Three-year Relapse-free Survival Rates Research Articles

Primary Mediastinal Germ Cell Tumors (PMGCT): A Real-world Analysis From A Tertiary Cancer Care Center in India

Background Primary mediastinal GCT (PMGCT) is a rare entity and comprises 10–15% of all mediastinal tumors. We present our institutional experience of MGCT treated with multimodality management. Materials and Methods We conducted a retrospective analysis between 2010 to 2020 of all mediastinal germ cell tumors registered at our center. Data on patient demographics, treatments received, treatment toxicities and response were recorded. Overall survival and relapse free survival were estimated using Kaplan–Meier methods. Results A total of 30 patients were identified. The median age was 25.5 (range, 18–45) years. Common presenting features included cough (70%) and shortness of breath (70%). Histology wise, 60% patients were non seminomatous histology, whereas 33.3% patients were Seminoma. Twenty-seven (90%) patients received chemotherapy as the first-line treatment, of whom five patients (16.6%) underwent surgery and radiation therapy subsequently. Median follow-up was 26.9 months. Thirteen patients (43.3%) had complete response (43.3%) and eight patients had partial response (26.7%), while three patients (5.5%) had progressive disease. Three-year relapse-free survival rate was 69.6% (95% confidence interval [CI], 42.8–85.6%). Overall survival (OS) at 3 years was 73.4% (95% CI, 49.4–87.3%). Patients with seminoma had a 3 year OS of 90.0% (95% CI, 47.3–98.5%) compared to those with non-seminoma (63.53% [95% CI, 32.3–83.3%]). Conclusions Multiagent chemotherapy is the backbone of treatment in PMGCT. Seminomatous PMGCT have excellent prognosis, while further improvement is needed in those with nonseminomatous tumor.

Safety and efficacy of prophylactic pegfilgrastim on day 3 of neoadjuvant DCF chemotherapy in elderly patients with resectable esophageal cancer.

375 Background: Neoadjuvant chemotherapy with docetaxel, cisplatin plus 5-FU (Neo DCF) is one of the standard treatment for resectable esophageal cancer (EC) based on the results of the JCOG1109 study, however, a high frequency (5-30%) of febrile neutropenia (FN) has been reported with NeoDCF and the elderly (patients) pts have higher risk for FN. A single arm phase II study indicated that use of primary prophylactic pegfilgrastim (PG) on day 3 of NeoDCF might prevent FN. We compared the frequency of neutropenia and FN with or without primary prophylactic administration of PG on day 3 of NeoDCF in elderly resectable EC pts. Methods: EC pts who had received NeoDCF between 2009 and 2022, were ≥70 years old, and had adequate organ functions and PS were selected for this retrospective study. Pts were divided into two groups with Day 3 PG-containing DCF (day3 prophylactic PG: D3PG) or No PG DCF (non-prophylactic PG: NPG). Three courses of DCF (DTX [day 1]: 70 mg/m2, CDDP [day 1]: 70 mg/m2, 5-FU [continuous infusion on days 1-5]: 750 mg/m2, every 3 weeks) were planned, and prophylactic antibiotics was administered on days 5-15 in each group if possible. We retrospectively evaluated the relative dose intensity (RDI), histopathological and clinical benefit, and adverse events. Results: A total of 67 pts (D3PG, 32; NPG, 35) with a median age of 73 years were identified. The PS (0/1/2) and clinical stage (I-II/III/ IVA-B [only supraclavicular lymph node]) were 18 (56.3%)/12 (37.5%)/2 (6.2%) and 1 (3.1%)/18 (56.3%)/13 (40.6%) in the D3PG group and 20 (57.1%)/15 (42.9%)/0 and 7 (20.0%)/24 (68.6%)/4 (11.4%) in the NPG group, respectively. Six pts in the D3PG group and 3 pts in the NPG group discontinued NeoDCF because of toxicity and progression. All pts except 1 in the D3PG group underwent surgery. The RDIs (DTX/CDDP/5-FU) were 0.90/0.83/0.90 in the D3PG group and 0.83/0.83/0.83 in the NPG group. Pts who achieved a pCR (D3PG/NPG) were 7/3 (22.6%/28.6%). The common grade ≥3 adverse events (D3PG/NPG) were neutropenia (12.5%/71.4%) and FN (6.3%/20.0%). Three-year relapse-free survival rate (D3PG/NPG) was 70.8%/54.4% (hazard ratio [HR] 0.525 [95% confidence interval (CI) 0.189-1.457], p=0.216). Three-year survival rate (D3PG/NPG) was 91.8%/70.5% (HR 0.497 [95%CI 0.104-2.35], p=0.378), respectively. Conclusions: The use of primary prophylactic PG on day 3 of preoperative DCF improved the safety and maintained the RDI in the D3PG group. The efficacy was comparable between the D3PG and NPG groups despite the higher number of pts with more advanced disease in the D3PG group.

Role of Preoperative Chemoradiotherapy in Clinical Stage II/III Rectal Cancer Patients Undergoing Total Mesorectal Excision: A Retrospective Propensity Score Analysis.

BackgroundAlthough the current standard preoperative chemoradiotherapy (PCRT) for stage II/III rectal cancer decreases the risk of local recurrence, it does not improve survival and increases the likelihood of preoperative overtreatment, especially in patients without circumferential resection margin (CRM) involvement.MethodsStage II/III rectal cancer without CRM involvement and lateral lymph node metastasis was radiologically defined by preoperative magnetic resonance imaging (MRI). Patients who received PCRT followed by total mesorectal excision (TME) (PCRT group) and upfront surgery (US) with TME (US group) between 2010 and 2016 were analyzed. We derived cohorts of PCRT group versus US group using propensity-score matching for stage, age, and distance from the anal verge. Three-year relapse-free survival rate, disease-free survival (DFS), and overall survival (OS) were compared between the two groups.ResultsA total of 202 patients were analyzed after propensity score matching. There were no differences in baseline characteristics. The median follow-up duration was 62 months (interquartile range, 46–87). There was no difference in the 3-year disease-free survival rate between the PCRT and US groups (83 vs. 88%, respectively; p=0.326). Likewise, there was no significant difference in the 3-year OS (89 vs. 91%, respectively; p=0.466). The 3-year locoregional recurrence rates (3 vs. 2% with US, p=0.667) and distant metastasis rates (16 vs. 11%, p=0.428) were not significantly different between the two groups. Time to completion of curative treatment was significantly shorter in the US group (132 days) than in the PCRT group (225 days) (p<0.001).ConclusionUsing MRI-guided selection for better risk stratification, US without neoadjuvant therapy can be considered in early stage patients with good prognosis. PCRT may not be required for all stage II/III rectal cancer patients, especially for the MRI-proven intermediate-risk group (cT1-2/N1, cT3N0) without CRM involvement and lateral lymph node metastasis. Further prospective studies are warranted.

Outcomes of extensive surgeries in combination treatment of stage III–IV ovarian cancer

Objective: to evaluate short-term and long-term outcomes of lymph node dissection in patients with stage III–IV ovarian cancer.Materials and methods. This retrospective study included patients with stage III–IV ovarian cancer who have undergone either complete or optimal cytoreduction. Patients in the experimental group additionally had lymph node dissection, whereas patients in the control group had surgery without lymph node dissection. We evaluated 3‑year relapse-free survival (primary outcome measure), 3‑year overall survival, incidence of intraoperative and postoperative complications, and frequency of lymph node lesions.Results. The study included 272 patients: 43 women in the experimental group and 229 women in the control group. Intraoperative complications were significantly more common in patients who had lymph node dissection compared to those who had cytoreductive surgery alone (37.2 % vs 16.6 % respectively; р = 0.0001). The incidence of postoperative complications did not vary significantly between the groups (27.9 % in the experimental group vs 16.2 % in the control group; р = 0.128). Thirty-three patients (76.7 %) were found to have metastasis in the lymph nodes excised. The three-year overall survival rate was 82.6 % among patients who had lymph node dissection and 75.7 % among patients who had no lymph node dissection (р = 0.306). The three-year relapse-free survival rate was 26.2 % in the experimental group and 38.4 % in the control group (р = 0.858).Conclusions. Systemic lymph node dissection does not improve long-term outcomes and increases the incidence of intraoperative complications in patients with stage III–IV ovarian cancer undergoing complete or optimal cytoreduction.

541P - Upfront radical surgery with total mesorectal excision (TME) versus preoperative chemoradiotherapy followed by TME in clinical stage II/III patients with rectal cancer: A propensity score analysis

BackgroundAlthough the current standard preoperative chemoradiotherapy (PCRT) for stage II/III rectal cancer decreases the risk of local recurrence, it does not improve overall survival and increase the likelihood of preoperative overtreatment, especially in patients without the circumferential resection margin (CRM) involvement. MethodsStage II/III rectal cancer without CRM involvement and lateral lymph node metastasis was radiologically defined by preoperative magnetic resonance imaging (MRI). Patients who received either PCRT followed by TME (PCRT group) or upfront surgery with TME (US group) between 2011 and 2016 were analyzed. We derived cohorts of PCRT group versus US group using propensity-score matching using staging, age, and distance from anal verge). Three-year relapse-free survival rate, disease-free survival (DFS), and overall survival (OS) were compared between two groups. ResultsA total of 221 patients were analyzed after propensity score matching. There were no differences in baseline characteristics. The median follow-up was 75 months (range, 28-101). No difference in 3-year relapse-free survival rate was noted between PCRT and US groups (89% vs 92% with US; P=0.657). Likewise, there was no statistically significant difference in DFS (7.7 years vs 8.0 years with US; P=0.162) and OS (8.1 years vs 8.3 years with US; P=0.431), respectively. The rates of locoregional recurrence (2.9% vs 0% with US, P=0.301) and distant metastasis (7.4% vs 7.1%, P=1.0) at 3-years were not significantly different between two groups. Interestingly, approximately half of patients had pathologic stage I cancer in both groups (56% with PCRT vs 45% with US; P=0.167) and 69% of patients in US group had not received adjuvant treatment, suggesting that upfront surgery without neoadjuvant therapy can be considered in early stage patients with good prognosis. ConclusionsPCRT may not be required for all stage II/III rectal cancer patients, especially for the MRI-based intermediate-risk group (cT1-2/N1, cT3N0) without CRM involvement and lateral lymph node metastasis. Further prospective studies are warranted. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

L’apport de la radio-chimiothérapie concomittante dans la prise en charge du carcinome indifférencié du nasopharynx de l’adulte

L'objectif de l'étude et d'Analyser les caractéristiques épidémiologiques, cliniques, thérapeutiques et évolutives du carcinome indifférencié du nasopharynx de l'adulte. Il s'agit d'une étude cohorte rétrospective portant sur 163 patients âgés de 17 ans et plus, traités pour un carcinome indifférencié du nasopharynx non métastatique. L'âge moyen des patients était de 46,5ans, avec un sexe-ratio de 1,7. 35,57% des patients étaient atteints de tumeurs localement évoluées (T3-T4) et 52,27% avec une atteinte ganglionnaire régionale avancée (N2-N3). Sur le plan thérapeutique une chimiothérapie neoadjuvante a été réalisée chez 77% des patients et 93,8% des patients ont bénéficié d'une radio-chimiothérapie concomitante. Après un recul moyen de 40,8 mois la survie globale était de 92,9% et la survie sans récidive (SSR) était de 78,9%. L'analyse de la survie sans récidive SSR en fonction des différents facteurs pronostiques a montré une différence statistiquement significative pour l'atteint ganglionnaire avec des taux de SSR à trois ans de 88%, 82,6%, 80,8% et 61,5% en cas de tumeur classée N0, N1, N2 et N3 respectivement (p = 0,02). Le cancer du nasopharynx est une maladie complexe, mais des progrès ont été accomplis grâce à des percées en radiothérapie et en biologie moléculaire. La radio-chimiothérapie concomitante représente le standard thérapeutique des stades cliniques supérieur ou égal à T2, ou supérieur ou égal à N1. Les techniques innovantes d'irradiation semblent prometteuses et pourraient pallier aux problèmes de toxicité tardive tout en assurant un excellent taux de contrôle local.

PREOPERATIVE SHORT-COURSE RADIOTHERAPY COMBINED WITH CHEMOTHERAPY, LOCAL HYPERTHERMIA AND DELAYED SURGERY IN TREATMENT OF RECTAL CANCER: PHASE II TRIAL

Objective : to evaluate efficacy and safety of the short-course radiotherapy combined with capecitabine chemotherapy, intracavitary hyperthermia and delayed surgical treatment as neoadjuvant therapy of rectal cancer Materials and methods . Patients with T2–3N0–2M0 newly diagnosed rectal cancer were included. All patients received short-course radiotherapy with total dose of 25 Gy in several fractions of 5 Gy each, along with capecitabine and metronidazole therapy and local hyperthermia. Capecitabine (1000 mg/m2 ) was administrated twice daily on days 1–14. Local hyperthermia (41–45 °С, 60 min) was applied on days 3–5. Metronidazole (10 g/m2 per rectum) was given on days 3 and 5. Patients underwent surgical treatment not earlier than 4 weeks after neoadjuvant therapy completion. The primary endpoint of the study was assessment of pathologic complete response rate. Secondary endpoints included evaluation of neoadjuvant treatment toxicity, tumor regression, surgical treatment results and oncological results. Results . 81 patients were enrolled. 10 of them (12.3 %) were found to have grade III toxicity, 1 (1.2 %) – grade IV toxicity. Sphincter preservation surgery was carried out in 78 (96.3 %) patients. Postoperative mortality was 0 %. Postoperative complications were registered in 11 (13.8 %) cases. Pathologic complete responses (pCR) were observed in 16 (19.8 %) patients. Median follow-up time was 40.9 months. Distant metastases developed in 10 (12.3 %) patients. Three-year overall survival rate was 97 %, three-year relapse-free survival rate was 85 %. Conclusion. Short-course radiotherapy combined with chemotherapy, radiomodificators and delayed surgical treatment is a safe method for rectal cancer treatment; its results are comparable with the results of prolonged chemoradiotherapy course in terms of tumor regression frequency.

Efficacy of neoadjuvant therapy with trastuzumab concurrent with anthracycline‐ and nonanthracycline‐based regimens for HER2‐positive breast cancer

The aim of this study was to evaluate the pathologic complete response (pCR) rates and relapse-free survival (RFS) and overall survival (OS) of patients receiving neoadjuvant systemic therapy (NST) with trastuzumab in combination with an anthracycline- or nonanthracycline-based regimen. In this retrospective nonrandomized study, the authors reviewed records of 300 patients with HER2-positive breast cancer treated with either sequential paclitaxel and trastuzumab and FEC75 in combination with trastuzumab (PH-FECH) or docetaxel, carboplatin, and trastuzumab (TCH). The Kaplan-Meier product-limit method was used to estimate RFS and OS rates. Logistic regression models and Cox proportional hazards models were fit to determine the associations between NST, pCR, and survival. There was no significant difference in the decline in cardiac ejection fraction; however, patients who received PH-FECH had fewer cardiac comorbidities at baseline (P = .002). pCR rates were 60.6% and 43.3% for patients who received PH-FECH (n = 235) and TCH (n = 65), respectively (P = .016). Patients who received PH-FECH were 1.45 times more likely to have a pCR (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.06-1.98; P = .02). Three-year RFS rates were 93% and 71% (P < .001), and 3-year OS rates were 96% and 86% (P = .008) for patients who received PH-FECH and TCH, respectively. Patients who received PH-FECH had a lower risk of recurrence (hazard ratio [HR], 0.27; 95% CI, 0.12-0.60; P = .001) and death (HR, 0.37; 95% CI, 0.12-1.13; P = .08) than those treated with TCH. The type of NST in HER2-positive breast cancer is predictive of pCR rate independent of disease and patient characteristics. Although TCH is active, PH-FECH shows a higher pCR rate and RFS advantage.

Efficacy of neoadjuvant therapy with trastuzumab concurrent with anthracycline- and nonanthracycline-based regimens for HER2-positive breast cancer.

532 Background: To evaluate the pathologic complete response (pCR) rates and relapse-free survival (RFS) and overall survival (OS) of patients receiving neoadjuvant systemic therapy (NST) with trastuzumab in combination with an anthracycline- or a nonanthracycline-based regimen. Methods: We reviewed records of 300 patients with HER2-positive breast cancer treated with either sequential paclitaxel and trastuzumab and FEC75 in combination with trastuzumab (PH-FECH) or docetaxel, carboplatin, and trastuzumab (TCH). The Kaplan-Meier product-limit method was used to estimate RFS and OS rates. Logistic regression models and Cox proportional hazards models were fit to determine the associations between NST, pCR, and survival. Results: pCR rates were 60.6% and 43.3% for patients who received PH-FECH (n=235) and TCH (n=65), respectively (p=0.016). Patients who received PH-FECH were 1.45 times more likely to have a pCR (Odds ratio [OR]:1.45; 95% confidence interval (CI):1.06-1.98; P=0.02). At a median follow-up of 26.8 months for survivors, there were 28 recurrences and 15 deaths. Three-year RFS rates were 93% and 71% (P<0.001), and 3-year OS rates were 96% and 86% (p=0.008) for patients who received PH-FECH and TCH, respectively. Patients who received PH-FECH had a lower risk of recurrence (hazard ratio [HR]:0.27; 95% CI:0.12-0.60; p=0.001) and death (HR:0.37; 95% CI:0.12-1.13; p=0.08) than those treated with TCH. Conclusions: The type of NST in HER2-positive breast cancer is predictive of pCR rate independent of disease and patient characteristics. While TCH is active, trastuzumab combined with a taxane and then with an anthracycline (PH-FECH) shows a higher pCR rate and a RFS advantage.

Neuronal Apoptosis Inhibitory Protein is Overexpressed in Patients with Unfavorable Prognostic Factors in Breast Cancer

Neuronal apoptosis inhibitory protein (NAIP) is a recently identified inhibitor of apoptosis protein. However, the clinical relevance of NAIP expression is not completely understood. In an attempt to determine the clinical relevance of NAIP expression in breast cancer, the levels of NAIP and survivin expression were measured in 117 breast cancer samples and 10 normal breast tissues using quantitative reverse-transcriptase-polymerase chain reaction. While there was no evidence of NAIP expression in the normal breast tissue, NAIP was expressed in all breast cancer samples. The level of NAIP expression in breast cancer was significantly higher (257 times) than in the universal tumor control. There was a strong correlation between the level of NAIP expression and the level of survivin expression (p=0.001). The level of NAIP expression in patients with a large tumor (≥T2) and patients with an unfavorable histology (nuclear grade III) was significantly higher than in those patients with a small tumor (T1) and patients with a favorable histology (nuclear grade I, II) (p=0.026 and p=0.050, respectively). Although the level of NAIP expression was higher in patients with other unfavorable prognostic factors, it was not significant. The three-year relapse-free survival rate was not significantly the patients showing high NAIP expression and patients showing low NAIP expression (86.47±4.79% vs. 78.74±6.57%). Further studies should include the expressions of NAIP in a larger number of patients and for a longer period of follow-up to evaluate correlation with metastasis and treatment outcome. In conclusion, NAIP is overexpressed in breast cancer patients with unfavorable clinical features such as stage and tumor size, suggesting that NAIP would play a role in the disease manifestation.

Adjuvant oral uracil and tegafur (UFT) improves survival after complete mesorectal excision (ME) for pathologic TNM stage III rectal cancer (RC): Results of the National Surgical Adjuvant Study (NSAS)-Colorectal Cancer (CC) 01 randomized trial

3524 Background: Optimal surgery and optimal adjuvant therapy for stage III RC have not been established yet. Although ME and preoperative radiotherapy are becoming standard practices for RC in the Western countries, ME for clinical stage I RC and ME with extended lateral pelvic lymph node dissection (ELPLND) for clinical stage II or III RCs have been standard practices in Japan. Methods: NSAS-CC01 is a randomized trial comparing postoperative adjuvant oral UFT (400 mg/m2/day for 5 days every 7 days for 1 year) after complete ME, versus complete ME alone in terms of relapse-free survival (RFS) and overall survival (OS). The patients who underwent ME or ME plus ELPLND with microscopic negative margins for pathologic stage III RC (PS 0–2, age 20–75 years, no other adjuvant therapy) were eligible for this trial. Extent of resection was determined by preoperative and intraoperative assessments of tumor location and stage according to the guidelines of the Japanese Society for Cancer of the Colon and Rectum. Extent of resection was documented, and pathologic examination was done according to the guidelines. Results: During 1996 to 2001, 276 (140 UFT, 136 surgery alone) patients were allocated from 28 institutions using a randomization center. Pretreatment characteristics were well balanced between the two groups; median age 58 years, male in 60%, the lower RC in 40%, pT3/T4 RC in 80%, ME with ELPLND in 38% of patients. 75% UFT patients completed more than 84% of scheduled doses. Grade 2 and Grade 3 events were observed in 65% and 17% of UFT patients, respectively. Due to them, 18 patients (13%) stopped UFT intake. Planned interim analysis in 2003 (median follow-up: 3 years) revealed significant prolongation of RFS (P=0.001) and OS (P=0.005) in the UFT group. Three-year RFS rate and OS rate were 78% and 91% in the UFT group, and 60% and 81% in surgery-alone group, respectively. Local recurrence rates were low in both groups (UFT 6%, surgery alone 10%). Conclusions: Adjuvant oral UFT improves survival after complete ME for pathologic stage III RC. No significant financial relationships to disclose.

Analysis of Cdc2 and Cyclin D1 Expression in Breast Cancer by Immunoblotting.

Cyclins and cyclin-dependent kinases may reflect the status of cell proliferation in cancer tissues. The authors sought to determine whether cdc2 and cyclin D1 are expressed in breast cancer and are useful as prognostic factors. Accumulation of cdc2 and cyclin D1 proteins was examined in 88 cases of breast cancer using immunoblotting techniques and correlations with clinicopathological factors and prognoses were investigated. Cdc2 and cyclin D1 proteins were observed in 27.3 % and 75.0 % of breast cancers studied, respectively. The incidence of lymph node metastasis was significantly high in cdc2/cyclin D1-double positive group and low in double negative group. On the other hand, the incidence of estrogen receptor (ER) negative cases was significantly higher in the cdc2-positive/cyclin D1-negative group. Relapse-free survival times of cdc2-positive cases were significantly shorter than those of Cdc2-negative cases. The relapse-free survival times of cyclin D1-positive cases also tended to be poorer than those of cyclin D1-negative cases. Multivariate analyses revealed cdc2 as the second most significant of the prognostic variables, following lymph node status. The three-year relapse-free survival rate of cdc2/cyclin D1-double positive cases was 58.9%, whereas that of cdc2/cyclin D1-doublue negative cases was 100%. Cdc2 and cyclin D1 represent the status of cell proliferation in breast cancer, and may be useful in breast cancer assessment.

Three-year relapse-free survival rates in childhood rhabdomyosarcoma of the head and neck: report from the Intergroup Rhabdomyosarcoma Study.

In 202 patients with rhabdomyosarcoma of the head and neck who registered in the first Intergroup Rhabdomyosarcoma Study, the primary lesions arose about the eye and orbit in 26%, in parameningeal sites in 46%, and in other head and neck areas in 28%. Histopathologically, 78% were embryonal-botryoid, 9% alveolar, 10% undifferentiated, and 3% extraosseous Ewing's types. Actual three-year relapse-free survival rates were calculated from data on 103 of these patients who were free of distant metastases at diagnosis and in whom follow-up had been completed for a three-year period. The actual relapse-free survival rates were 91% (21/23) for those with eye/orbit primaries, 46% (20/44) for those with parameningeal primaries, and 75% (27/36) for those with other head and neck sites affected. Among those with no clinical evidence of tumor activity at two years, 8% (6/75) had subsequent relapses.