The effect of prophylactic cranial irradiation (PCI) for young stage III NSCLC patients: Subgroup analyses of the NVALT-11/DLCRG-02 study

Background: The NVALT-11/DLCRG-02 phase III study compared PCI to observation after chemo-radiotherapy (RT) for stage III NSCLC and showed a significant decrease in the cumulative incidence of symptomatic brain metastases (BM) in the PCI arm at two years (7% vs 27% [HR 0.23]). We here performed exploratory subgroup analyses. Methods: Two year cumulative incidence rates were calculated and competing risk regression, with death of any cause as competing risk, was used to examine the time to symptomatic BM in the following subgr

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus palliative systemic chemotherapy in stomach cancer patients with peritoneal dissemination, the study protocol of a multicentre randomised controlled trial (PERISCOPE II)

Background: At present, palliative systemic chemotherapy is the standard treatment in the Netherlands for gastric cancer patients with peritoneal dissemination. In contrast to lymphatic and haematogenous dissemination, peritoneal dissemination may be regarded as locoregional spread of disease. Administering cytotoxic drugs directly into the peritoneal cavity has an advantage over systemic chemotherapy since high concentrations can be delivered directly into the peritoneal cavity with limited systemic toxicity. The combination of a radical gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in patients with gastric cancer in Asia. However, the results obtained in Asian patients cannot be extrapolated to Western patients. The aim of this study is to compare the overall survival between patients with gastric cancer with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with palliative systemic chemotherapy, and those treated with gastrectomy, CRS and HIPEC after neoadjuvant systemic chemotherapy. Methods: In this multicentre randomised controlled two-armed phase III trial, 106 patients will be randomised (1:1) between palliative systemic chemotherapy only (standard treatment) and gastrectomy, CRS and HIPEC (experimental treatment) after 3–4 cycles of systemic chemotherapy.Patients with gastric cancer are eligible for inclusion if (1) the primary cT3-cT4 gastric tumour including regional lymph nodes is considered to be resectable, (2) limited peritoneal dissemination (Peritoneal Cancer Index < 7) and/or tumour positive peritoneal cytology are confirmed by laparoscopy or laparotomy, and (3) systemic chemotherapy was given (prior to inclusion) without disease progression. Discussion: The PERISCOPE II study will determine whether gastric cancer patients with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with systemic chemotherapy, gastrectomy, CRS and HIPEC have a survival benefit over patients treated with palliative systemic chemotherapy only. Trial registration: clinicaltrials.gov NCT03348150; registration date November 2017; first enrolment November 2017; expected end date December 2022; trial status: Ongoing

Radiation therapy in early stage Hodgkin's disease: long-term results and adverse effects

INTRODUCTION: Radiation therapy (RT) was the first treatment modality demonstrating cure of Hodgkin's disease. Long-term side-effects of this treatment, however, have become evident in the past few years. PATIENTS AND METHODS: By reviewing the results of megavoltage radiotherapy as initial treatment in a consecutive series of 106 patients with early-stage Hodgkin's disease (HD), survival, relapse-free interval, salvage rate of relapsing cases, and incidence of second tumours were evaluated. RESULTS: Subtotal node irradiation was given to all patients with supradiaphragmatic disease, except for 15 patients with limited stage IA-IIA, who received mantle field treatment only. Inverted Y field irradiation was given to all seven patients with subdiaphragmatic disease. The median age was 32 years (range 14-77). The median follow-up was 140 months. The relapse-free interval of the patient population was 78% at 5 years and 72% at 10 years. The overall survival (OS) was 90% and 79%, respectively. Salvage therapy was successful in 26 of 30 relapsing patients. Twelve recurrences were located inside the treatment field. Sixteen patients (15%) developed second malignancies: cancer of the lung (two), ovary (two), cervix (one), colon (two), breast (three), stomach (one), skin (two), hypopharynx (one), and non-Hodgkin lymphoma (two). Eleven of these were located within the radiation field. CONCLUSION: Although RT is intended to be a curative treatment, up to 30% recurrences occur. Mortality was not determined by primary HD, but by second malignancies, which are likely related to treatment. New treatment strategies, aiming at long-term freedom from relapse without carcinogenic side-effects, are urgently needed

High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer

BACKGROUND: The use of high-dose adjuvant chemotherapy for high-risk primary breast cancer is controversial. We studied its efficacy in patients with 4 to 9 or 10 or more tumor-positive axillary lymph nodes. METHODS: Patients younger than 56 years of age who had undergone surgery for breast cancer and who had no distant metastases were eligible if they had at least four tumor-positive axillary lymph nodes. Patients in the conventional-dose group received fluorouracil, epirubicin, and cyclophosphamide (FEC) every three weeks for five courses, followed by radiotherapy and tamoxifen. The high-dose treatment was identical, except that high-dose chemotherapy (6 g of cyclophosphamide per square meter of body-surface area, 480 mg of thiotepa per square meter, and 1600 mg of carboplatin per square meter) with autologous peripheral-blood hematopoietic progenitor-cell transplantation replaced the fifth course of FEC. RESULTS: Of the 885 patients, 442 were assigned to the high-dose group and 443 to the conventional-dose group. After a median follow-up of 57 months, the actuarial 5-year relapse-free survival rates were 59 percent in the conventional-dose group and 65 percent in the high-dose group (hazard ratio for relapse in the high-dose group, 0.83; 95 percent confidence interval, 0.66 to 1.03; P=0.09). In the group with 10 or more positive nodes, the relapse-free survival rates were 51 percent in the conventional-dose group and 61 percent in the high-dose group (P=0.05 by the log-rank test; hazard ratio for relapse, 0.71; 95 percent confidence interval, 0.50 to 1.00). CONCLUSIONS: High-dose alkylating therapy improves relapse-free survival among patients with stage II or III breast cancer and 10 or more positive axillary lymph nodes. This benefit may be confined to patients with HER-2/neu-negative tumor

18FDG positron emission tomography versus 67Ga scintigraphy as prognostic test during chemotherapy for non-Hodgkin's lymphoma

A prospective study was performed, comparing gallium scintigraphy ( 67Ga) and positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (18FDG), to monitor the response of aggressive non-Hodgkin's lymphoma during treatment. 67Ga and 18FDG scans were performed in 26 patients after two cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) therapy. The scans were reviewed independently by four experienced nuclear physicians, who were blinded for the alternative scan technique and follow-up. Eleven out of 26 patients remained free from progression with a mean follow up of 25 ± 5 months, whereas 14 patients relapsed, and one died of lung cancer. Interobserver variation was significantly greater for 67Ga than for 18FDG PET. Some 64% of patients who had a negative early restaging 18FDG PET remained free from progression versus 50% of patients with negative 67Ga scans. Only 25% of patients with a positive PET remained disease free versus 42% of 67Ga-positive patients. Time to progression was associated with 18FDG PET results, but not with those by 67Ga. 18FDG PET had better test characteristics than 67Ga for the evaluation of early response in aggressive non-Hodgkin's lymphoma patients

Predicting early failure after adjuvant chemotherapy in high-risk breast cancer patients with extensive lymph node involvement

PURPOSE: There is limited knowledge of risk factors for breast cancer recurrence within 2 years. This study aimed to predict early failure and identify high-risk patients for prognostic and therapeutic purposes. EXPERIMENTAL DESIGN: We studied 739 patients from a randomized trial who were /=4 or more positive lymph nodes, no distant metastases, and no previous other malignancies. After complete surgical treatment, patients received conventional-dose anthracycline-based chemotherapy or a high-dose scheme of anthracycline-based plus alkylating chemotherapy. We assessed clinical and (immuno)histological parameters to predict recurrence within 2 years. RESULTS: Early failure occurred in 19% (n = 137). Median survival after early failure was limited to 0.7 year. Estrogen and progesterone receptor negativity and visceral relapse predicted poor prognosis. Early failure was associated with young age, large tumors, high histological grade, angio-invasion, apical node metastasis, and >/=10 involved nodes. Estrogen receptor, progesterone receptor, and p27 negativity; HER2 overexpression; and p53 positivity also predicted early failure. The surgical or chemotherapy regimen and histological type did not. The same parameters except tumor size were associated with early death. Grade III, >/=10 involved nodes, and estrogen receptor negativity were independently associated with early failure and together identified a subset of patients (7%) with 3-fold increased early failure and 5-fold increased early death. CONCLUSIONS: Early failure is associated with poor survival. The combination of three commonly determined parameters constitutes a strong predictive model for early failure and deat

Patterns of Hearing Loss in Irradiated Survivors of Head and Neck Rhabdomyosarcoma

Purpose: The frequency and patterns of HL in a HNRMS survivor cohort were investigated. A dose–effect relationship between the dose to the cochlea and HL was explored. Methods: Dutch survivors treated for HNRMS between 1993 and 2017 with no relapse and at least two years after the end of treatment were eligible for inclusion. The survivors were evaluated for HL with pure-tone audiometry. HL was graded according to the Muenster, Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and International Society for Paediatric Oncology (SIOP) classification. We defined deleterious HL as Muenster ≥ 2b, CTCAE ≥ 2, and SIOP ≥ 2. Mixed-effects logistic regression was used to search for the dose–effect relationship between the irradiation dose to the cochlea and the occurrence of HL. Results: Forty-two HNRMS survivors underwent pure-tone audiometry. The Muenster, CTCAE and SIOP classification showed that 19.0% (n = 8), 14.2% (n = 6) and 11.9% (n = 5) of survivors suffered from HL, respectively. A low-frequency HL pattern with normal hearing or milder hearing loss in the higher frequencies was seen in four survivors. The maximum cochlear irradiation dose was significantly associated with HL (≥Muenster 2b) (p = 0.047). In our series, HL (≥Muenster 2b) was especially observed when the maximum dose to the cochlea exceeded 19 Gy. Conclusion: HL occurred in up to 19% of survivors of HNRMS. More research is needed on HL patterns in HNRMS survivors and on radiotherapy dose–effect relationships

The role of local therapy in the treatment of solitary melanoma progression on immune checkpoint inhibition: A multicentre retrospective analysis

Introduction: In patients with metastatic melanoma, progression of a single tumour lesion (solitary progression) after response to immune checkpoint inhibition (ICI) is increasingly treated with local therapy. We evaluated the role of local therapy for solitary progression in melanoma. Patients and methods: Patients with metastatic melanoma treated with ICI between 2010 and 2019 with solitary progression as first progressive event were included from 17 centres in 9 countries. Follow-up and survival are reported from ICI initiation. Results: We identified 294 patients with solitary progression after stable disease in 15%, partial response in 55% and complete response in 30%. The median follow-up was 43 months; the median time to solitary progression was 13 months, and the median time to subsequent progression after treatment of solitary progression (TTSP) was 33 months. The estimated 3-year overall survival (OS) was 79%; median OS was not reached. Treatment consisted of systemic therapy (18%), local therapy (36%), both combined (42%) or active surveillance (4%). In 44% of patients treated for solitary progression, no subsequent progression occurred. For solitary progression during ICI (n = 143), the median TTSP was 29 months. Both TTSP and OS were similar for local therapy, ICI continuation and both combined. For solitary progression post ICI (n = 151), the median TTSP was 35 months. TTSP was higher for ICI recommencement plus local therapy than local therapy or ICI recommencement alone (p = 0.006), without OS differences. Conclusion: Almost half of patients with melanoma treated for solitary progression after initial response to ICI had no subsequent progression. This study suggests that local therapy can benefit patients and is associated with favourable long-term outcomes. & ordf; 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)