Spatial Distribution of Recurrence and Long-Term Toxicity Following Dose Escalation to the Dominant Intra-Prostatic Nodule for Intermediate-High-Risk Prostate Cancer: Insights from a Phase I/II Study.

Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intra-prostatic nodule (DIN). Materials and methods: In 33 patients with intermediate-high-risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and 68Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25-74% for partial overlap, were assessed. Long-term toxicity is reported. Results: All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17-76 months), affecting 13 out of 33 patients (39.4%). Intra-prostatic recurrences occurred in 7 patients (21%), with ≥75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patients. Notably, five patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intra-prostatic recurrences. Extended follow-up revealed late grade ≥ 2 GU and GI toxicity in 18% (n = 6) and 6% (n = 2) of the patients. Conclusions: Among patients with intermediate-high-risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: Focal dose-escalated prostate SBRT prevented recurrences in the dominant nodule; however, extra-prostatic recurrence sites were frequent.

Pattern of recurrence after stereotactic body radiotherapy of nodal lesions: a single-institution analysis.

OBJECTIVES: Stereotactic body radiotherapy (SBRT) and/or single fraction stereotactic body radiosurgery (SRS) are effective treatment options for the treatment of oligometastatic disease of lymph nodes. Despite the encouraging local control rate, progression-free survival remains unfair due to relapses that might occur in the same district or at other sites. The recurrence pattern analysis after nodal local ablative RT (laRT) in oligometastatic patients is presented in this study. METHODS: The pattern of failure of patients with nodal metastases who were recruited and treated with SBRT in the Destroy-1 or SRS in the Destroy-2 trials was investigated in this single-institution, retrospective analysis. The different relapsed sites following laRT were recorded. RESULTS: Data on 190 patients who received SBRT or SRS on 269 nodal lesions were reviewed. A relapse rate of 57.2% (154 out of 269 nodal lesions) was registered. The pattern of failure was distant in 88 (57.4%) and loco-regional in 66 (42.6%) patients, respectively. The most frequent primary malignancies among patients experiencing loco-regional failure were genitourinary and gynaecological cancers. Furthermore, the predominant site of loco-regional relapse (62%) was the pelvic area. Only 26% of locoregional relapses occurred contra laterally, with 74% occurring ipsilaterally. CONCLUSIONS: The recurrence rates after laRT for nodal disease were more frequent in distant regions compared to locoregional sites. The most common scenarios for locoregional relapse appear to be genitourinary cancer and the pelvic site. In addition, recurrences often occur in the same nodal station or in a nodal station contiguous to the irradiated nodal site. ADVANCES IN KNOWLEDGE: Local ablative radiotherapy is an effective treatment in managing nodal oligometastasis. Despite the high local control rate, the progression free survival remains dismal with recurrences that can occur both loco-regionally or at distance. To understand the pattern of failure could aid the physicians to choose the best treatment strategy. This is the first study that reports the recurrence pattern of a significant number of nodal lesions treated with laRT.

Early recurrence, time-to-recurrence, and recurrence patterns: Assessing their impact on survival outcomes in head and neck squamous cell carcinoma (R/M-HNSCC) patients treated with first line platinum-based chemotherapy.

BACKGROUND: R/M-HNSCC patients typically receive 1L platinum-based chemotherapy with pembrolizumab or cetuximab. However, the outcomes for patients with early recurrence (<6 months) remain unclear due to their exclusion from most 1L studies. This study aimed to assess the impact of time-to-recurrence intervals (TTRI) and recurrence patterns on the survival of R/M-HNSCC patients. METHODS: We identified non-curable R/M-HNSCC patients at our institution from 1/2008 through 6/2020. We analyzed the outcomes of early recurrent patients who received 1L systemic treatment, with different TTRIs and recurrence patterns. RESULTS: Our study included 234 eligible patients. The majority (47%) experienced early recurrence (<6 months), while 22%, 20%, and 11% had recurrences at 6-12 months, >12 months, and de novo metastasis, respectively. The platinum-based regimen was the most commonly used chemotherapy (86%), with cetuximab and immunotherapy utilized in 3% and 5% of cases, respectively. Significant differences in PFS and OS were observed among TTRI groups. For patients with early recurrence, both platinum-doublet and monotherapy treatments significantly improved OS. Locoregional recurrence (47%) was the most common, followed by distant metastasis (22%) and both (20%). Recurrence patterns were significantly associated with OS but not with PFS. In multivariate analysis, TTRI ≥12 months significantly correlated with improved PFS (HR 0.51; p = 0.004) and OS (HR 0.58; p = 0.009), whereas recurrent pattern did not. CONCLUSION: TTRI significantly influenced the survival, while recurrence patterns did not. In our study, the retrospective design limited our ability to definitively establish whether early recurrent R/M-HNSCC patients would benefit more from platinum-doublet. Despite poor prognosis, early recurrent patients benefited from 1L systemic treatments. Given the variation in prognoses, TTRI should be considered a stratification factor in future clinical trials.

Time to first recurrence, pattern of recurrence, and survival after recurrence in endometrial cancer according to the molecular classification.

OBJECTIVE: Despite its generally favorable prognosis at primary diagnosis, recurrence of endometrial cancer remains an important clinical challenge. The aim of this study was to analyze the value of molecular classification in recurrent endometrial cancer. METHODS: This study included patients with recurrent endometrial cancer who underwent primary surgical treatment between 2004 and 2015 at the Karolinska University Hospital, Sweden and the Bern University Hospital, Switzerland (KImBer cohort) with molecular classification of the primary tumor. RESULTS: Out of 594 molecularly classified endometrial cancer patients, 101 patients experienced recurrence, consisting of 2 POLEmut, 33 MMRd, 30 p53abn, and 36 NSMP tumors. Mean age at recurrence was 71 years and mean follow-up was 54 months. Overall, median time to first recurrence was 16 months (95% CI 12-20); with the shortest median time in MMRd patients, with 13 months (95% CI 5-21). The pattern of recurrence was distinct among molecular subgroups: MMRd tumors experienced more locoregional, while p53abn cases showed more abdominal recurrences (P = .042). Median survival after recurrence was best for MMRd cases (43 months, 95% CI 11-76), compared to 39 months (95% CI 21-57) and 10 months (95% CI 7-13) for the NSMP and p53abn cases respectively (log-rank, P = .001). CONCLUSION: Molecular classification is a significant indicator of survival after recurrence in endometrial cancer patients, and patterns of recurrence differ by molecular subgroups. While MMRd endometrial cancer show more locoregional recurrence and the best survival rates after recurrence, p53abn patients experience abdominal recurrence more often and had the worst prognosis of all recurrent patients.

Patterns of recurrence according to the extent of resection in patients with IDH-wild-type glioblastoma: a retrospective study.

OBJECTIVE: In glioblastoma (GBM) patients, controlling the microenvironment around the tumor using various treatment modalities, including surgical intervention, is essential in determining the outcome of treatment. This study was conducted to elucidate whether recurrence patterns differ according to the extent of resection (EOR) and whether this difference affects prognosis. METHODS: This single-center study included 358 eligible patients with histologically confirmed isocitrate dehydrogenase (IDH)-wild-type GBM from November 1, 2005, to December 31, 2018. Patients were assigned to one of three separate groups according to EOR: supratotal resection (SupTR), gross-total resection (GTR), and subtotal resection (STR) groups. The patterns of recurrence were classified as local, marginal, and distant based on the range of radiation. The relationship between EOR and recurrence pattern was statistically analyzed. RESULTS: Observed tumor recurrence rates for each group were as follows: SupTR group, 63.4%; GTR group, 75.3%; and STR group, 80.5% (p = 0.072). Statistically significant differences in patterns of recurrences among groups were observed with respect to local recurrence (SupTR, 57.7%; GTR, 76.0%; STR, 82.8%; p = 0.036) and distant recurrence (SupTR, 50.0%; GTR, 30.1%; STR, 23.2%; p = 0.028). Marginal recurrence showed no statistical difference between groups. Both overall survival and progression-free survival were significantly increased in the SupTR group compared with the STR and GTR groups (p < 0.0001). CONCLUSIONS: In this study, the authors investigated the association between EOR and patterns of recurrence in patients with IDH-wild-type GBM. The findings not only show that recurrence patterns differ according to EOR but also provide clinical evidence supporting the hypothesized mechanism by which distant recurrence occurs.

Mapping of Recurrence Sites Following Adjuvant or Salvage Radiotherapy for Prostate Cancer Patients.

INTRODUCTION: Although salvage and adjuvant radiotherapy (RT) are effective in prostate cancer (PC) patients, 30%-40% of men will have disease progression. The objective was to describe the pattern of recurrence in PC patients with biochemical failure (BF) following postoperative RT. METHODS: We retrospectively analyzed 935 PC patients treated from 2009 to 2019 with adjuvant or salvage RT at the Institut de Cancérologie de l'Ouest. Of these, 205 (22%) developed BF of whom 166 underwent imaging. Patients with identified radiologic failure prior any specific treatment were included to determine the site of relapse categorized as local (L)-only, locoregional (LR), or metastatic (M) recurrence. Main disease characteristics and RT fields were examined in relation to sites of recurrence. RESULTS: One hundred forty-one patients were identified with 244 sites of failure on imaging. Of these, 108 patients had received RT to the PB alone and 33 RT to the PB and pelvic lymph nodes (PB+PLN). Androgen-deprivation therapy was used concomitantly in 50 patients (35%). The median PSA at imaging was 1.6 ng/ml (range, 0-86.7). In all, 74 patients (52%) had M disease (44% in the PB group and 79% in the PB+PLN group), 61 (43%) had LR failure (52% in the PB alone group and 15% in the PB+PLN group), and six (4%) had L-only failure, at a median of 26.7 months (range, 5-110.3) from RT. Metastases were in extra-pelvic LN (37 (15%)), bones (66 (27%)), and visceral organs (eight (3%)). Fifty-three (48%) of the pelvic LN failures in the PB group would have been encompassed by standard PLN RT volume. CONCLUSION: We found that most patients evaluated for BF after postoperative RT recurred outside the RT field. Isolated pelvic nodal failure was rare in those receiving RT to the PB+PLN but accounted for half of failures in those receiving PB alone RT. Imaging directed salvage treatment could be helpful to personalize radiation therapy plan.

Primary site disease and recurrence location in ovarian cancer patients undergoing primary debulking surgery vs. interval debulking surgery.

INTRODUCTION: The natural history and patterns of ovarian cancer (OC) relapse are still unclear. Recurrent disease can be peritoneal, parenchymal, or nodal. This study aims to analyze the location and pattern of OC recurrence according to the primary site of disease and to the type of surgical approach used. MATERIAL AND METHODS: All OC patients underwent primary debulking surgery (PDS) or interval debulking surgery (IDS), with 2014 FIGO stage III-IV, and with platinum-sensitive recurrence were included in the study. Primary disease location and site of recurrences were divided into peritoneal, parenchymal, and nodal, according to the presence of peritoneal carcinomatosis, parenchymal metastasis, and nodal involvement, respectively. RESULTS: A total of 355 patients were initially considered; of them, 295 met the inclusion criteria. Two hundred thirty-three patients obtained no macroscopic residual tumor at the end of primary surgical treatment. Primary parenchymal disease relapsed in 84.6% cases at a parenchymal site (p < 0.001), 97.2% of peritoneal diseases relapsed on the peritoneum (p < 0.001), and 100% of nodal diseases had a nodal recurrence (p < 0.001). Stratifying by the surgical approach all these correlations have been confirmed both in the PDS (p < 0.001) and IDS (p < 0.001) groups. CONCLUSION: Our study shows that the site of relapse in cases of platinum-sensitive OC recurrence is closely related to the primary location of the disease, regardless of the type of initial treatment. Therefore, more attention during followup should be paid to areas where the initial tumor was present.

Pattern of recurrence in patients with endometrial cancer: A retrospective study.

INTRODUCTION: Endometrial cancer (EC) known prognostic factors are not sufficient to predict either outcome or recurrence rate/site: to investigate EC recurrence patterns according to ESMO-ESGO-ESTRO risk classes, could be beneficial for a more tailored adjuvant treatment and follow-up schedule. METHODS: 758 women diagnosed with EC, and a 5-years follow-up, were enrolled: they were divided into the ESMO-ESGO-ESTRO risk classes (low LR, intermediate IR, intermediate-high I-HR, and highrisk HR) and surgically treated as recommended, followed by adjuvants therapies when appropriate. RESULTS: Higher recurrence rate (RR) was significantly detected (p < 0,001) in the HR group (40,3%) compared to LR (9,6%), IR (16,7%) and I-HR (17,1%). Recurrences were detected more frequently at distant sites (64%) compared to pelvic (25,3%) and lymph nodes (10,7%) recurrences (p < 0,0001): only in LR group, no differences were detected between local and distant recurrences. 5-Year distant-free (LR 99%, IR 94%,I-HR 86%, HR 88%) and local-free survivals (LR 99%, IR 100%,I-HR 98%, HR 95%) significantly differ between groups (p < 0,0001 and p = 0,003, respectively). Adjuvant therapy modifies RRs only in LR group (p = 0,01). CONCLUSION: To identify biological factors to stratify patients at higher risk of relapse is needed. Distant site relapse could be the main reason of endometrial cancer failure follow-up, independently or in addition to their risk class prognosis.

Treatment outcomes and incidence of brain metastases in pulmonary large cell neuroendocrine carcinoma.

INTRODUCTION: Large cell neuroendocrine carcinoma (LCNEC) is a rare type of high-grade pulmonary neuroendocrine tumor. The study objective is to investigate its survival outcomes, incidence of brain metastases, and patterns of recurrence. METHODS: This is a single center study of patients with pathologic diagnosis of pulmonary LCNEC. Patient data were collected retrospectively and analyzed, including survival, incidence of brain metastases, and patterns of recurrence. RESULTS: Of 87 patients (stages I: 24, II: 14, III: 23, IV: 26), 52 were managed curatively and 35 palliatively. The median follow-up time was 17.3 months (range 0.6-89.5) for those treated with curative intent and 7.0 months (range 0.1-28.6) for those treated palliatively. The 2- and 5-year overall survival (OS) rates are 48.4% and 25.5% for the curative group, with a median OS of 13.5 months. In the palliative group, the OS are 30.8% at 1 year and 6.8% at 2 years, with a median OS of 7.0 months. Thirty-eight of 52 (73%) patients treated with curative intent had disease relapse, with the common sites being regional lymph nodes (20), brain (18), bones (11), and liver (9). The incidence of brain recurrence among those managed curatively are 21.4% and 41.3%, respectively at 1 and 2 years. Of 18 patients experiencing brain metastases, 14 developed them as part of a first relapse. CONCLUSIONS: LCNEC's survival outcomes are poor. The incidence of brain metastases is higher than what is observed for other types of nonsmall cell lung cancers. Prophylactic cranial irradiation should be investigated as a means of improving outcomes.

Neoadjuvant Platinum-based Chemotherapy Followed by Radical Hysterectomy for Stage Ib2-IIb Adenocarcinoma of the Uterine Cervix - An Italian Multicenter Retrospective Study.

AIM: To assess the patterns of recurrence and clinical outcomes of patients with cervical adenocarcinoma who underwent neoadjuvant platinum-based chemotherapy (NACT) followed by radical hysterectomy. PATIENTS AND METHODS: Data were retrospectively analyzed for 82 patients with International Federation of Gynecology and Obstetrics stage Ib2-IIb cervical adenocarcinoma who underwent this chemo-surgical treatment. The median follow-up of survivors was 89 months (range=5-208 months). RESULTS: Pathological complete response, optimal response and suboptimal response with intra-cervical residual disease were obtained in five (6%), 10 (12%) and 36 (44%) patients, respectively. Adjuvant external-beam radiotherapy with or without concurrent chemotherapy was administered to 47 patients. Nineteen (23%) out of the 82 patients experienced recurrence after a median of 12 months (range=5.3-86.8 months). Recurrent disease was pelvic in 12 (63%) patients, extra-pelvic in five (26%), and both pelvic and extra-pelvic in two (10%). According to pathological response, tumor relapsed in 10% of optimal responders, 14% of sub-optimal responders with intra-cervical residual disease, and 36% of sub-optimal responders with extra-cervical residual disease or non-responders. Five-year recurrence-free and overall survival were 77% and 84%, respectively. Patients who achieved an optimal response or sub-optimal response with intra-cervical residual disease had better 5-year recurrence-free (87% vs. 64%, p=0.017) and overall (92% vs. 74%, p=0.012) survival than those who had sub-optimal response with extra-cervical residual disease or no response. The latter had a 1.441-fold higher risk of recurrence and a 1.652-fold higher risk of death than those who obtained an optimal response or a sub-optimal response with intra-cervical residual disease. CONCLUSION: NACT followed by radical hysterectomy may be an option for patients with stage Ib2-IIb adenocarcinoma of the uterine cervix.

Epidermal Growth Factor Receptor Expression Predicts Time and Patterns of Recurrence in Patients with Glioblastoma After Radiotherapy and Temozolomide.

BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the potential role of epidermal growth factor receptor (EGFR) protein expression in predicting the modality of treatment failure in glioblastoma (GB). METHODS: Patients with unifocal GB undergoing surgery and postoperative radiochemotherapy from February 2008 to July 2015 were included into the study. The EGFR protein expression level was assessed by immunohistochemistry in GB tissues and classified into high and low expression. Time to progression (TTP) and pattern of recurrence (PR) were evaluated. PRs were classified as central, in-field, marginal, or distant recurrences. RESULTS: After a median follow-up time of 13 months (range, 6-67 months), 102 patients (79.1%) showed recurrences that were detectable on magnetic resonance imaging. Median TTP was 9 months after the completion of radiochemotherapy. EGFR expression was significantly correlated with TTP (log-rank test, P = 0.003) and PR (Fisher exact test, P = 0.01). The low-EGFR group had a median TTP of 13 months and a prevalence of central/in-field recurrences (accounting to a total 81%). The high-EGFR group had a shorter median TTP (6 months) and a higher rate of marginal/distant recurrences (55.6%). CONCLUSIONS: Different modality of recurrence related to EGFR expression in patients with GB envisages implication for target contouring of radiotherapy volumes and other therapeutic strategies.

Re-irradiation after gross total resection of recurrent glioblastoma : Spatial pattern of recurrence and a review of the literature as a basis for target volume definition.

BACKGROUND: Currently, patients with gross total resection (GTR) of recurrent glioblastoma (rGBM) undergo adjuvant chemotherapy or are followed up until progression. Re-irradiation, as one of the most effective treatments in macroscopic rGBM, is withheld in this situation, as uncertainties about the pattern of re-recurrence, the target volume, and also the efficacy of early re-irradiation after GTR exist. METHODS: Imaging and clinical data from 26 consecutive patients with GTR of rGBM were analyzed. The spatial pattern of recurrences was analyzed according to the RANO-HGG criteria ("response assessment in neuro-oncology criteria for high-grade gliomas"). Progression-free (PFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. Furthermore, a systematic review was performed in PubMed. RESULTS: All but 4 patients underwent adjuvant chemotherapy after GTR. Progression was diagnosed in 20 of 26 patients and 70% of recurrent tumors occurred adjacent to the resection cavity. The median extension beyond the edge of the resection cavity was 20 mm. Median PFS was 6 months; OS was 12.8 months. We propose a target volume containing the resection cavity and every contrast enhancing lesion as the gross tumor volume (GTV), a spherical margin of 5-10 mm to generate the clinical target volume (CTV), and a margin of 1-3 mm to generate the planning target volume (PTV). Re-irradiation of this volume is deemed to be safe and likely to prolong PFS. CONCLUSION: Re-irradiation is worth considering also after GTR, as the volumes that need to be treated are limited and re-irradiation has already proven to be a safe treatment option in general. The strategy of early re-irradiation is currently being tested within the GlioCave/NOA 17/Aro 2016/03 trial.

Protocol of the PANCALYZE trial: a multicenter, prospective study investigating the tumor biomarkers CXCR4, SMAD4, SOX9 and IFIT3 in patients with resected pancreatic adenocarcinoma to predict the pattern of recurrence of the disease.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies today with an urgent need for novel therapeutic strategies. Biomarker analysis helps to better understand tumor biology and might emerge as a tool to develop personalized therapies. The aim of the study is to investigate four promising biomarkers to predict the clinical course and particularly the pattern of tumor recurrence after surgical resection. DESIGN: Patients undergoing surgery for PDAC can be enrolled into the PANCALYZE trial. Biomarker expression of CXCR4, SMAD4, SOX9 and IFIT3 will be prospectively assessed by immunohistochemistry and verified by rt.-PCR from tumor and adjacent healthy pancreatic tissue of surgical specimen. Immunohistochemistry expression pattern of all four biomarkers will be combined into a single score. Beginning with the hospital stay clinical data from enrolled patients will be collected and followed. Different adjuvant chemotherapy protocols will be used to create subgroups. The combined biomarker expression score will be correlated with the further clinical course of the patients to test the hypothesis if CXCR4 positive, SMAD4 negative, SOX9 positive, IFIT3 positive tumors will predominantly develop metastatic spread. DISCUSSION: Pancreatic cancer is associated with different patterns of progression requiring personalized therapeutic strategies. Biomarker expression analysis might be a tool to predict the pattern of tumor recurrence and discriminate patients that develop systemic metastatic disease from those with tumors that rather develop local recurrence over time. This data might lead to personalized adjuvant treatment decisions as patients with tumors that stay localized might benefit from adjuvant local therapies like radiochemotherapy as compared to those with systemic recurrence who would benefit exclusively from chemotherapy. Moreover, the pattern of propagation might be a predefined characteristic of pancreatic cancer determined by the genetic signature of the tumor. In the future, biomarker expression analysis could be performed on tumor biopsies to develop personalized therapeutic pathways right after diagnosis of cancer. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00006179 .

Patterns of recurrence and outcomes in surgically treated women with endometrial cancer according to ESMO-ESGO-ESTRO Consensus Conference risk groups: Results from the FRANCOGYN study Group.

OBJECTIVES: The purpose of this study was to analyse the endometrial cancer (EC) patterns of recurrence based on a large French multicentre database according to ESMO-ESGO-ESTRO classification. METHODS: Data of women with histologically proven EC who received primary surgical treatment between January 2001 and December 2012 were retrospectively abstracted from seven institutions with prospectively maintained databases. The endpoints were recurrence, recurrence free survival (RFS) and overall survival (OS). Time to the first EC recurrence in a specific site was evaluated by using cumulative incidence analysis (Gray's test). RESULTS: Data from 829 women were analysed in whom recurrences were observed in 176 (21%) with a median and mean time to recurrence of 13 and 19.5months, respectively. High (35%) and high-intermediate risk groups (16%) were associated with higher recurrence rates compared with low (9%) and intermediate (9%) risk patients (p<0.0001). Women with high risk EC had a higher 5-year cumulative incidence of distant recurrence (20.7%) than women with high-intermediate, intermediate and low risk EC (5.6%, 3.5%, 3.3%), (p<0.001), respectively. Women with high risk and high-intermediate risk EC had a higher 5-year cumulative incidence of loco-regional recurrence (24.3% and 16.6%, respectively) than women with intermediate and low risk EC (6.6% and 6.5%, respectively), (p<0.001). CONCLUSIONS: We report specific time and site patterns of first recurrence according to the ESMO/ESGO/ESTRO classification. Sites and hazard rates for recurrence differ widely between subgroups over time. Defining patterns of EC recurrence may provide useful information for developing follow-up recommendations and designing therapeutic approaches.

Pattern of recurrence and factors associated with cerebrospinal fluid dissemination of glioblastoma in Chinese patients.

BACKGROUND: Pattern of recurrence of glioblastoma (GBM) seems to have undergone some shifts from distant metastasis as a rarity to a higher proportion, including disease disseminated via cerebrospinal fluid (CSF) pathway. There is still no report on the pattern of recurrence for Chinese population. Here, we evaluated the pattern of recurrence of GBM in Chinese patients along with factors that could affect the distribution of recurrence. METHODS: Medical records of GBM patients with definite recurrence were reviewed. Local recurrence was defined as tumor regrowth within the preoperative abnormal signals on magnetic resonance imaging (MRI) T2 sequence. New recurrence was a new lesion away from the preoperative T2 abnormalities. New recurrence in contact with CSF pathways was registered as new CSF dissemination. Progress-free survival (PFS) and survival after progress were compared using the Kaplan-Meier survival curves. Potential risk factors for new CSF dissemination were assessed using univariate models followed by multivariate analysis. RESULTS: Thirty-six patients were proven to have recurrence; 22 local and 14 new recurrences. Among the 14 patients, 11 had new CSF dissemination. Median PFS for local, new parenchymal recurrence, and new CSF dissemination were 5.5 months, 9.9 months, and 12.1 months, whereas survival after progress were 6.1 months, 5.7 months, and 16.9 months, respectively. The ventricular entry during surgery and the completion of concomitant chemoradiotherapy were risk factors for new CSF dissemination. O6-methylguanine-DNA methyltransferase methylation was associated with the development of CSF dissemination. CONCLUSION: The majority of recurrence remained local (22/36, 61%). However, CSF dissemination was up to 30% (11/36). PFS for patients with CSF dissemination was the longest, and paradoxically survival after progress was the shortest. Ventricular entry should be avoided. Whole craniospinal MRI surveillance should be included for these patients.

Risk factors related to late metastases in 1,372 melanoma patients disease free more than 10 years.

In many centers, Stage I-II melanoma patients are considered "cured" after 10 years of disease-free survival and follow-up visits are interrupted. However, melanoma may relapse also later. We retrospectively analyzed a cohort of 1,372 Stage I-II melanoma patients who were disease-free 10 years after diagnosis. The aim of this study was to characterize patients who experienced a late recurrence and to compare them to those who remained disease-free to identify possible predictive factors. Multivariate Cox proportional-hazards regression analyses were carried out to evaluate the influence of different factors on the risk of recurrence. Seventy-seven patients out of 1,372 (5.6%) relapsed, 52 in regional sites and 25 in distant ones. The majority of patients (31 out of 52) experienced late recurrence in regional lymph nodes. Brain and lung were the most common site of single distant recurrence (24% each). Patients with multiple distant metastases showed a brain and lung involvement in, respectively, 40 and 48% of cases. A Cox proportional-hazards regression model analysis showed the independent role of age under 40 years, Breslow thickness >2 mm, and Clark Level IV/V in increasing the risk of Late Recurrence. These patients should be followed-up for longer than 10 years. The pattern of recurrence suggests that melanoma cells can be dormant preferentially in lymph nodes, brain and lung. A particular attention should be reserved to these anatomic sites during the follow-up after 10 years of disease-free.

Recurrence pattern after conservative surgery for papillary thyroid carcinoma.

OBJECTIVE: Risk-based treatment represents the optimal management strategy for papillary thyroid carcinoma; however, the optimal extent of thyroidectomy and neck dissection remains controversial. This study aims to clarify the pattern of recurrence after conservative surgery in patients with papillary thyroid carcinoma. METHODS: We retrospectively reviewed 93 patients with papillary thyroid carcinoma treated with conservative surgery. We analyzed recurrence rate, recurrence pattern, risk factors for recurrence, salvage treatment, and disease-free survival (DFS) in patients stratified according to risk. RESULTS: The recurrence rate was significantly lower in the low-risk group compared with the high-risk group (14% vs 34%; p<0.01). The recurrence pattern also differed between the two groups, with ipsilateral lateral neck recurrence being more common in the low-risk group (9%), while contralateral lateral neck recurrence was more common in the high-risk group (18%). Patients with contralateral thyroid lobe metastasis and/or direct contralateral thyroid lobe invasion showed a significantly higher rate of contralateral lateral neck metastasis than patients negative for both these features. The overall 5-year DFS was 81% in all patients. Advanced T and N classification, large primary tumor (≥4cm), extrathyroidal invasion, and high-risk group were significantly associated with poorer 5-year DFS in univariate analysis. CONCLUSION: Conservative surgery may represent a good treatment option for patients with low-risk papillary thyroid carcinoma. Tumor recurrence patterns differ between risk groups, with contralateral thyroid lobe lesions and direct contralateral lobe invasion being risk factors for contralateral lateral neck recurrence.

Patterns of local recurrence in rectal cancer after a multidisciplinary approach.

Improvements in surgery and the application of combined approaches to fight rectal cancer have succeeded in reducing the local recurrence (LR) rate and when there is LR it tends to appear later and less often in isolation. Moreover, a subtle change in the distribution of LRs with respect to the pelvis has been observed. In general terms, prior to total mesorectal excision the most common LRs were central types (perianastomotic and anterior) while lateral and posterior forms (presacral) have become more common since the growth in the use of combined treatments. No differences have been reported in the current pattern of LRs as a function of the type of approach used, that is, neo-adjuvant therapies (short-term or long-course radiotherapy, or chemoradiotherapy versus extended lymphadenectomy, though there is a trend towards posterior or presacral LR in patients in the Western world and lateral LR in Asia. Nevertheless, both may arise from the same mechanism. Moreover, as well as the mode of treatment, the type of LR is related to the height of the initial tumor. Nowadays most LRs are related to the advanced nature of the disease. Involvement of the circumferential radial margin and spillage of residual tumor cells from lymphatic leakage in the pelvic side wall are two plausible mechanisms for the genesis of LR. The patterns of pelvic recurrence itself (pelvic subsites) also have important implications for prognosis and are related to the potential success of salvage curative approach. The re-operability for cure and prognosis are generally better for anastomotic and anterior types than for presacral and lateral recurrences. Overall survival after LR diagnosis is lower with radio or chemoradiotherapy plus optimal surgery approaches, compared to optimal surgery alone.