Disease-free Survival Figures Research Articles

Is access to adjuvant treatments prioritized over therapies for metastatic cancer? The Israeli experience.

e18599 Background: The Israeli National Insurance Law determines a uniform benefits package ('the Health Basket') for all residents. A public committee advises each year on which new medications should be added to the Health Basket, subject to the fixed annum budget allocated by the government for this purpose. The clinical benefit of the proposed health technologies is the committee's prime consideration; however, the committee also considers the professional medical societies' prioritizations, the expected budget impact, and other social and ethical aspects. Towards the annual discussions for 2023, 63 new indications for 41 cancer drugs were proposed for the annual update. Of those, 8 were for novel neo-adjuvant/ adjuvant indications, all given high priority ranks by the Israeli Oncologists Society based on the significant disease-free survival (DFS) figures from the phase III clinical trials. Varying the adjuvant treatment practice patterns based solely on DFS figures without available overall survival (OS) data has been in much debate recently between global key opinion leaders. We, therefore, aimed to evaluate whether the Israeli decision-makers have de-facto accepted the attitude of prioritizing budgets for adjuvant/neo-adjuvant therapies as the Israeli Oncologists Society recommended. Methods: We collected data on all cancer therapies proposed for inclusion in the 2023 Health Basket update; drug name, indication, treatment setting (curative intent vs. metastatic disease therapy), ESMO-MCBS grade, and whether or not accepted for reimbursement. All data were extracted from the official Israeli Ministry of Health website publications and press releases. Results: 20% of the allocated budget for updating the National Health basket for 2023 was provided to treat solid tumor cancers. 7 out of the 8 candidate therapies in the neo-adjuvant/adjuvant settings received reimbursement approval (88%) vs. 11 out of 55 therapies for advanced/ metastatic stages of disease (20%). 13 of the 16 candidate metastatic disease therapies that had a high ESMO-MCBS score (4 or 5) were not approved for reimbursement in the 2023 annual committee discussions. Conclusions: Our retrospective evaluation of the Israeli reimbursement prioritization process reveals that decision-makers have accepted the approach of prioritizing potentially curative adjuvant therapies over treatments for patients with incurable cancer. In an era of prosperity of adjuvant therapies in a range of tumor types, concerns might arise regarding restrictions on access to novel therapies for metastatic cancer, even those with proven benefits of significantly improving patients' OS and quality of life. Future analysis should determine the impact of this trend adopted by decision-makers in Israel on disease progression and overall survival in the real-world setting.

Strength of ER-positivity in relation to survival in ER-positive breast cancer treated by adjuvant tamoxifen as sole systemic therapy

Aims Oestrogen receptor (ER) positivity has been shown to be a predictive factor for response to endocrine treatment in breast cancer patients. Following breast surgery, adjuvant treatment is allocated according to various parameters (including Nottingham Prognostic Index (NPI), menopausal status and ER status). Patients whose cancer falls in the same NPI range may receive different adjuvant treatment according to ER status. The aim of our study is to assess whether the degree of ER-positivity, as measured immuno-histochemically by H-score (see definition in “ Introduction” section) and percentage of ER-stained cells) has an influence on overall survival (OS) and disease-free survival (DFS) and whether this could be used to help determine adjuvant treatment. Materials and methods A review was undertaken of 563 post-menopausal patients receiving adjuvant tamoxifen and no chemotherapy following surgical resection of histologically proven ER-positive breast cancer. The impact of both H-score and percentage of cells staining for ER was assessed using OS and DFS over a 10-year period. Results Patients were stratified into 4 groups according to ER H-score, namely those scoring ≤50, 51–100, 100–200, and >200. Ten-year survival was 84% for H-score above 200, 67% for H-score 100–200, 71% for H-score 50–100 and 41% for H-score less than 50 ( p < 0.001). Ten-year disease-free survival figures were similar, being 84% for H-score above 200, 73% for H-score 100–200, 83% for H-score 51–100 and 28% for H-score less than 50 ( p < 0.0001). Conclusions The data suggests that patients whose tumours only weakly manifest ER ( H-score ≤50) fare less well in the long-term than patients whose tumours show more vigorous ER-staining when treated by endocrine therapy as sole systemic adjuvant treatment. This finding is relevant to decisions about adjuvant systemic therapy.

The Gene Expression Changes of Oligodendrocytes In Vitro After 10 Gy Irradiation Within 4 Hours

Results: Eighty-eight patients were registered under the diagnoses MBC or TN during the period studied based on morphology and immunohistochemistry. Of these, 18 patients who had pathology consultation only and were not followed at the institution were excluded. MBC was diagnosed in 22 and TN in 38 of the 70 patients analyzed. There were 39 Hispanic (55.7%), 22 Black (31.4%), 8 Caucasian (11.4%) and 1 Asian (1.4%) patients. Median age was 51 (26–85) years. Median tumor diameter was 4 (0.7–25) cm. Stage distribution was I 14 (20%), II 34 (48.6%), III 18 (25.7%), IV 2 (2.9%) and unknown 2 (2.9%). One (1.4%) patient had surgery only, 11 (15.7%) had surgery and chemotherapy, 7 (10%) had surgery and radiation, 50 (71.4%) had surgery, chemotherapy and radiation, and 1 (1.4%) had surgery and hormonal therapy. Twenty-seven (38.6%) had lumpectomy, 40 (57.1%) had mastectomy and 3 (4.3%) had biopsy only. The median follow-up duration was 19.5 (2.3–126) months. Five and 8-year actuarial overall and disease-free survival figures were 70.9%, 23.6%, 61.5% and 17.7% respectively. Conclusions: This report is one of the few that provides some clinico-epidemiological characteristics on MBC. Our findings showed a larger tumor size at presentation with more advanced stage. Therefore, more patients had mastectomy and chemotherapy. The demographics of the patients studied reflect those of our local population. Further studies with genomic microarray analysis will better define the prognosis and treatment outcome of this population.

A phase III randomized study of misonidazole plus radiation vs. radiation alone for cervix cancer

Background and purpose A randomized-controlled study of radical radiotherapy for cervical cancer with or without the hypoxic sensitizer, misonidazole was conducted from 1981 to 1984 to investigate its therapeutic benefit. Patients and methods Seventy-three patients were accrued from the Princess Margaret Hospital, and St John Regional Cancer Centre and randomized to either misonidazole (MISO, n=39) or placebo (P, n=34) in addition to radiotherapy. MISO was given orally each day 4 h prior to external beam radiation treatment (45 Gy to midplane in 20 daily fractions) at a dose of 0.45 g/m 2, as well as during intra-uterine brachytherapy (40 Gy). Results The 10-year overall survival (OS) for the entire group was 46%, and the disease-free survival (DFS) was 39%. The 10-year OS for patients in the MISO arm was 45%, compared to 49% for the P arm ( P=0.89). The corresponding DFS figures were 36 and 43%, respectively, ( P=0.6). Ten patients (14%) developed severe late complications (grade 3 or 4). The 10-year serious late complication rate was 14% for MISO and 12% for P ( P=0.51). Conclusions Misonidazole failed to improve the outcome of patients with cervix cancer treated with radiotherapy.

The outcome of advanced soft tissue sarcoma patients with complete tumour regression after either chemotherapy alone or chemotherapy plus surgery. The Scandinavian sarcoma group experience

The intensified induction regimens used and the potential use of high-dose consolidation chemotherapy (CT) in advanced soft tissue sarcomas (STS) has focused interest on the outcome of those patients who can achieve complete remission (CR) by current therapy. The files from four institutions with a special interest in STS were studied. 38 adult patients with advanced STS who were converted disease-free by either CT alone ( n = 14) or CT followed by surgery ( n = 24) were found. The median follow-up time was 29 months. The median disease-free survival (DFS) was 18 months and the estimated 2-year DFS 34%. The median disease-specific survival (DSS) was 40 months and the estimated 2-year DSS 78%. For patients who achieved CR by CT alone, and for patients who were converted to CR by surgery, the corresponding DFS figures were 23 months (estimated 2 year DFS 48%) and 10 months (26%) ( P = 0.07), respectively. The histological response to CT significantly predicted outcome in patients subjected to surgery (DFS P value 0.004, DSS P value 0.02). Patients who achieved CR by surgery shortly after having achieved a clinical partial response (PR with early surgery) did better than those who where converted to CR by surgery after protracted CT following a clinical PR (PR with late surgery) (DFS P value 0.02, DSS P value 0.1). Our results confirm that CT alone can induce prolonged DFS in rare patients with advanced STS. In patients subjected to surgery, a good histological response indicates improved outcome.

The Outcome of Advanced Soft Tissue Sarcoma Patients with Complete Tumour Regression after either Chemotherapy Alone or Chemotherapy Plus Surgery. The Scandinavian Sarcoma Group Experience

<h2>Abstract</h2> The intensified induction regimens used and the potential use of high-dose consolidation chemotherapy (CT) in advanced soft tissue sarcomas (STS) has focused interest on the outcome of those patients who can achieve complete remission (CR) by current therapy. The files from four institutions with a special interest in STS were studied. 38 adult patients with advanced STS who were converted disease-free by either CT alone (<i>n</i> = 14) or CT followed by surgery (<i>n</i> = 24) were found. The median follow-up time was 29 months. The median disease-free survival (DFS) was 18 months and the estimated 2-year DFS 34%. The median disease-specific survival (DSS) was 40 months and the estimated 2-year DSS 78%. For patients who achieved CR by CT alone, and for patients who were converted to CR by surgery, the corresponding DFS figures were 23 months (estimated 2 year DFS 48%) and 10 months (26%) (<i>P</i> = 0.07), respectively. The histological response to CT significantly predicted outcome in patients subjected to surgery (DFS <i>P</i> value 0.004, DSS <i>P</i> value 0.02). Patients who achieved CR by surgery shortly after having achieved a clinical partial response (PR with early surgery) did better than those who where converted to CR by surgery after protracted CT following a clinical PR (PR with late surgery) (DFS <i>P</i> value 0.02, DSS <i>P</i> value 0.1). Our results confirm that CT alone can induce prolonged DFS in rare patients with advanced STS. In patients subjected to surgery, a good histological response indicates improved outcome.

Combined modality therapy for mediastinal Hodgkin's disease. Prognostic significance of constitutional symptoms and size of disease.

Combined modality therapy was used in an attempt to increase the complete remission rate and survival of previously untreated patients with Hodgkin's disease. MOPP (nitrogen mustard, vincristine, procabazine, prednisone) chemotherapy was followed by radiotherapy. The median duration of follow-up exceeded 5 years. Complete remissions were achieved in 63 of 71 patients (89%) with mediastinal masses. The actuarial survival of 10 years was 72% for patients with small mediastinal masses (mediastinal mass ratio less than 0.35) and 46% for patients with large mediastinal masses (P less than 0.05). The corresponding disease-free survival figures were 69% and 46%, respectively (P less than 0.05). A small mediastinal mass did not affect prognosis. Systemic symptoms especially affected the prognosis in patients with a large mediastinal mass, since in symptomatic patients the actuarial survival and freedom from relapse were 19%, whereas all asymptomatic patients survived without relapse. In patients with a small mediastinal mass, systemic symptoms had no significant effect on the actuarial survival or disease free survival. Age and stage did not affect the prognosis in patients with large mediastinal masses. It was concluded that MOPP chemotherapy followed by radiotherapy was an adequate treatment for asymptomatic patients with large mediastinal disease. However, in symptomatic patients with large mediastinal masses, this treatment was clearly inadequate.

Stages I and II non-Hodgkin's lymphomas of Waldeyer's ring and the neck.

In a previous communication we reported our results for patients with localized extranodal presentations of non-Hodgkin's lymphomas of the head and neck who were admitted between 1961-1969. This review describes our larger experience from 1947-1982 in treating 137 Stages I and II Waldeyer's ring patients whose slides were available for reclassification according to the modified Rappaport System. All of these patients were treated definitively as follows: radiotherapy only, 113 patients; radiotherapy and combination chemotherapy, 17 patients; chemotherapy only, seven patients. The overall 5-year survival was 50%. Significant differences were determined for specific subgroups. For patients staged after lymphangiography, the 5-year survival was 67% as compared with 32% for non-lymphangiogram staged patients (p = 0.002). Stage (Ann Arbor) also influenced results. The 5-year survival figure for Stage I was 70% as compared with 42% for Stage II (p = 0.002). The combination of extent of disease in Waldeyer's ring and the status of the neck had a major impact on survival. When the disease was staged according to the TNMAJCC System, the 5-year survivals were: 75% for T1-T2-TX N0; 53% for T1-T2-TX N+; 54% for T3-T4 N0; and 36% for T3-T4 N+. Also, results for tonsil (52%) and base of tongue (66%) disease were better than for disease involving the nasopharynx (39%) or multiple sites (25%). Treatment also influenced survivals and disease-free survivals. The best results were obtained in patients who were treated with radiotherapy and combination chemotherapy. The 5-year survival and disease-free survival figures were 78% and 69%, respectively.

Hodgkin's disease in the elderly. A series of 30 patients aged older than 70 years.

Thirty patients aged older than 70 years formed 6.9% of all cases of previously untreated Hodgkin's disease seen in Bordeaux Cancer Center over a 20-year period. The subtype of mixed cellularity was predominant in this age group (P = 0.00035). One patient received no treatment; 20 patients received primary chemotherapy (14 polychemotherapy); all but 2 of the 18 patients in clinical Stages I or II received radical radiotherapy. Median survival for all patients is 15 months. In five cases the treatment could be held responsible for death. Eleven patients died of Hodgkin's disease within a 36-month period. Five patients are alive and the nine other patients died from other causes. The disease-free survival figures showed that one third of the patients could be considered as cured.

Combined modality therapy in Stage III and Stage IIIE diffuse large cell lymphomas.

Combined modality therapy consisting of CHOP-Bleo (cyclophosphamide, Adriamycin [doxorubicin], vincristine (Oncovin), prednisone, and bleomycin) and limited-field radiotherapy was given to 47 patients with Stage III and IIIE diffuse large cell lymphomas. Overall 5-year survival and disease-free survival figures are 64% and 53%, respectively. Twenty-nine patients achieved and maintained a complete remission during treatment; 92% of these patients are alive at 5 years, and 87% are disease-free. Prognostic factors were assessed for the entire group. Age, "B" symptoms, extranodal involvement, and extensive abdominal involvement had little effect on survival. However, the presence of mediastinal involvement and extensive abdominal involvement was associated with a poor response rate and survival.

Twelve years' experience with irradiation as the primary treatment for breast cancer.

<h2>Abstract</h2> Ninety patients received comprehensive, high-dose, supervoltage teletherapy as the primary treatment for carcinoma of the breast, following a biopsy or a segmental resection. The tumor doses delivered to the breast ranged between 5600 and 7000 rod in six to mine weeks; the draining lymph nodes received tumor doses of 5000 to 7000 rod in six to eight weeks. In five cases, Iridium-192 implants were employed to boost the radiation dose to the breast, and in seven instances a "toilette" mastectomy was performed for residual cancer. Satisfactory local control and cosmetic results were achieved in 86 patients. The patients were followed for 212 to 1212 years. The local control rates were: Stage I, 100%; Stage II, 95%; Stage III, 100%; Stage IV (M-0), 89%; Stage IV (M-1), 100%. The overall disease-free survival figures were. Stage I, 85%; Stage II, 48%; Stage III, 50%; and Stage IV (M-0), 29%. We feel that this approach to the initial management of breast cancer is a practical, useful, and successful substitute for mastectomy when medical or surgical contraindications exist, or when the patient refuses a mastectomy.

The adverse influence of prior transurethral resection on prognosis in carcinoma of prostate treated by radiation therapy

Since 1970, a total of 291 patients with a minimum follow-up of two years have received radical radiation therapy for carcinoma of the prostate. The five and seven year actuarial survival rates are 78% and 67% respectively. The corresponding disease free survival figures are 66 % and 59 %. A comparison in Stages B & C made between those patients who had a needle biopsy to establish the diagnosis and those who had a transurethral resection of the prostate, revealed a vastly different disease free survival: 72 % and 51 % respectively. This is significant at a p value of 0.005. This difference is of greater importance in early Stage B disease than in later stage disease. Several hypotheses are offered to account for these differences, one of which is that the surgical procedure of transurethral resection results in dissemination of the disease.

The management of stage 111a hodgkin's disease

Forty patients with pathological Stage IIIA Hodgkin's disease were allocated to receive either total nodal irradiation (TNI) or 6 cycles of chemotherapy with Nitrogen Mustard (Mustine), Vinblastine, Procarbazine and Prednisolone (MVPP) as initial treatment. The complete remission rate for both groups was 100%, with 5-year actuarial disease-free survival figures of 74 and 87% for TNI and MVPP respectively (median duration of follow-up = 48 months). Eighty-eight per cent of TNI treated patients were alive at 5 years compared with 100% in the MVPP group. Three patients died, two who were treated with TNI and one who received MVPP. Treatment related morbidity included one patient with osteonecrosis and one with a second malignancy. Given the length of follow-up available, these results demonstrate no significant difference between TNI and MVPP for patients with Stage IIIA disease; it is unlikely that further patient entry into this particular study will allow any conclusion to be reached regarding the optimal form of management. We would recommend that individual disease characteristics within Stage IIIA be used as a basis for future treatment decisions with the understanding that further information regarding morbidity may become available with prolonged follow-up.

Radiotherapy in the treatment of Hodgkin's disease.

Eighty-seven untreated patients with localised Hodgkin's disease seen from 1969 to 1975 were treated by megavoltage radiotherapy. All were followed for at least 33 months. Thirty-three patients were staged clinically and 54 underwent more extensive investigation by lapaortomy and splenectomy. The projected five-year disease-free survival figures for patients staged surgically were 100% for the 17 with stage IA disease, 70% for the 19 with stage IIA disease, and 73% for the 15 with stage IIIA disease. These results were consistently better than those obtained in clinically staged patients. Five patients died, one of them without evidence of Hodgkin's disease. As irradiation seems to produce excellent disease-free survival in most patients who are staged accurately at diagnosis, caution should be exercised in the routine use of adjuvant chemotherapy until the full risks of such treatment are clear. Combined modality therapy may be appropriate for patients with unfavourable features at presentation.

Wilms's tumour--an improved prognosis. Report of 22 consecutive children seen from 1967-71.

An unselected series of 22 consecutive children with Wilms's tumour seen during the period 1967-71 is described. The management of the patients consisted of operation, radiotherapy, and chemotherapy in varying combinations. The following guide-lines for treatment are suggested: early operation by a transabdominal approach, abdominal irradiation for most patients, both immediate and maintenance chemotherapy, and aggressive treatment of metastatic disease should it occur. The 2-year disease-free survival figures for this series, in the order of 80%, equals the best previously reported and emphasizes the improved prognosis for children with this tumour.