Inoperable localized stage I and stage II non-small-cell lung cancer

Opinion statement Early stage, medically inoperable non-small-cell lung cancer is a treatable disease. A thorough clinical work-up is necessary to optimize management for this group of patients. Thoracic radiation therapy has been used for such patients with achievement of durable local control and prolonged survival. To improve upon the results of standard fractionation radiation therapy, novel approaches are needed. Dose escalation may further enhance local tumor control and survival rates. Efforts to minimize irradiation to normal lung parenchyma are necessary. Multiple strategies to optimize the therapeutic ratio are being investigated. Elimination of elective nodal irradiation may reduce late toxicity of treatment but may compromise locoregional control. Other strategies, such as intensity-modulated radiation therapy with dose volume histograms will help minimize lung parenchyma irradiation, which will reduce the probability of radiation pneumonitis. Chemotherapy appears to play a minimal role in the treatment of inoperable limited disease, but researchers continue to conduct investigational trials with active chemotherapeutic agents in the hopes of reducing local and distant tumor failures.     

Selenium-enriched garlic inhibits the early stage but not the late stage of mammary carcinogenesis

Previous work has shown that the efficacy of cancer preventionby selenium-enriched garlic (Se-garlic) is primarily dependenton the action of selenium. Additionally, supplementation ofSe-garlic inhibited the post-initiation phase of mammary carcinogenesiswhen it was given continuously to the animals. In this report,experiments were carried out in which treatment with the Se-garlicwas started after carcinogen dosing (DMBA or MNU) but was restrictedto either the early or late stage of neoplastic progression.The results from these two models showed that a short-term exposureto the Se-garlic for 1 month immediately following carcinogenadministration was just as effective in cancer prevention asthe continuous exposure regimen (5 months), suggesting thatthe Se-garlic may irreversibly alter the process of clonal expansionand/or selection of transformed cells during their early stageof development. Plasma and mammary tissue selenium levels essentiallyreturned to basal levels at 1 month after withdrawal of supplementation.These observations imply that the outcome of cancer protectionby short-term Se-garlic intervention was not due to a slow turnover,and therefore a lingering presence, of selenium in the targetorgan or in the circulation. The above finding was in contrastto that of a second study in which Se-garlic was supplementedstarting at 13 weeks after carcinogen treatment With this protocol,the number of new tumors and the number of new tumor-bearingrats found during the intervention period (weeks 13 to 22) werenot statistically different between the control and supplementedgroups, suggesting that Se-garlic had a minimal effect on thelater stages of mammary carcinogenesis.     

Human papillomavirus modifies the prognostic significance of T stage and possibly N stage in tonsillar cancer

BackgroundDespite the association with more advanced nodal stage, patients with human papillomavirus (HPV) positive oropharyngeal cancers have better outcomes. We examined whether the HPV can modify the effect of known prognostic factors in tonsillar cancer.Patients and methodsA total of 489 patients from 10 centres were followed up for recurrence or death for a median of 3.2 years. Determinants of the rate of locoregional recurrence, death from tonsillar cancer and overall survival were modelled using Cox regression.ResultsThe prognostic value of T and N stages were modified by HPV as indicated by statistically significant interaction terms. After adjusting for age, gender and treatment, T stage appeared relevant only for HPV-positive cancers (where a higher T stage was associated with worse outcomes). There was some evidence that N stage was a more relevant prognostic factor for HPV-negative than -positive cancers. There was no evidence that the HPV modifies the effect of age, gender or grade on outcomes.ConclusionsThis study suggests that the prognostic significance of the conventional staging system in tonsillar cancer is modified by HPV.     

The surgical management of stage I and stage II lung cancer

There have been recent advances in the treatment of non-small cell lung cancer (NSCLC). Surgical resection remains the cornerstone in the treatment of patients with stages I and II NSCLC. Anatomic lobectomy combined with hilar and mediastinal lymphadenectomy constitutes the oncologic basis of surgical resection. The surgical data favor video-assisted thoracic surgery (VATS) lobectomy over open lobectomy and have established VATS lobectomy as a gold standard in the surgical resection of early-stage NSCLC. However, the role of sublobar pulmonary resection, either anatomic segmentectomy or nonanatomic wedge resection, in patients with subcentimeter nodules may become important.     

Adjuvant treatment of stage IB NSCLC: the problem of stage subset heterogeneity

While 5-year survival rates in patients with stage IB non-small-cell lung cancer (NSCLC) are historically modest (40% to 67%), adjuvant chemotherapy trials including this subgroup have shown little evidence of chemotherapeutic benefit. This article reviews the available data regarding adjuvant chemotherapy following surgically resected stage IB NSCLC, framed within the context of present and future proposed definitions of this diagnosis. The discussion addresses limitations of the current staging system and how this contributes to the mixed results seen with adjuvant treatment. In addition, the authors consider current treatment options for stage IB NSCLC and review planned clinical trials for stage I disease designed to exploit new pharmacogenomic findings.     

Low stage invasive carcinoma of the uterine cervix stage I-IIA morphological prognostic factors

Histological material was reviewed from the 213 patients who had undergone radical surgery for carcinoma of the uterine cervix stage I and IIA between 1967 and 1981. Squamous carcinoma was found in 179 patients (84.7%). In 39 patients (18%) there were lymph node metastases and in nine (4.2%) tumor spread into the parametrium. Vaso-invasion was present in 49 patients (22%). Prognostic factors were studied by Cox's regression analysis. Lymph node metastases and vaso-invasion were both found to be significantly related to survival rate (P = 0.0001 and P = 0.0008). Stage, cell type, differentiation and invasion depth were of no prognostic importance.     

Leukemic leptomeningeal involvement in stage 0 and stage 1 chronic lymphocytic leukemia

Central nervous system (CNS) involvement in early (Rai Stage 0 and Stage 1) chronic lymphocytic leukemia (CLL) is rare, with only five cases reported. We present the sixth reported case, a 77-year-old male with a 4 year history of Stage 0 CLL who presented with sudden onset of diplopia and headache. Workup revealed a leukemic involvement of his CNS and he responded well to treatment with intrathecal (IT) methotrexate. After his third IT treatment, he developed a change in his mental status, consistent with a chemotherapy induced encephalopathy, which was effectively treated with IT hydrocortisone. In addition to the case presentation, we review the previously reported cases in an effort to determine any characteristics common among the Stage 0/1 CLL patients with reported CNS involvement.     

Surgical adjuvant therapy for stage II and stage III adenocarcinoma and large-cell undifferentiated carcinoma

The Lung Cancer Study Group randomized 141 patients with resected stage II and III adenocarcinoma and large-cell undifferentiated carcinoma to receive postoperative Cytoxan (Bristol-Meyers, Syracuse, NY), Adriamycin (Adria Laboratories, Columbus, Ohio), and cisplatin (CAP) chemotherapy or bacillus Calmette-Guerin (BCG) and levamisole immunotherapy. Careful intraoperative staging was performed on all patients. Before randomization, patients were stratified by stage, weight loss, cardiac arrhythmia, and institution. Prognostic variables such as stage, age, weight loss, and nodal involvement were equally distributed between the two groups. Disease-free survival was significantly prolonged in the group receiving chemotherapy. There was no evidence of a deleterious effect of the immunotherapy. This study indicates that postoperative CAP chemotherapy is effective in prolonging disease-free survival in these patients.     

Intensive postoperative chemoimmunotherapy for patients with stage II and stage III breast cancer

For the past 34 months, a combination of 5-fluorouracil, adriamycin, cyclophosphamide, and BCG (FAC-BCG) was evaluated as adjuvant treatment in stage II and III breast cancer patients with positive axillary nodes. In the group of 131 patients receiving FAC-BCG, the estimated proportion remaining disease-free at 2 years from surgery was 91% compared to an estimated 69% in a group of 151 historical control patients (p less than .01). This advantage was statistically significant in all subgroups except for patients with primary tumor less than 3 cm and for patients with less than 4 positive nodes. Estimated 2-year survival rates were 9,6% for FAC-BCG patients and 86% for control (p = .02). Treatment was well tolerated. Adjuvant FAC-BCG seems effective in prolonging disease-free interval and early survival in patients with stage II and III breast cancer. Its long term efficacy will require longer follow-ups.     

Depression and tumor stage in cancer of the head and neck

A study was undertaken to explore the relationship between depression and tumor invasiveness in a group of 45 patients with cancer of the head and neck at different stages. Patients were assessed for depression at the time of their first visit to a tertiary care cancer center, before definitive diagnosis was made and treatment initiated. Depression was assessed by using the DSM-III derived dysthymia scale of the Millon Clinical Multiaxial Inventory and by clinical interview which elicited symptoms of major depression. We hypothesized that if depression were related to the physical effects of the tumor then patients with more advanced cancer would be more depressed due to associated pain, discomfort and nutritional deficits. Contrary to expectations, results showed that depression scores were distributed equally throughout all stages. However, stage × gender analysis showed a significant effect with females having early stage (1 and 2) cancer being most depressed. Physical symptoms and nutritional factors were not associated with depressed affect but marital status (unmarried) and stress scores were. The high frequency of depression reported in head and neck cancer patients is not necessarily the result of the malignant process or a response to treatment but may be related to premorbid factors of which social support is one variable.     

Carcinoma of the uterine cervix stage IB and early stage II. Prognostic value of the histological tumor regression after initial brachytherapy

In our center limited centro pelvic invasive carcinomas of the uterine cervix (less than 4 cm) are treated with brachytherapy and surgery. With these therapeutic modalities no residual carcinoma was observed for 80% of the patients. The purpose of this study was to evaluate our results with this treatment, and to evaluate the prognostic value of the pathological status of the cervix. From 1976 to 1987 we have treated 115 patients with these modalities. Staging system used was the FIGO classification modified for Stage II (divided in early Stage II and late Stage II). Patients were Stage IB (70 cases) and early Stage II (45 cases); 60 Gy were delivered with utero vaginal brachytherapy before any treatment. Six weeks later a radical hysterectomy with pelvic lymphadenectomy was performed. Twenty-one patients with positive nodes received a pelvic radiotherapy (45 to 55 Gy). Local control rate was 97% (100% for Stage IB and 93% for early Stage II). Uncorrected 10-year actuarial survival rate was 96% for Stage IB and 80% for early Stage II patients. No treatment failure was observed for Stage IB patients. Ninety-two patients (80%) had no residual carcinoma in the cervix (group 1) and 23 patients (20%) had a residual tumor (group 2). The sterilization rate of the cervix was 87% for Stage IB tumors versus 69% for early Stage II, and was 82% for N- patients versus 68% for N+ patients. Ten year actuarial survival rate was 92% for group 1 and 78% for group 2 (p = 0, 1). Grade 3 complications rate was 6%. We conclude that brachytherapy + surgery is a safe treatment for limited centro pelvic carcinomas of the uterine cervix (especially Stage IB) and that pathological status of the cervix after brachytherapy is not a prognostic factor.     

Adjuvant external beam therapy for pathologic stage I and occult stage II endometrial carcinoma

Eighty-six patients with pathologic Stage I or occult Stage II carcinoma of the endometrium and myometrial invasion and/or Grade 2 or Grade 3 histologic condition received whole-pelvis external radiation therapy (RT) after extrafascial total abdominal hysterectomy and bilateral salpingo-oophorectomy. Twenty-one patients received 4250 cGy in 25 daily fractions for 5 weeks (Group 1), 28 received 4500 cGy in 25 daily fractions for 5 weeks (Group 2), and 37 received 5100 cGy in 30 daily fractions for 6 weeks (Group 3). Seventeen patients had intravaginal brachytherapy after whole-pelvis RT. Local recurrence developed in two patients (2.3%) (one in Group 1 and one in Group 2). Statistical analysis showed that the depth of myometrial invasion significantly influenced survival (P = 0.016). Tumor grade, pathologic stage, whole-pelvis radiation dose, and the use of brachytherapy did not influence survival. Complications occurred in 9.5% of patients in Group 1, 24.7% in Group 2, and 40.5% in Group 3. Three patients who received brachytherapy had rectal injuries. The authors conclude that 4250 cGy in 25 fractions for 5 weeks of whole-pelvis RT appears to induce fewer complications than higher doses, and may be sufficient to prevent local recurrence in most patients who require adjuvant RT. A clinical trial is needed to determine the optimum dose-time-fractionation regimen.     

Cancer surgery on the global stage: Updates and progress

Over 5 billion people lack access to basic surgical procedures, and it is estimated, the number of surgical procedures needed for cancer care will increase by 5 million from 2018 to 2040. The greatest increase in demand will occur in low- and middle-income countries. In this article, we highlight progress made in surgical cancer care globally and gaps that still needs to be addressed. We highlight political support, workforce progress and shortages, impact of the COVID-19 pandemic, and the importance of high value cancer care