actual survival rates are poor (17-48%), which is attributed mainly to a haematogenous dissemination. These characteristics demonstrate that identification of the precursor lesions and more effective local and systemic approaches are needed to improve the therapeutic results.     

Clinical outcomes of melanoma brain metastases treated with stereotactic radiosurgery and anti-PD-1 therapy,anti-CTLA-4 therapy,BRAF/MEK inhibitors,BRAF inhibitor,or conventional chemotherapy

Novel targeted and immunotherapeutic agents have revolutionized systemic melanoma management. We note differing rates of distant brain control as well as overall survival following systemic treatment and stereotactic radiosurgery (SRS) in melanoma brain metastases management. These data support further research to determine the potential synergistic effect between these agents with SRS.BackgroundThe effect of immunologic and targeted agents on intracranial response rates in patients with melanoma brain metastases (MBMs) is not yet clearly understood. This report analyzes outcomes of intact MBMs treated with single-session stereotactic radiosurgery (SRS) and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors(i), BRAFi, or conventional chemotherapy.Patients and methodsPatients were included if MBMs were treated with single-session SRS within 3 months of receiving systemic therapy. The primary end point of this study was distant MBM control. Secondary end points were local MBM control defined as a >20% volume increase on follow-up MRI, systemic progression-free survival, overall survival (OS) from both SRS and cranial metastases diagnosis, and neurotoxicity. Images were reviewed alongside two neuro-radiologists at our institution.ResultsNinety-six patients were treated to 314 MBMs over 119 SRS treatment sessions between January 2007 and August 2015. No significant differences were noted in age (P = 0.27), gender (P = 0.85), treated gross tumor volume (P = 0.26), or the diagnosis-specific graded prognostic assessment (P = 0.51) between the treatment cohorts. Twelve-month Kaplan–Meier (KM) distant MBM control rates were 38%, 21%, 20%, 8%, and 5% (P = 0.008) for SRS with anti-PD-1 therapies, anti-CTLA-4 therapy, BRAF/MEKi, BRAFi, and conventional chemotherapy, respectively. No significant differences were noted in the KM local MBM control rates among treatment groups (P = 0.25). Treatment with anti-PD-1 therapy, anti-CTLA-4 therapy, or BRAF/MEKi significantly improved OS on both univariate and multivariate analyses when compared with conventional chemotherapy.ConclusionIn our institutional analysis of patients treated with SRS and various systemic immunologic and targeted melanoma agents, significant differences in distant MBM control and OS are noted. Prospective evaluation of the potential synergistic effect between these agents and SRS is warranted.     

Early Distant Recurrence in Patients With Resected Stage I Lung Cancer: A Case Series of “Blast Metastasis”

BackgroundThe standard of care in the management of stage I non–small-cell lung cancer (NSCLC) has been anatomic lung resection with multistation lymph node sampling of ≥ 10 lymph nodes. The 5-year survival for NSCLC has ranged from 73% to 93% (for stage IB and stage IA, respectively) and will be more favorable for patients with fewer comorbidities and those with a higher state of premorbid functioning and who undergo surgical resection. Despite the positive prognosis for operable stage I NSCLC, a subset of patients will develop metastatic disease within as few as 12 months after resection. Using an institutional database, we have presented the data from 68 patients who had developed distant metastatic recurrence after resection of pathologic stage I NSCLC within 1 year after surgery.Patients and MethodsA retrospective study was conducted of a prospectively maintained intuitional database. The final cohort included patients with pathologic stage I NSCLC who had undergone anatomic resection but had subsequently presented with multiple sites of distant recurrence within 1 year. The study period extended from 2003 to 2020. Patients with broad local recurrence or recurrence at a single distant site were excluded. Kaplan-Meier analysis was used to estimate the 5-year survival.ResultsA total of 2827 patients had undergone surgical resection for stage I NSCLC during the 17-year period and 68 met the criteria for inclusion. Most of the patients (n = 48) were smokers, and the dominant histologic type was adenocarcinoma (n = 37). After recurrence, 22 patients (33%) had undergone chemoradiotherapy and 19 (28%) had received chemotherapy alone. The mean and median overall survival were 23.7 and 14 months, respectively. The 5-year survival from recurrence and surgery were both 13.2%.ConclusionsLimited data are available on the risk factors for early metastasis after resected stage I NSCLC. The results from our cohort have demonstrated poor survival after recurrence. These data might be the basis for determining a phenotype for patients prone to early widespread metastasis despite seemingly curative surgical resection.     

Construction and evaluation of prognostic models for esophageal cancer patients with distant and non-distant metastases: providing a reference process for clinical diagnosis and treatment

BackgroundAlthough the current treatment for esophageal cancer has great technological progress, the 5-year survival rate of patients is not optimistic. About 70% of patients with esophageal cancer are at an advanced stage at first diagnosis. These patients are prone to distant metastasis, and the prognosis is poor. Therefore, understanding the risk factors for distant metastasis in patients with esophageal cancer, combined with the prognosis of the patient, can aid in choosing the optimal diagnosis and treatment plan. Ultimately, it will improve the patient’s survival time and quality of life. This research aims to construct a model for the risk assessment of distant metastasis in patients with esophageal cancer and prognostic models for patients with distant and non-distant metastases.MethodsThe Surveillance Epidemiology and End Results (SEER) database was used to select patients with esophageal cancer from 2010 to 2015. The optimal cutoff point was selected for the age and tumor size variables using X-tile. The nomogram was constructed using R software (The R Foundation for Statistical Computing).ResultsGender, grade, T stage, N stage, and tumor size were independent risk factors associated with distant metastasis in patients with esophageal cancer. The concordance index (C-index) of the nomogram prediction model for whether the patient will have distant metastasis was 0.609. Age, grade, T stage, N stage, and tumor size were independent risk factors affecting the prognosis without distant metastasis. The C-index of the nomogram prediction model for patients with distant metastases was 0.590. Age and T stage were independent risk factors affecting the prognosis of patients with distant metastases. The C-index of the nomogram prediction model was 0.543. The combination of radiotherapy, chemotherapy, and primary surgery yielded the best overall survival for both patients with distant metastases and patients with non-distant metastases.ConclusionsA comprehensive assessment of the risk of distant metastasis in patients with esophageal cancer, combined with prognosis prediction, is necessary to provide patients with a reasonable treatment plan.     

Anal carcinoma – Survival and recurrence in a large cohort of patients treated according to Nordic guidelines

ObjectiveTo evaluate treatment outcome in a large population-based cohort of patients with anal cancer treated according to Nordic guidelines.MaterialClinical data were collected on 1266 patients with anal squamous cell carcinoma diagnosed from 2000 to 2007 in Sweden, Norway and Denmark. 886 of the patients received radiotherapy 54–64 Gy with or without chemotherapy (5-fluorouracil plus cisplatin or mitomycin) according to different protocols, stratified by tumor stage.ResultsHigh age, male gender, large primary tumor, lymph node metastases, distant metastases, poor performance status, and non-inclusion into a protocol were all independent factors associated with worse outcome. Among patients treated according to any of the protocols, the 3-year recurrence-free survival ranged from 63% to 76%, with locoregional recurrences in 17% and distant metastases in 11% of patients. The highest rate of inguinal recurrence (11%) was seen in patients with small primary tumors, treated without inguinal irradiation.ConclusionsGood treatment efficacy was obtained with Nordic, widely implemented, guidelines for treatment of anal cancer. Inguinal prophylactic irradiation should be recommended also for small primary tumors.     

The impact of pelvic retroperitoneal invasion and distant nodal metastases in epithelial ovarian cancer

BackgroundThe absence of disease after debulking surgery is the most important prognostic factor in the treatment of advanced epithelial ovarian cancer (EOC). Occasionally, the presence of extra-abdominal disease complicates the ability to obtain a complete surgery, considering some locations of the metastatic disease as unresectable. The objective of the study was to estimate the survival impact of pelvic retroperitoneal invasion and extrapelvic and aortic distant nodal metastases in EOC patients. The anatomical landmarks of primary cytoreductive surgery will be discussed.Material and methodsWe reviewed data from 116 consecutive Mayo Clinic patients with epithelial ovarian cancer (EOC) stage IIIC and IV, undergoing primary cytoreduction surgery between 1996 and 2000. Univariate and multivariate analysis for patients with positive distant nodes and pelvic retroperitoneal invasion was performed, including 57 patients with no residual disease after surgery. Kaplan–Meier curves were used to estimate the probability of survival.ResultsThe median patient's age was 65 years (range 24–87 years). The 5 years overall survival was 44.8% (range 30.1–57.9 months) and the median length of survival was 39.9 months (range 0.13–60 months, 95% confidence interval: 30.1–57.9). Pelvic retroperitoneal invasion was present in 22 EOC patients (18.9%) and distant positive nodes were noted in 11 (9.5%): suprarenal/celiac (5.2%), inguinal (4.3%) and supraclavicular (0.9%). Univariate and multivariate Cox regression analysis, identified distant positive lymph nodes and pelvic retroperitoneal invasion as factors statistically associated with overall survival (p = 0.002 and p = 0.025, respectively).ConclusionsMetastatic distant nodes and pelvic retroperitoneal invasion are independent prognostic factors for survival in patients with advanced EOC.     

Whole-genome sequencing reveals complex mechanisms of intrinsic resistance to BRAF inhibition

BackgroundBRAF is mutated in ∼42% of human melanomas (COSMIC. http://www.sanger.ac.uk/genetics/CGP/cosmic/) and pharmacological BRAF inhibitors such as vemurafenib and dabrafenib achieve dramatic responses in patients whose tumours harbour BRAF^V600 mutations. Objective responses occur in ∼50% of patients and disease stabilisation in a further ∼30%, but ∼20% of patients present primary or innate resistance and do not respond. Here, we investigated the underlying cause of treatment failure in a patient with BRAF mutant melanoma who presented primary resistance.MethodsWe carried out whole-genome sequencing and single nucleotide polymorphism (SNP) array analysis of five metastatic tumours from the patient. We validated mechanisms of resistance in a cell line derived from the patient's tumour.ResultsWe observed that the majority of the single-nucleotide variants identified were shared across all tumour sites, but also saw site-specific copy-number alterations in discrete cell populations at different sites. We found that two ubiquitous mutations mediated resistance to BRAF inhibition in these tumours. A mutation in GNAQ sustained mitogen-activated protein kinase (MAPK) signalling, whereas a mutation in PTEN activated the PI3 K/AKT pathway. Inhibition of both pathways synergised to block the growth of the cells.ConclusionsOur analyses show that the five metastases arose from a common progenitor and acquired additional alterations after disease dissemination. We demonstrate that a distinct combination of mutations mediated primary resistance to BRAF inhibition in this patient. These mutations were present in all five tumours and in a tumour sample taken before BRAF inhibitor treatment was administered. Inhibition of both pathways was required to block tumour cell growth, suggesting that combined targeting of these pathways could have been a valid therapeutic approach for this patient.     

The effect of locoregional recurrence on survival and distant metastasis after conservative treatment for invasive breast carcinoma

AimsPatients with invasive breast cancer submitted to conservative treatment must be followed for a long period of time to study locoregional control. In this study, we analysed the outcome and relationships between locoregional recurrence (LRR), distant metastases and survival.Materials and methodsA 15-year study, including 470 women with early breast cancer, stage I and II, who underwent breast conservative treatment. Tumour size, nodal status, age, menopausal status, histological grade and LRR were analysed for their ability to predict overall survival, disease-specific survival and distant disease-free survival.ResultsWith a median follow-up time of 6.6 years (3 months to 19.1 years), there were 19 LRR at their first site of recurrence and 53 distant metastases. Tumour size greater than 2 cm, positive lymph nodes and histological grade III were significantly related to lower overall and distant metastases-free survival. On multivariate analysis, nodal status, histological grade III and LRR (coded as a time-dependent variable) were significantly related to overall, specific and distant metastases-free survival, whereas tumour size had only a borderline effect on specific and distant disease-free survival. Landmark analysis showed that women who presented an LRR within 2 years after surgery had significantly lower distant disease-free survival (hazard ratio [HR]: 8.39; 95% CI 2.56–27.47; P < 0.001), specific survival (HR: 8.19; 95% CI 2.45–27.41; P < 0.001) and overall survival (HR: 6.02; 95% CI 2.25–16.11; P < 0.005).ConclusionsLRR seems to be a significant predictor of distant metastases and survival, and patients who sustain early LRR tend to display a more aggressive clinical course.     

The role of surgery for locally recurrent and second recurrent rectal cancer with metastatic disease

BackgroundThe role of surgery for locally recurrent rectal cancer (LRRC) with resectable distant metastases or second LRRC remains unclear. This study aimed to clarify the influence of synchronous distant metastases (SDMs), a history of distant metastasis resection (HDMR), and a second LRRC on the outcome.MethodsThe long-term outcomes of 70 surgically treated patients with LRRC between 2006 and 2018 were compared by SDM (n = 10), HDMR (n = 17), and second LRRC (n = 7).ResultsAmong the 10 patients with SDM, 4 patients underwent simultaneous resection, whereas the other 6 underwent staged resection with distant first approach. Recurrence developed in 9 patients, of which 2 patients with liver re-resection achieved long-term survival without cancer. The patients with and without SDM had equivalent 5-year overall survival rate (40.5% vs. 53.3%, p = 0.519); however, patients with SDM had a worse 3-year recurrence-free survival rate than those without SDM (10.0% vs. 37.5%, p = 0.031). Multivariate analysis showed that primary non-sphincter-preserving surgery, second LRRC, and R1 resection were independent risk factors for overall survival. Similarly, primary non-sphincter-preserving surgery, second LRRC, SDM, and R1 resection were risk factors for recurrence-free survival.ConclusionsPatients with SDM might still be suitable to undergo salvage surgery and achieve favourable overall survival. Distant metastasectomy should be performed first, followed by a sufficient interval to avoid unnecessary LRRC resection in uncurable patients. An HDMR should not be taken into consideration when making surgical plans. Surgical indication of second LRRC should be strict, especially in referred patients.     

Moderately Hypofractionated Radiotherapy and Androgen Deprivation Therapy for High-risk Localised Prostate Cancer: Predictors of Long-term Biochemical Control and Toxicity

AimsThere is a paucity of long-term data on outcomes of high-risk prostatic adenocarcinoma after moderately hypofractionated radiotherapy with elective nodal treatment and long-term androgen deprivation therapy (ADT). We report long-term control and toxicity outcomes and analyse the predictors of failure and toxicity.Materials and methodsThe records of 120 consecutive high-risk prostate cancer patients treated in a single institution between February 2012 and December 2016 were retrospectively analysed. A moderately hypofractionted radiotherapy (HypoRT) regimen of 60 Gy in 20 fractions over 4 weeks with simultaneous elective pelvic irradiation to 44 Gy in 20 fractions with intensity-modulated radiotherapy was used, together with long-term ADT with either orchiectomy or medical castration for a total duration of 2–3 years. We analysed biochemical control, metastasis-free survival and late toxicities and their predictive factors using survival analysis.ResultsPatients had locally advanced cancers (cT3 77.5%, median pretreatment prostate-specific antigen 30 ng/ml, Gleason score 8–10 in 45.8%). The median follow-up time was 70 months. The 3- and 5-year probability of freedom from biochemical progression was 93% and 80%, respectively. The 5-year probability of freedom from local relapse/intra-pelvic nodal relapse/distant metastases as the site of first failure was 96%/97%/86%, respectively. Gleason score 8–10 and medical ADT for 2–3 years (as opposed to orchidectomy) were independent risk factors for distant metastases. A total of 18 grade 2 and above late gastrointestinal toxicity events and a total of 23 grade 2 and above late genitourinary toxicity events were documented. Patients who underwent a transurethral resection of prostate prior to radiotherapy had worse urological toxicity.ConclusionsHypoRT with elective nodal treatment results in excellent pelvic control. Distant metastases are the primary mode of failure. Risk of metastases is associated with Gleason score and the duration of ADT. Late urinary toxicities are more common in those with prior transurethral resection of prostate.     

Surgical therapy for distant metastases of malignant melanoma

BACKGROUND: Manifestation of distant metastases in melanoma patients commonly indicates a poor prognosis. The aim of the current study was to examine the role of surgical treatment in these patients. METHODS: Data from 444 patients with distant melanoma metastases were gathered prospectively from January 1978 through December 1997. Characteristics of the primary tumor, time until the first occurrence of distant metastases, frequency and site of distant metastases, surgical therapy, and survival were evaluated by univariate and multivariate analyses. RESULTS: Histology, Breslow thickness, Clark level, and pT and pN categories (UICC 1997) significantly influenced the median interval from initial diagnosis to manifestation of distant metastases. The most common single localization was the lung (n = 83), followed by distant lymph node (n = 79), and skin metastases (n = 51). One hundred seventy-four patients received surgical treatment (39%) and 111 (25%) patients received surgical treatment with curative resection (R0, UICC 1997), most frequently in distant lymph node or skin metastases (57% and 59%, respectively). Median survival time and 2-year survival rate for all patients were 7 months and 15.8%, respectively, 17 months and 36.1% following curative resection, 6 months and 12.7% after incomplete resection (n = 63) (P < 0.0001). Conservatively treated patients survived for a median of only 4 months with a 2-year survival of 8.1%. Multivariate survival analysis showed localization of the primary tumor (head/neck/trunk vs. extremities), the number of involved sites, and surgical therapy to be independent prognostic factors. CONCLUSIONS: Surgical therapy of distant metastases was most beneficial when complete removal of metastatic tissue was achieved. Selection of patients for surgical excision should be determined by individual patient indications.     

Evaluation of short-course radiotherapy followed by neoadjuvant bevacizumab,capecitabine, and oxaliplatin and subsequent radical surgical treatment in primary stage IV rectal cancer

BackgroundTo evaluate the efficacy and tolerability of preoperative short-course radiotherapy followed by capecitabine and oxaliplatin treatment in combination with bevacizumab and subsequent radical surgical treatment of all tumor sites in patients with stage IV rectal cancer.Patients and methodsAdults with primary metastasized rectal cancer were enrolled. They received radiotherapy (5 × 5 Gy) followed by bevacizumab (7.5 mg/kg, day 1) and oxaliplatin (130 mg/m², day 1) intravenously and capecitabine (1000 mg/m² twice daily orally, days 1–14) for up to six cycles. Surgery was carried out 6–8 weeks after the last bevacizumab dose. The percentage of radical surgical treatment, 2-year survival and recurrence rates, and treatment-related toxicity was evaluated.ResultsOf 50 included patients, 42 (84%) had liver metastases, 5 (10%) lung metastases, and 3 (6%) both liver and lung metastases. Radical surgical treatment was possible in 36 (72%) patients. The 2-year overall survival rate was 80% [95% confidence interval (CI) 66.3%–90.0%]. The 2-year recurrence rate was 64% (95% CI 49.8%–84.5%). Toxic effects were tolerable. No treatment-related deaths occurred.ConclusionsRadical surgical treatment of all tumor sites carried out after short-course radiotherapy, and bevacizumab–capecitabine–oxaliplatin combination therapy is a feasible and potentially curative approach in primary metastasized rectal cancer.