Extensive Tumor Load Research Articles

Advanced Automated Model for Robust Bone Marrow Segmentation in Whole-body MRI.

To establish an advanced automated bone marrow (BM) segmentation model on whole-body (WB-)MRI in monoclonal plasma cell disorders (MPCD), and to demonstrate its robust performance on multicenter datasets with severe myeloma-related pathologies. The study cohort comprised multi-vendor, multi-protocol imaging data acquired with varying field strength across 8 different centers. In total, 210 WB-MRIs of 207 MPCD patients were included. An nnU-Net algorithm was established for segmenting the individual bone marrow spaces (BMS) of the spine, pelvis, humeri and femora (advanced segmentation model). For this task, 186 T1-weighted (T1w) WB-MRIs from center 1 were used in the training set. Test sets included 12 T1w WB-MRIs from center 2 (I) and 9 T1w WB-MRIs from centers 3-8 (II). Example cases were included to showcase segmentation performance on T1w WB-MRIs with extensive tumor load. The segmentation accuracy of the advanced segmentation model was compared to a prior established basic segmentation model by calculating Dice scores and using the Wilcoxon signed-rank test. The mean Dice score on the individual BMS was 0.89±0.13 (test set I) and 0.88±0.11 (test set II), significantly higher than the Dice scores of a prior basic model (p<0.05). Dice scores for the BMS of the individual bones ranged from 0.77 to 0.96 (test set I), and 0.81 to 0.95 (test set II). BM altered by myeloma-relevant pathologies, artifacts or low imaging quality was precisely segmented. The advanced model performed reliable, automated segmentations, even on heterogeneously acquired multicenter WB-MRIs with severe pathologies.

Nationwide clinical practice variation for reconstructive surgery following oral cavity cancer from the Dutch Head and Neck Audit: Are we all doing the same?

IntroductionQuality registries provide real-world data that can drive quality improvement which often starts with reducing interhospital variation. We explored outcomes and the extent of nationwide interhospital variation for patients undergoing reconstructive surgery after oral cavity cancer (OCC) using the Dutch Head and Neck Audit (DHNA). Material and MethodsWithin the DHNA, we selected all OCC patients between 2018 and 2022 who underwent curative reconstructive surgery. Patient, tumour, and treatment characteristics were compared, including reconstruction strategies (skin grafting, local transposition, pedicled and free flaps). Of those treated with free flap reconstruction, postoperative complications were scored according to the Clavien-Dindo (CD) classification and labelled minor (CD 1-2) or major (CD ≥3). ResultsA total of 1,383 patients were included in the analysis. Especially for patients with stage I tumours (10%), a wide variation in reconstructive surgeries was observed between centres, with a preference for local transposition (42.6%). Free flaps were used most for patients with a more extensive tumour load (65.4% - 89.2%), with the radial forearm flap as the preferred technique (54.7%, range 33.7% - 80.8%). Thirty-four percent of patients treated with a free flap had postoperative complications, with 38 cases of total flap loss (overall 3.9% complications). ConclusionStrategies and percentages varied strongly across centres, showing high interhospital variation in applied techniques and outcomes, and the need for national data improvement.

Differential role of residual metabolic tumor volume in inoperable stage III NSCLC after chemoradiotherapy\u2009\xb1\u2009immune checkpoint inhibition

BackgroundThe PET-derived metabolic tumor volume (MTV) is an independent prognosticator in non-small cell lung cancer (NSCLC) patients. We analyzed the prognostic value of residual MTV (rMTV) after completion of chemoradiotherapy (CRT) in inoperable stage III NSCLC patients with and without immune checkpoint inhibition (ICI).MethodsFifty-six inoperable stage III NSCLC patients (16 female, median 65.0 years) underwent 18F-FDG PET/CT after completion of standard CRT. rMTV was delineated on 18F-FDG PET/CT using a standard threshold (liver SUVmean + 2 × standard deviation). 21/56 patients underwent additional ICI (CRT-IO, 21/56 patients) thereafter. Patients were divided in volumetric subgroups using median split dichotomization (MTV ≤ 4.3 ml vs. > 4.3 ml). rMTV, clinical features, and ICI-application were correlated with clinical outcome parameters (progression-free survival (PFS), local PFS (LPFS), and overall survival (OS).ResultsOverall, median follow-up was 52.0 months. Smaller rMTV was associated with longer median PFS (29.3 vs. 10.5 months, p = 0.015), LPFS (49.9 vs. 13.5 months, p = 0.001), and OS (63.0 vs. 23.0 months, p = 0.003). CRT-IO patients compared to CRT patients showed significantly longer median PFS (29.3 vs. 11.2 months, p = 0.034), LPFS (median not reached vs. 14.0 months, p = 0.016), and OS (median not reached vs. 25.2 months, p = 0.007). In the CRT subgroup, smaller rMTV was associated with longer median PFS (33.5 vs. 8.6 months, p = 0.001), LPFS (49.9 vs. 10.1 months, p = 0.001), and OS (63.0 vs. 16.3 months, p = 0.004). In the CRT-IO subgroup, neither PFS, LPFS, nor OS were associated with MTV (p > 0.05 each). The findings were confirmed in subsequent multivariate analyses.ConclusionIn stage III NSCLC, smaller rMTV is highly associated with superior clinical outcome, especially in patients undergoing CRT without ICI. Patients with CRT-IO show significantly improved outcome compared to CRT patients. Of note, clinical outcome in CRT-IO patients is independent of residual MTV. Hence, even patients with large rMTV might profit from ICI despite extensive tumor load.

Prostate volume index and prostatic chronic inflammation predicted low tumor load in 945 patients at baseline prostate biopsy.

To assess associations of prostate volume index (PVI), defined as the ratio of the volume of the central transition zone to the volume of the peripheral zone of the prostate and prostatic chronic inflammation (PCI) as predictors of tumor load by number of positive cores (PC) in patients undergoing baseline random biopsies. Parameters evaluated included age, PSA, total prostate volume, PSA density, digital rectal exam, PVI, and PCI. All patients underwent standard transperineal random biopsies. Tumor load was evaluated as absent (no PC), limited (1-3 PC), and extensive (more than 3 PC). The association of factors with the risk of tumor load was evaluated by the multinomial logistic regression model. The study evaluated 945 patients. Cancer PC were detected in 477 (507%) cases of whom 207 (43.4%) had limited tumor load and 270 (56.6%) had extensive tumor load. Among other factors, comparing patients with limited tumor load with negative cases, PVI [odds ratio, OR = 0.521, 95% confidence interval (CI) 0.330-0.824; p < 0.005] and PCI (OR = 0.289, 95% CI 0.180-0.466; p < 0.0001) were inversely associated with the PCA risk. Comparing patients with extensive tumor load with negative patients, PVI (OR = 0.579, 95% CI 0.356-0.944; p = 0.028), and PCI (OR = 0.150, 95% CI 0.085-0.265; p < 0.0001), predicted PCA risk. Comparing extensive tumor load with limited tumor load patients, PVI and PCI did not show any association with the tumor load. Increased PVI and the presence of PCI decreased the risk of increased tumor load and associated with less aggressive prostate cancer biology in patients at baseline random biopsies.

Impact of Surgical Treatment for Recurrence After 2-Stage Hepatectomy for Colorectal Liver Metastases, on Patient Outcome.

To evaluate the impact of repeat surgery for recurrence on the long-term survival after 2-stage hepatectomy (TSH) for extensive colorectal liver metastases (CRLM). Although TSH is now deemed effective for selected patients with extensive bilobar CRLM, disease recurrence after TSH is very frequent because of the extensive tumor load. Among a total cohort of 1235 patients who underwent hepatectomy for CRLM between 1992 and 2012, 139 with extensive bilobar CRLM were scheduled for TSH. Of these, 93 patients had completion of TSH and were enrolled in this study. The 5-year overall survival (OS) rate after TSH was 41.3%. Twenty-two patients (23.7%) had a concomitant extrahepatic disease (EHD), and curative resection of concomitant EHD was achieved in 13 patients. Among the 81 patients who achieved complete tumor removal for primary, CRLM, and concomitant EHD, 62 (76.5%) had recurrence. Repeat surgery was performed in 38 patients; 35 for recurrence after curative surgery and 3 for liver recurrence with unresected concomitant EHD or primary tumor. Of these 38 patients, 31 were salvaged. The patients who underwent repeat surgery had a significantly longer OS than those who did not (45.8% vs 26.3%; P = 0.0041). A multivariate analysis revealed that repeat surgery was an independent prognostic factor of the OS after TSH (hazard ratio 0.31, P = 0.0012). Repeat surgery for recurrence after TSH may be crucial for the long-term survival in patients with extensive bilobar CRLM. Intensive oncosurgical surveillance is essential to avoid missing the chance for repeat surgery after TSH.

Prostate volume index and prostatic chronic inflammation have an effect on tumor load at baseline random biopsies in patients with normal DRE and PSA values less than 10 ng/ml: results of 564 consecutive cases.

Background:To assess the association of prostate volume index (PVI), defined as the ratio of the central transition zone volume (CTZV) to the peripheral zone volume (PZV), and prostatic chronic inflammation (PCI) as predictors of prostate cancer (PCA) load in patients presenting with normal digital rectal exam (DRE) and prostate-specific antigen (PSA) ⩽ 10 ng/ml at baseline random biopsies.Methods:Parameters evaluated included age, PSA, total prostate volume (TPV), PSA density (PSAD), PVI and PCI. All patients underwent 14 core transperineal randomized biopsies. We considered small and high PCA load patients with no more than three (limited tumor load) and greater than three (extensive tumor load) positive biopsy cores, respectively. The association of factors with the risk of PCA was evaluated by logistic regression analysis, utilizing different multivariate models.Results:564 Caucasian patients were included. PCA and PCI were detected in 242 (42.9%) and 129 (22.9%) cases, respectively. On multivariate analysis, PVI and PCI were independent predictors of the risk of detecting limited or extensive tumor load. The risk of detecting extensive tumor load at baseline biopsies was increased by PSAD above the median and third quartile as well as PVI ⩽ 1 [odds ratio (OR)=1.971] but decreased by PCI (OR=0.185; 95% CI: 0.088–0.388).Conclusions:Higher PVI and the presence of PCI predicted decreased PCA risk in patients presenting with normal DRE, and a PSA ⩽ 10 ng/ml at baseline random biopsy. In this subset of patients, a PVI ⩽ or >1 is able to differentiate patients with PCA or PCI.

Chemotherapy in NETs: When and how.

The majority of neuroendocrine tumours (NETs) are well-differentiated tumours that follow an indolent course, in contrast to a minority of poorly differentiated neuroendocrine carcinomas (NECs) which exhibit an aggressive course and assocaited with an overall short survival. Although surgery is the only curative treatment for NETs it is not always feasible,necessitating the application of other therapies including chemotherapy. Streptozotocin (STZ)-based regimens have long been used for advanced or metastatic well-to-moderately differentiated (G1-G2) NETs, especially those originating from the pancreas (pNETs). In poorly differentiated grade 3 (G3) tumours, platinum-based chemotherapy is recommended as first-line therapy, albeit without durable responses. Although data for temozolomide (TMZ)-based chemotherapy are still evolving, this treatment may replace STZ-based regimens in pNETs due to its better tolerability and side effect profile. In addition, there is evidence that TMZ could also be used in the subgroup of well-differentiated G3 NETs. There is less clear-cut evidence of a benefit for chemotherapy in intestinal NETs, but still evolving data suggest that TMZ may be efficacious in particular patients. In lung and thymic carcinoids, chemotherapy is reserved for patients with progressive metastatic disease in whom other treatment options are unavailable. Overall, chemotherapy is indicated in patients who have progressed on first-line treatment with somatostatin analogues, have extensive tumour load or exhibit rapid growth following a period of follow-up, and/or have a high proliferative rate; it may occasionally can be used in a neo-adjuvant setting. Prospective randomised studies are awaited to substantiate the role of chemotherapy in the therapeutic algorithm of NETs along with other evolving treatments.

Is Liver Transplantation an Option in Colorectal Cancer Patients with Nonresectable Liver Metastases and Progression on All Lines of Standard Chemotherapy?

About 50 % of patients with metastatic colorectal cancer (CRC) will develop metastatic disease with liver as primary metastatic site. The majority of CRC patients has nonresectable disease and receives palliative chemotherapy. Overall survival (OS) from time of progression on last line of chemotherapy in metastatic CRC is about 5 months. CLM have been considered a contraindication for liver transplantation. However, we have previously reported 5-year OS of 60 % after liver transplantation for nonresectable CLM. There were six patients who had progressive disease (PD) on last line of standard chemotherapy at the time of liver transplantation; here we report the outcome for these six patients. Patients with nonresectable liver-only CLM received liver transplantation in the SECA study, a subgroup of six patients whose disease had progressed on all standard lines of chemotherapy. These patients with nonresectable disease and PD on the last line of standard chemotherapy at time of liver transplantation had 8-35 metastatic lesions in the liver with the largest diameter at 2.8-13.0 cm. All patients had a relapse within 2.1-12.4 months after liver transplantation. Some patients received treatment with curative intent at the time of relapse, and median OS after transplantation was 41 months with a Kaplan-Meier calculated 5-year OS of 44 %. Liver transplantation in nonresectable CLM patients with extensive tumor load and PD on the last line of chemotherapy had extended OS compared with any other treatment option reported in the literature.

Comparison of 18F-FDG PET/CT and 68Ga-DOTATATE PET/CT Imaging in Metastasized Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is a rare but very aggressive neuroendocrine tumor of the skin in elderly patients with higher mortality compared with melanoma. No evidence-based standardized chemotherapy exists for metastasized patients.We report the case of an 87-year-old patient with the history of resection of a large MCC of the parietal scalp planned for radiotherapy and staged with FDG PET/CT showing disseminated distant metastases. Ga-DOTATATE PET/CT revealed more extensive tumor load compared with FDG, and due to the intensive expression of somatostatin receptors the patient qualified for Y DOTATOC therapy.

Timing of debulking surgery in advanced ovarian cancer

It is clear that primary debulking remains the standard of care within the treatment of advanced ovarian cancer (FIGO stage III and IV). This debulking surgery should be performed by a gynecological oncologist without any residual tumor load, or so-called "optimal debulking." Over the last decades, interest in the use of neoadjuvant chemotherapy together with an interval debulking has increased. Neoadjuvant therapy can be used for patients who are primarily suboptimally debulked due to an extensive tumor load. In this situation, based on the randomized European Organization for Research and Treatment of Cancer-Gynaecological Cancer Group trial, interval debulking by an experienced surgeon improves survival in some patients who did not undergo optimal primary debulking surgery. Based on the GOG 152 data, interval debulking surgery does not seem to be indicated in patients who underwent primarily a maximal surgical effort by a gynecological oncologist. Neoadjuvant chemotherapy can also be used as an alternative to primary debulking. In retrospective analyses, neoadjuvant chemotherapy followed by interval debulking surgery does not seem to worsen prognosis compared to primary debulking surgery followed by chemotherapy. However, we will have to wait for the results of future randomized trials to know whether neoadjuvant chemotherapy followed by interval debulking surgery is a good alternative to primary debulking surgery in stage IIIc and IV patients. Open laparoscopy is probably the most valuable tool for evaluating the operability primarily or at the time of interval debulking surgery.

Validation of FDG positron emission tomography for differentiation of unknown pulmonary lesions.

The impact of the (2-(fluorine-18)-fluoro-2-2deoxy-D-glucose)-positron emission tomography ((18)F-FDG-PET) for discrimination of pulmonary lesions was evaluated in a single centre prospective study. In the study, 109 patients with pulmonary lesions of unknown origin verified by computed tomography were enrolled consecutively (April 1999--May 2000). They were subject to (18)F-FDG-PET diagnostics. (18)F-FDG-PET images were interpreted by two independent nuclear medicine physicians who were blinded to the results of other imaging procedures. In 87 patients, surgery was applied followed by histological investigation, which served as the gold standard. In 22 other patients, extensive tumour load or assumed benign dignity of the lesions prevented surgery. Overall sensitivity of (18)F-FDG-PET in 87 resected patients was 0.86. Differentiation in malignant (n = 69) and benign lesions (n = 18) revealed sensitivities of 0.9 and 0.72, respectively. Sensitivity of (18)F-FDG-PET in inflammatory lesions was markedly lower (0.43) than in benign tumours (0.91). Standard uptake values were significantly increased in malignant tumours compared with benign lesions (9.9 and 1.6, respectively; P = 0.035). There was a clear correlation of sensitivity with tumour size with a failure rate of 27% in lesions < or = 1cm (n = 15), 10% (n = 20) in lesions between 1 and 2 cm and 12% (n = 45) above 2 cm. In primary bronchial carcinoma, a clear correlation of sensitivity was observed with regard to tumour grading (G1, three out of five; G2, 24 out of 27; G3, 26 out of 26; and G4, one out of one). Lymph node involvement was correctly suggested in 10 out of 19 (52.6%) patients. However, false positive lymph node enhancement was indicated in one out of 18 (5.5%) operated patients with benign lesions and eight out of 39 (20.5%) with bronchial carcinoma. (18)F-FDG-PET at present does not serve as the gold standard for early detection of small and well-differentiated tumours. However, it contributes efficiently to the detection of malignancy in tumours >1cm, which are moderately or poorly differentiated. Positive lymph node imaging must not preclude surgery but requires histological proof. Discrimination of benign and malignant pulmonary tumours by (18)F-FDG-PET appears to be hampered in inflammatory lesions.

Gastrostomy Using a “Gastrofix” as an Alternative for Nasogastric Tubes in Ovarian Cancer Surgery

Objective.The aim of this study was to evaluate the use of a gastrostomy instead of a nasogastric tube following surgery for advanced ovarian cancer.Design.This was a retrospective observational study.Setting.The study was performed in a university teaching hospital.Participants.Thirty-four women undergoing debulking surgery for ovarian carcinoma participated.Methods.In order to increase patients' comfort during the first postoperative days we inserted for gastric decompression a transcutaneous instead of a transnasal tube following debulking surgery. Only patients with bowel involvement and/or extensive tumor load in the upper abdomen were included in the study. In this study we report on the use of a gastrostomy using a Cystofix drainage catheter, resulting in what we call a “Gastrofix.” The Gastrofix was placed in 34 patients with ovarian cancer. In 32 (94%) patients an extraperitoneal hysterectomy and bilateral salpingo-oophorectomy was performed, in 16 (47%) a resection of the diaphragmatic peritoneum, in 14 (41%) patients a paraaortic lymphadenectomy, and in 12 (35%) patients part of the bowel was resected.Results.Free oral liquid intake and poor fiber diet were started after 5.5 days (median, range from 3–8 days) and 8 days (median, range from 4–12 days), respectively. The catheter was clamped off after 5 days (median, range from 2–8 days) and removed after 7 days (median, range from 3–11 days). Of the 34 patients only 12 (35%) received antiemetics (median of 4 days, range from 1–7 days). In 1 patient (3%) pain at the insertion site was observed on the third and fourth postoperative days. In 3 patients (9%) some fluid leakage at the insertion site was noted. In 4 patients (12%) the catheter fell out prematurely on days 0, 4, 6, and 9, respectively. In none of the patients were infection or fistulas at the insertion site noted. In all patients there was a satisfactory drainage of gastric content.Conclusion.After debulking surgery, the use of a Gastrofix resulted in an adequate gastrointestinal decompression without major complications. This technique may increase the comfort of the patient during the postoperative phase considerably.

Treatment of patients with metastatic pancreatic and gastrointestinal tumours with the somatostatin analogue Sandostatin: a phase II study including endocrine effects

Somatostatin analogues can suppress the secretion of some gastrointestinal hormones and growth factors involved in the growth regulation of gastrointestinal cancers and can inhibit the growth of experimental pancreatic tumours. Therefore, in a phase II study 34 patients with metastatic pancreatic (n = 14), colorectal (n = 16) and gastric cancer (n = 4) were treated with three daily subcutaneous injections of 100-200 micrograms of the somatostatin analogue Sandostatin (SMS 201-995). All patients had an extensive tumour load and 13 were pretreated with chemotherapy. Before Sandostatin treatment the patients with pancreatic cancer showed a higher mean plasma concentration of GH (P less than 0.05) and a lower concentration of 'total' somatomedin-C (P less than 0.005) compared with patients with colorectal cancer; there was no significant difference between these two groups in plasma levels of directly assayable somatomedin-C, EGF/TGF-alpha, insulin and prolactin. Within 3 days after start of treatment, somatomedin-C levels initially decreased (without a change in basal plasma GH levels), but returned to pretreatment levels within 4-13 weeks. Plasma insulin levels also were suppressed but only during the first 3-5 days of treatment. Plasma EGF-TGF-alpha levels increased significantly at day 5 of treatment only in the pancreatic cancer patients. Twenty-seven per cent of the patients showed stable disease for 3-9 months, but most patients experienced subjective improvement in the absence of serious side-effects. However, the overall survival remained disappointing, emphasising the need for better treatment regimens.

Combination chemotherapy in abdominal Burkitt's lymphoma.

In a clinical trial, 42 patients with abdominal Burkitt's lymphoma (BL) were treated with a combination regimen, code-named CVA, consisting of cyclophosphamide (CTX), vincristine, and cystosine arabinoside. In addition, intrathecal methotrexate (i.t. MTX) was administered as prophylaxis against subsequent central nervous system (CNS) involvement. Induced remissions, relapse, and survival were compared with those in a preceding group of 44 patients with abdominal BL treated with CTX along. Remission rate did not differ significantly in the two treatment groups, although induced remissions were higher in the CVA plus i.t. MTX-treated group (94% vs. 83%). Remission duration was significantly increases (p less than .05) and CNS relapse significantly reduced (p less than .05) in the group treated with CVA and i.t. MTX. The combination therapy was associated with higher early deaths during treatment, which adversely affected the overally survival. It is suggested that a reduction of the initial chemotherapeutic doses, particularly for patients with extensive tumor load, could further improve on the results of this trial.