The staging and treatment of epithelial ovarian cancer.

Recent advances in the staging of ovarian cancer have suggested that many patients with apparently localized (stage I or II) disease have occult dissemination within the abdomen. Approximately 20% of patients classified at laparotomy as having stage I or II ovarian cancer are found by lymphangiography to have abnormal retroperitoneal lymph nodes. In many other patients advanced disease is also detected by peritonescopy; with this technique metastases are often discovered on the undersurface of the right diaphragm. These findings may help explain the high rates of recurrence after surgical resection or pelvic irradiation, or both, in patients with localized disease. Studies are in progress to determine whether modification of the radiotherapy field to include the right diaphragm will improve survival. Along with improved staging, histologic grading of the degree of anaplasia of the tumour tissue may permit more precise determination of prognosis and therefore better design of therapy. Adjuvant radiotherapy has not yet been shown to improve the survival of patients with stage I disease, but the 5-year survival of patients with stage II disease is greater for those receiving postoperative radiotherapy than for those undergoing surgery alone. For most patients with advanced disease radiotherapy is palliative only and carries a high risk of long-term complications. Numerous chemotherapeutic agents used singly can produce an objective response by tumour. Preliminary data suggest that combination chemotherapy can increase the rate of objective response, but a longer follow-up period is necessary to determine whether this form of therapy can improve survival.     

Whole brain radiotherapy: Consequences for personalized medicine

Several studies focusing on brain irradiation are in progress. Reflecting updates of relevant outcomes in palliative treatment of patients suffering from brain metastases, the primary objective of these studies is the evaluation of neurocognitive function and quality of life. Improvements of technology in radiation oncology allows us to spare the hippocampal region while appropriately irradiating other parts of brain tissue. Irradiation of the hippocampus region is likely to lead to manifestations of adverse events with a subsequent impact on patient''s quality of life, which is in fact an improper approach in palliative medicine. Ongoing studies evaluate results of hippocampus avoiding radiotherapy compared to standard whole brain radiotherapy. Incorporation of neurocognitive function assessment may result in the confirmation of superiority of sparing the region of hippocampus and thus change current style of providing brain irradiation.     

Neoadjuvant chemotherapy in head and neck cancer

BACKGROUND: Neoadjuvant chemotherapy has an increasing role in multimodality treatment of advanced head and neck cancer. In this paper we summarize our first results with this treatment. METHOD: Thirty-five, previously untreated, mostly inoperable head and neck cancer patients were given two cycles of Cisplatin and 5FU chemotherapy. We continued the therapy only in case of regression until four cycles, then the patients received surgical and/or radiotherapy according to their status. After the treatment patients' status was regularly evaluated. RESULTS: We detected 4 complete and 20 partial responses after the chemotherapy. Three patients became eligible for a radical operation. At this moment 10 patients are free of tumor, 8 patients died in consequence of the tumor, we have no data in 3 cases, 3 patients are given palliative therapy because of progression, 4 patients are receiving radiotherapy and 7 patients with partial response are candidates for further active oncotherapy. CONCLUSIONS: Although the number of the patients we treated is too small for a statistical analysis, our results are similar to the conclusion of the large randomized studies: after neoadjuvant chemotherapy of advanced head and neck cancer partial response can improve the result of surgical or radiological treatment. Neoadjuvant chemotherapy does not improve survival in advanced head and neck cancer, but it is of great importance because of better quality of life of patients, especially those who had organ preserving therapy.     

Evidence based radiation oncology with existing technology

Aim

To assess the real contribution of modern radiation therapy (RT) technology in the more common tumoral types in Central America, Caribbean and South America.

Background

RT is an essential tool in the management of cancer. RT can be either palliative or of curative intent. In general, for palliative radiotherapy, major technologies are not needed.

Materials and methods

We analyzed the contribution of RT technology based on published evidence for breast, lung, gastric, gallbladder, colorectal, prostate and cervix cancer in terms of disease control, survival or toxicity with especial focus on Latin America.

Results

Findings indicate that three dimensional conformal radiation therapy (3D RT) is the gold standard in most common type of cancer in the studied regions. Prostate cancer is probably the pathology that has more benefits when using new RT technology such as intensity modulated radiation therapy (IMRT) versus 3DRT in terms of toxicity and biochemical progression-free survival.

Conclusions

In light of the changes in technology, the ever-increasing access of developing countries to such technology, and its current coverage in Latin America, any efforts in this area should be aimed at improving the quality of the radiotherapy departments and centers that are already in place.     

The role of radiation therapy for carcinoma of the lung

A large proportion of patients with carcinoma of the lung may benefit from the use of radiation therapy. Operable patients have not been shown to benefit from preoperative irradiation, but postoperative irradiation has improved survival in those found to have involvement of hilar or mediastinal lymph nodes. Radiation therapy is the only potentially curative treatment for patients who are inoperable, but do not have distant metastasis. Control of the local tumor is very dependent upon dose-fractionation-time relationships. Patients who are relatively asymptomatic, i.e., they have a high performance status, are curable if treated promptly with radiation therapy. Small cell carcinoma requires both radiation therapy and chemotherapy. The optimal method of combining the two modalities is yet to be determined, but prophylactic cranial irradiation is necessary to control microscopic metastases that are not affected by systemic chemotherapy, and thoracic irradiation is necessary to give the highest probability of control of the primary tumor. Prophylactic cranial irradiation has also been shown to reduce the frequency of brain metastasis in patients with squamous carcinoma, large cell carcinoma, and adenocarcinoma; it may become more important in these cell types when more effective chemotherapy is developed.     

Lactate-mediated changes in growth morphology and transformation frequency of irradiated C3H 10T1/2 cells

Treatment of mammalian cells with lactate or inhibitors of glycolysis alters their radiation response, particularly in the low dose region of the dose response curve. The occurrence of both high lactate levels and high glycolytic metabolism in tumours is well known and therefore the effect of lactate on a cell line sensitive to radiation induced transformation was examined using a single exposure to Cobalt 60 gamma rays as the carcinogen challenge. The results indicate that cells treated with 5mM lactate before irradiation exhibit changes in morphology and growth rate and that the transformation frequency is increased by three to ten fold following 24 hours lactate treatment just prior to irradiation. Examination of radiation survival curves showed a positive correlation between transformation frequency and size of the shoulder, but increasing transformation frequency was associated with a decrease in Do. A mechanism involving altered Redox potential in lactate treated cells is suggested. The results are discussed in terms of their possible significance for radiotherapy.     

Tratamiento de los adenomas hipofisarios clínicamente no funcionantes

Clinically nonfunctioning adenomas are the most frequent pituitary macroadenomas in adults. These tumors are characterized by the absence of detectable hormonal hypersecretion and are diagnosed when compression symptoms or hormonal deficiencies occur. The treatment of choice of macroadenomas is surgery, but tumoral resection is often incomplete or the patient develops tumoral recurrence. Medical therapy has been shown to produce modest tumoral reduction in some patients. Postoperative irradiation should be considered in patients with large tumoral remnants or enlargement of remnants during follow-up. Stereotactic radiotherapy has been developed to diminish the long-term complications of radiotherapy. Microadenomas tend to remain small and surveillance alone is recommended. The present article reviews the results of medical, surgical and radiation treatments.     

Association between Lymph Node Ratio and Disease Specific Survival in Breast Cancer Patients with One or Two Positive Lymph Nodes Stratified by Different Local Treatment Modalities

Purpose

Results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial indicated that complete axillary node dissection (ALND) may not be warranted in some breast cancer patients with low tumor burden who are undergoing breast-conserving surgery following whole-breast irradiation. However, this study did not address patients undergoing mastectomy or those undergoing breast-conserving surgery without whole-breast radiotherapy. Given that lymph node ratio (LNR; ratio of positive lymph nodes to the total number removed) has been shown to be a prognostic factor in breast cancer, we first sought to determine the prognostic value of LNR in a low risk population comparable to that of the Z0011 trial and further to investigate whether the prognostic significance differs with local treatment modality.

Method

We used the Surveillance Epidemiology and End Results (SEER) database to identify breast cancer patients with T1-T2 tumor and 1–2 positive nodes. Patients were subclassified by the local therapy they underwent for the primary tumor. The prognostic value of LNR in predicting disease-specific survival (DSS) was examined in each treatment group.

Results

A total of 53,109 patients were included. In the subgroup of 20,602 patients who underwent lumpectomy following radiotherapy, LNR was not found to be significantly associated with DSS in both the univariate and multivariate model. For the 4,664 patients treated with mastectomy following radiotherapy, 6,811 treated with lumpectomy without radiotherapy and 21,031 with mastectomy without radiotherapy, LNR independently predict DSS in each of these subgroups.

Conclusions

Our results add evidence to the concept that axillary dissection could be omitted in patients with one or two positive nodes following breast-conserving surgery and whole breast radiation.     

Angiosarcomas of the chest wall and breast after radiotherapy: The questions of radiogenic origin,diagnosis and treatment

PURPOSE: To present medical history of secondary chest wall and breast angiosarcomas (AS) developed after radiotherapy, and to discuss the questions of radiogenic origin, diagnosis and treatment by the review of the literature. METHODS: Report of two cases and MEDLINE search for relevant publications. RESULTS: Secondary AS occured in a previously irradiated field after a long (6 and 8 years) latency period in both cases. Detailed histopathological and immunohistochemical examinations from the biopsy and/or surgical specimens confirmed the diagnosis as AS. The first patient with moderately differentiated AS was treated successfully with radical surgery. The second patient with irresecable AS died of rapid local progression within 4 months. The incidence of chest wall and breast AS is increased after irradiation, however, controversial data exist in the literature. The incidence of chest wall and breast AS after radiotherapy was found to be 0.39% in our patient population, which means an estimated odds ratio of 2.4 for secondary AS. Stewart-Treves syndrome is not of radiogenic origin, since postoperative lymphoedema has been considered as primary etiological factor. CONCLUSIONS: Patients treated with surgery and/or radiotherapy for primary breast cancer are at higher risk for developing secondary AS, compared to the healthy population. An etiological relationship between radiotherapy and subsequent AS of chest wall and breast is likely, but still controversial. Initial radical surgery is the only effective treatment for achieving long term survival. Further adjuvant radiotherapy is no longer feasible, due to the previous irradiation. Chemotherapy has only palliative effect. These very rare cases deserve special attention due to the atypical clinical appearance, difficulties of differential diagnosis and poor prognosis.     

3D radiation therapy or intensity-modulated radiotherapy for recurrent and metastatic cervical cancer: the Shanghai Cancer Hospital experience

We evaluate the outcomes of irradiation by using three-dimensional radiation therapy (3D-RT) or intensity-modulated radiotherapy (IMRT) for recurrent and metastatic cervical cancer. Between 2007 and 2010, 50 patients with recurrent and metastatic cervical cancer were treated using 3D-RT or IMRT. The median time interval between the initial treatment and the start of irradiation was 12 (6-51) months. Salvage surgery was performed before irradiation in 5 patients, and 38 patients received concurrent chemotherapy. Sixteen patients underwent 3D-RT, and 34 patients received IMRT. Median follow-up for all the patients was 18.3 months. Three-year overall survival and locoregional control were 56.1% and 59.7%, respectively. Three-year progression-free survival and disease-free survival were 65.3% and 64.3%, respectively. Nine patients developed grade 3 leukopenia. Grade 5 acute toxicity was not observed in any of the patients; however, 2 patients developed Grade 3 late toxicity. 3D-RT or IMRT is effective for the treatment of recurrent and metastatic cervical cancer, with the 3-year overall survival of 56.1%, and its complications are acceptable. Long-term follow-up and further studies are needed to confirm the role of 3D-RT or IMRT in the multimodality management of the disease.     

Isolated nodal failure after chemo-radiotherapy in limited disease small cell lung cancer (LD-SCLC)

BackgroundThe irradiation volume for treatment of limited disease small cell lung cancer (LD-SCLC), are still controversial. One of the aspects of radiation volume is the use of elective nodal irradiation (ENI), which has never been subjected to randomized study in SCLC patients.AimTo review retrospectively patterns of failure in relation to the radiation field after chemoradiotherapy (CHT-RT) in patients with limited disease small cell lung cancer (LD-SCLC).Material and MethodsBetween 1997 and 2006, 117 consecutive patients with LD-SCLC received chemotherapy with sequential radiotherapy (70%) and concurrent or alternating CHT-RT (30%). All but one case had predefined elective nodal irradiation (ENI) without inclusion of supraclavicular regions. Prophylactic cranial irradiation (PCI) was administered to 39% of patients.ResultsThe median follow-up for the 20 living patients was 33 months. The overall survival at 2 years was 36% (median survival: 18 months). In-field locoregional progression was observed in 42 patients (36%). Distant metastases occurred in 71 patients (61%). Five patients (4%) developed isolated nodal failure (INF) without local progression in the supraclavicular region. Patients with INF had N3 disease more often than those without INF (60% vs 21%, p = 0.04). There was 5% RTOG grade 3 or higher early radiation toxicity.ConclusionsINF failures are rare; however, the need for extension of ENI to supraclavicular areas may be reconsidered in N3 patients.     

Outcome of a multimodal therapy of a recurrent adenocarcinoma arising from Caesarean section scar endometriosis—A case report

Background

Endometriosis occurring in surgical scars is a well-described entity. Malignant transformation of endometriosis is a rare event, with most cases belonging to adenocarcinoma. The initial surgical treatment is a method of choice. Due to lack of therapeutic recommendations, adjuvant therapy and recurrence management are a great challenge for oncologists.

Aim

The aim of this paper was to present a long-term survival as the outcome of multimodal therapy in the patient with recurrent adenocarcinoma arising from Caesarean section scar endometriosis.

Case

We present the case of a woman with recurrent adenocarcinoma arising from Caesarean section scar endometriosis. The disease was first diagnosed in September 1997 at age 43. The patient underwent abdominal hysterectomy with tumour excision. Due to a local recurrence after 4 years, tumour excision with abdominal wall repair using a plastic mesh, regional lymphadenectomy, bilateral salpingo-ovariectomy and adjuvant radiotherapy for the pelvic region with local boost were performed; in addition hormontherapy with medroxyprogesterone was started. Because of a recurrent pelvic tumour, chemotherapy, further local palliative radiotherapy and brachytherapy were administered. Subsequently distant metastases in bilateral axillary lymph nodes were diagnosed and palliative radiotherapy was performed. The patient died of morbus neoplasmaticus generalisatus in September 2008. The follow-up period had been 132 months.

Conclusion

This paper is, to our knowledge, the only report in literature that presents a long-term survival as the outcome of multimodal therapy in the patient with this rare diagnosis. Further reports of new cases can help establish optimal treatment guidelines.     

Literature review of clinical results of total skin electron irradiation (TSEBT) of mycosis fungoides in adults

Background

Mycosis fungoides (MF) is an extranodal, indolent non-Hodgkin lymphoma of T cell origin. Even with the establishment of MF staging, the initial treatment strategy often remains unclear.

Aim

The aim of this study was to review the clinical results of total skin electron beam therapy (TSEBT) for MF in adults published in English language scientific journals searched in Pubmed/Medline database until December 2012.

Results

MF is very sensitive to radiation therapy (RT) delivered either by photons or by electrons. In limited patches and/or plaques local electron beam irradiation results in good outcomes besides the fact of not being superior to other modalities. For extensive patches and/or plaques data suggest that TSEBT shows superior response rates. The cutaneous disease presentation is favorably managed with radiotherapy due to its ability to treat the full thickness of deeply infiltrated skin. For generalized erythroderma presentation, TSEBT seems to be an appropriate initial therapy. For advanced disease, palliation, or recurrence after the first radiotherapy treatment course, TSEBT may still be beneficial, with acceptable toxicity. Recommended dose is 30–36 Gy delivered in 6–10 weeks.

Conclusion

TSEBT can be used to treat any stage of MF. It also presents good tumor response with symptoms of relief and a palliative effect on MF, either after previous irradiation or failure of other treatment strategies.     

The current management of mycosis fungoides and Sézary syndrome and the role of radiotherapy: Principles and indications

Aim

To evaluate the current treatment of mycosis fungoides (MF) and Sézary syndrome (SS) focusing on the role of radiotherapy (RT), its principles and indications, and the perspectives of the novel irradiation technologies.

Background

MF and SS are rare lymphoproliferative diseases whose incidence is increasing. For a long time RT has been used as a single modality or in integrated treatment programs for these diseases.

Materials and methods

The latest systematic reviews, primary studies and new diagnostic and treatment guidelines on MF and SS were analyzed. Clinical outcomes together with the technical aspects and the role of RT were also evaluated.

Results

New data are available on pathogenesis, diagnostic criteria, classification and staging procedures for MF and SS and several local and systemic therapies are proposed. Localized RT can cure “minimal stage” MF while total skin electron beam irradiation (TSEI) may cure initial-stage disease and may offer important symptom relief (itch, erythroderma) in a more advanced setting. Despite its efficacy, RT is not largely used, mainly because of some technical difficulties but new RT technologies may be proposed to treat large skin surfaces.

Conclusions

New treatment programs offer good results, with median survival of more than 12 years in early-stage MF, but the median survival of 2.5 years or less in advanced stages is still a challenge. RT remains an option for all stages with a good cost/effectiveness ratio in a curative or palliative setting. New RT technologies can overcome some technical problems of treating large skin surfaces.     

The role of para-aortic nodal irradiation in cervical cancer

The current standard of care for locally advanced cervical cancer is whole pelvis and para-aortic radiation when indicated, delivered concomitantly with chemotherapy and brachytherapy. Para-aortic node involvement is a predictor of survival in locally advanced disease but presence of metastases is difficult to determine because the currently available imaging methods lack enough sensitivity to be able to detect accurately para-aortic metastases when surgical staging is not feasible. The objective of this review is to describe the current status of para-aortic lymph node irradiation in locally advanced cervical cancer. It includes analysis of the diagnostic imaging and surgical approaches for assessment of para-aortic lymph node dissemination, together with indications for radiotherapy and radiotherapeutic techniques.     

The role of radiotherapy in the prevention of recurrence and central nervous system metastases in childhood medulloblastoma

PURPOSE: To present the postoperative radiotherapy technique in children with medulloblastoma, and analyse the effectiveness of radiotherapy and the survival data. MATERIALS AND METHODS: 66 consecutive children (45 male and 21 female) received postoperative chemotherapy and radiotherapy between 1986 and 1998. The mean age was 8.3 years. The radiotherapy was performed with linear accelerator 9MV X-ray irradiation. The high risk patients received 36 Gy craniospinal irradiation, the low risk patients recived 30 Gy. The boost irradiation to the posterior fossa was 20 Gy in both patient groups. The patients received multi-drug chemotherapy immediately after the tumor resection. The radiotherapy started 6-8 weeks after the operation. RESULTS: All 66 patients were evaluated. The mean follow-up time was 45.4 months. The chance of cure is higher at age 8 or more, and less favorable under age 8. After 60 months 68.6% of children under age 8 and 75.9% older than 8 are alive. 20 children (64.5%) are alive after radical tumorectomy and 11 died. The 5 year overall survival was 71%. Recurrence was observed in 23/66 cases, it was the most frequent cause of death. Local failure was in posterior fossa in 15 patients (68.2%). CONCLUSION: The radicality of operation had no significant influence to the overall survival. The tumor stage, age of patients, risk group and metastases are important prognostic factors.     

The future of Radiation Oncology: Considerations of Young Medical Doctor

Radiation therapy plays an increasingly important role in the management of cancer. Currently, more than 50% of all cancer patients can expect to receive radiotherapy during the course of their disease, either in a primary management (radical or adjuvant radiotherapy) or for symptom control (palliative radiotherapy).Radiation oncology is a very unique branch of medicine connected with clinical knowledge and also with medical physics. In recent years, this approach has become increasingly absorbed with technological advances. This increasing emphasis on technology, together with other important changes in the health-care economic environment, now place the specialty of radiation oncology in a precarious position. New treatment technologies are evolving at a rate unprecedented in radiation therapy, paralleled by improvements in computer hardware and software. These techniques allow assessment of changes in the tumour volume and its location during the course of therapy (interfraction motion) so that re-planning can adjust for such changes in an adaptive radiotherapy process.If radiation oncologists become simply the guardians of a single therapeutic modality they may find that time marches by and, while the techniques will live on, the specialty may not. This article discusses these threats to the field and examines strategies by which we may evolve, diversify, and thrive.     

Hormonal therapy combined with radiotherapy in locally advanced prostate cancer

At present radiation therapy and radical prostatectomy are considered to be the treatment of choice for clinical T1-T2 prostate cancer. In a more advanced stage of the disease (T3) 10-year overall survival is observed in approximately 40% of patients treated with conventional radiotherapy. So far only a few methods for improving the efficacy of radiotherapy have been introduced. One of them is a three-dimensional conformal radiotherapy with 3 dimensional treatment planning. These novel methods make it possible to escalate the dose to the target and protect healthy tissue at the same time. The optimal volume of irradiation, total dose, fraction dose, techniques of radiotherapy, and the end points used during the follow-up are open to debate. In recent years a few clinical trials involving hormonal therapy and radiotherapy have been carried out. The most important of these are: RTOG 8307, RTOG 8610, RTOG 9202, and EORTC 22863.In the RTOG 8307 trial the comparison of outcomes of a combined treatment with a matched-control group of patients treated by radiotherapy alone has shown that adding hormonal therapy to radiotherapy resulted in a better outcome. Another trials RTOG 8531 and RTOG 8610 produced benefit due to the implementation of hormonal therapy in radiotherapy. The EORTC trial No. 22863 showed improvement in the 5-year overall survival when hormonal therapy after the completion of radiotherapy was continued for 3 years in the investigational arm. The RTOG 9202 study indicated benefit obtained from 2 years of adjuvant hormonal therapy.The results of these trials have had a substantial impact on the management of locally advanced prostate cancer, but there are still questions that have to be answered. There is no doubt that hormonal therapy is an important component of the management of locally advanced prostate cancer. Still the optimal combination of drugs and the timing of such treatment remains controversial. Considering the potential side effects of a combined treatment on the quality of life of patients and care costs, additional properly designed randomised trials are needed to identify the subgroup of patients who will obtain the greatest benefit. Currently, it can be concluded that in the group of patients with a high risk of relapse by adding hormonal therapy to radiotherapy the outcome of treatment in patients with prostate cancer has improved.     

A role for tumor markers in therapeutic decisions after chemotherapy induction of objective remission in stage III epithelial ovarian neoplasms

The management of advanced stage ovarian carcinomas is presently based on initial surgical debulking, multiple drug chemotherapy including cisplatinum, second-look laparotomy. Such an aggressive approach has improved objective response rates and expected survival time, but no dramatic change has been demonstrated as for definitive cure percentages. Many Authors have attempted to turn an optimal objective response to chemotherapy (no residual or minimal residual disease at second-look) into a definitive cure with irradiation. Some reports show satisfactory results, but a high incidence of bowel obstructive complications has been demonstrated, probably due to multiple surgical manipulations before radiotherapy. A reliable diagnostic tool, that could help to avoid the second-look laparotomy (whose inherent role in improving survival is not assessed) should be therefore useful. The possible role of serum tumor markers determinations, for this purpose, is here discussed on the ground of a series of 20 patients affected by stage III ovarian carcinoma. Following this experience, a valuable role seems attributable to CA 125 in monitoring tumor response. Patients achieving values under 35 U/ml before second-look laparotomy showed tumor residuals in the range O-microscopic- less than 1 cm., that is, neoplastic localizations reliable for consolidation radiation therapy.     

Dependence of the nucleoside effect on linear energy transfer.

L929 cells were irradiated by cyclotron-produced neutrons and by 14.8 MeV monoenergetic neutrons. For comparison cells were also irradiated by 60Co gamma rays. Following irradiation cells were treated by an equimolar solution of deoxyribonucleosides, and the effect on cell survival measured. Results show that nucleoside treatment was efficient after low-LET irradiation: gamma ray survival curves were altered by deoxyribonucleosides in terms of significantly increased extrapolation numbers only, but without Do change. Cells irradiated by neutrons from either of the two sources did not respond to nucleoside treatment, and consequently their survival curves remained unaltered. These results show that the nucleoside effect does occur after low-LET irradiation, but apparently not following high-LET irradiation. Since deoxyribonucleosides as well as other cell breakdown products are released in irradiated and necrotic tumours due to massive cell destruction, such a nucleoside effect could possibly enhance the cell survival and thus effect the result of radiotherapy. Absence of the nucleoside effect in case of high-LET irradiation may therefore be an additional potential gain from neutrons in radiotherapy.