Lymphedema: separating fact from fiction

Lymphedema is a feared complication of cancer treatment and one that negatively impacts survivorship. The incidence of breast cancer-related lymphedema ranges from 6% to 70%, but lymphedema may be a common and under-reported morbidity. No standard guidelines for its diagnosis and assessment exist. Although the true etiology of lymphedema remains unknown, radiation, chemotherapy, type of breast surgery, and extent of axillary surgery are commonly cited risk factors. However, the relationship between the number of nodes removed and the risk of lymphedema is not clearly correlated. Clinical trials are focusing on ways to reduce the need for axillary dissection even in the setting of a positive sentinel node, to help minimize axillary morbidity. Risk-reduction practices, including avoidance of skin puncture and blood pressures in the ipsilateral upper extremity, and precautionary behaviors such as wearing compression garments during air travel continue to be advocated by the medical and survivor communities, despite a lack of rigorous evidence supporting their benefit. Emerging data support exercise in at-risk and affected women with lymphedema when started gradually and increased cautiously.     

Idiopathic midline destructive disease: fact or fiction

The differential diagnosis of a progressive destructive lesion of the midface and upper airway region includes both neoplastic and non-neoplastic entities; of these, the majority of cases prove to be either Wegener's granulomatosis or lymphoma. Historically, these sorts of necrotizing midfacial lesions were diagnosed clinically, and as a consequence a variety of overlapping categories of disease sprang up. As pathologic examination of biopsy material became both more widespread and (particularly in the last several years) more sophisticated, many lesions previously thought to be of mysterious origins have proven to be examples of lymphoma (in particular, sinonasal natural killer cell or T cell [NK/T] lymphomas). At present, the evaluation of a patient with a progressive destructive process involving the midface region should include imaging studies (to delineate the extent of disease) as well as biopsy (with sampling of lesional tissue for application of sophisticated testing--including immunohistochemical studies, flow cytometry, or molecular studies as necessary--to exclude the possibility of a NK/T cell lymphoma). There remain occasional patients whose necrotizing midfacial lesions continue to be difficult to classify despite the application of extensive testing; such patients are sometimes described as suffering from the nebulous entity of "idiopathic midline destructive disease". While it remains to be seen whether such patients will ultimately be assigned to other diagnostic groups (as, for example, occult toxic injuries--as in the case of cocaine abusers who are not forthcoming with regard to their drug usage), it seems likely that "idiopathic midline destructive disease" is a diagnostic term of questionable validity which should be used only with extreme reticence in modern practice.     

The rise of fluoroquinolone resistance: fact or fiction

Fluoroquinolone antibiotics have been available since the 1980s when ciprofloxacin and norfloxacin were licensed. Structural revisions of the quinolone molecule have provided new compounds that were well suited to the treatment of upper and lower community-acquired respiratory tract infections, having good activity against Streptococcus pneumoniae. Nevertheless, it was only a matter of time before the pneumococcus developed effective resistance against these new agents. There are populations of fluoroquinolone-resistant S. pneumoniae and, more worryingly, many of these strains are also resistant to penicillin and to macrolides. Surveillance studies such as PROTEKT (Prospective, Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) can provide an early warning system and, with the provision of global surveillance on a local level, can assist in the selection of empirical antibiotic treatment. The new ketolide antibiotic, telithromycin, has excellent activity against the major community-acquired respiratory pathogens (including atypical/intracellular organisms), and has the advantage of retaining its activity against strains of S. pneumoniae that are resistant to penicillin, macrolides and fluoroquinolones.     

Radiotherapy during pregnancy for clinical stages IA-IIA Hodgkin's disease.

Between 1956 and 1990, 775 women were treated for Hodgkin's disease at The University of Texas M.D. Anderson Cancer Center. Of these, 25 (3.2%) were pregnant at diagnosis. Seven of these women were in the first trimester, 10 in the second, and eight in the third. Prior to treatment, three women in the third trimester had normal deliveries, and six patients in the first trimester had abortions. Sixteen patients received radiotherapy for supradiaphragmatic presentations during their pregnancies. All these patients had nodular sclerosing Hodgkin's disease: Two had clinical stage IA presentations and 14 had clinical stage IIA. In two patients radiotherapy (35 Gy) was limited to the neck, three patients were treated definitively to the neck and mediastinum (40 Gy), and 11 patients received mantle irradiation (40 Gy). Four to five half-value layers of lead were used to shield the uterus during radiotherapy. The dose to the fetus was estimated individually in nine patients, using a combination of an Alderson-Rando and a water phantom. The estimated total dose to the mid-fetus ranged from 1.4 to 5.5 cGy for treatment with 6 MV photons, and from 10 to 13.6 cGy for Cobalt 60. All 16 patients subsequently delivered full-term, normal infants. Following delivery, all of the patients had further staging procedures; eight received additional treatment. Subsequently, the disease relapsed in four patients; two eventually died of Hodgkin's disease. The 10-year determinant and overall survival rates were 83% and 71%, respectively. Currently, all offspring are physically and mentally normal, and none has developed a malignancy. Radiotherapy is an appropriate initial treatment for supradiaphragmatic presentations of Hodgkin's disease during the second and third trimesters of pregnancy, provided special attention is paid to treatment and shielding techniques. The outcome for women treated with irradiation for clinical stage I and II Hodgkin's disease during pregnancy has not been shown to be adversely affected by pregnancy, and after the first 8 weeks of gestation, the risk to the fetus appears to be minimal.     

Radiotherapy for glioma during pregnancy: fetal dose estimates, risk assessment and clinical management

Cancer in pregnancy is relatively uncommon, but constitutes a major problem. We report the measurement of scatter dose to the fetus and the estimated fetal risk from that exposure in an illustrative case of a patient, 20 weeks pregnant, with a grade 3 anaplastic astrocytoma. A clinical decision was made to withhold radiotherapy, if possible, until after delivery. Sequential magnetic resonance imaging (MRI) showed no progression during the pregnancy. In the event, she was managed conservatively until the successful completion of her pregnancy. In case radiotherapy was required, an estimation of the fetal risk was made. Phantom measurements were undertaken to assess the likely fetal dose. Film badges were used to estimate the scattered radiation energy. Measurements were made on a Varian 600C at 6 MV and Asea Brown Boveri (ABB) accelerator at 8 and 16 MV. Doses were measured at 30, 45 and 60 cm from the isocentre; the fetus was assumed to lie at about 60 cm and not closer than 45 cm from the isocentre. Estimated doses to the position of the fetus were lowest with the 6 MV Varian accelerator. Using this machine without additional abdominal shielding, the estimated dose on the surface at 45 cm from the tumour volume was 2.2 cGy for a tumour dose of 54 Gy; using the ABB accelerator, the dose varied between 49-59 cGy. The energy of scattered radiation was in the range 208-688 keV, so that additional shielding would be practical to further reduce the fetal dose. The risk of cancer up to the age of 15 years attributable to radiation is 1 in 1700 per cGy, of which half will be fatal (i.e. 1 in 3300 per cGy). A dose of 2.2 cGy adds a risk of fatal cancer by the age 15 years of only 1 in 1500. Because the addition of shielding might halve the fetal dose, this risk should be reduced to 1 in 3000. For comparison, the overall UK risk of cancer up to the age 15 years is 1 in 650. In conclusion, careful choice of linear accelerator for the treatment of a pregnant woman and the use of additional shielding is valuable, as this can dramatically affect fetal dose.     

Radiotherapy for Hodgkin's disease in pregnancy

Hodgkin's disease diagnosed during pregnancy poses a dilemma as there are risks of abortion and fetal malformation with the use of radiotherapy and chemotherapy. A patient with Hodgkin's disease during pregnancy treated with radiotherapy is presented.     

Radiotherapy for metastatic melanoma presenting in pregnancy

We describe the study of a patient with metastatic melanoma to axillary nodes presenting during pregnancy. The factors considered in her management are discussed, including issues related to staging, the decision not to terminate the pregnancy and the relative efficacy and fetal toxicity of the available treatment options. An overview of the known effects of radiotherapy on the fetus is presented and the technical alterations that were used to decrease the toxicity of radiotherapy are discussed.     

Radiotherapy of Hodgkin's disease in early pregnancy: embryo dose measurements.

BACKGROUND AND PURPOSE: Limited information exists on the possibility of pregnant women undergoing radiotherapy for Hodgkin's disease in early pregnancy. The purpose of this study was to measure embryo dose resulting from treatment of supra-diaphragmatic Hodgkin's disease at the first trimester of gestation. MATERIALS AND METHODS: A humanoid phantom was used to simulate pregnancy at the first trimester of gestation. Embryo dose, was measured using three different field sizes that may be applied for local field irradiation in each of the regions of neck, axilla, neck-mediastinum and for mantle treatment. A shielding device consisting of 5 cm of lead was used to reduce the embryo dose. Dose measurements were carried out using thermoluminescent dosimeters. Phantom exposures were made with a 6 MV photon beam. RESULTS: Local field irradiation in the regions of neck or axilla always resulted in embryo doses below 10 cGy. For local field irradiation in the region of neck-mediastinum and for mantle treatment, the radiation dose to a shielded embryo was 2.8-18.6 and 4.2-24.5 cGy depending upon the distance from the field isocenter and the field size used, respectively. The corresponding dose for an unshielded embryo exceeded 10 cGy. All the above embryo doses were obtained for a tumor dose of 40 Gy. CONCLUSIONS: Local field irradiation in the regions of neck or axilla may be safely performed even without uterus shielding. For local field irradiation in the region of neck-mediastinum and for mantle radiotherapy, the extent of the irradiated area, the distance separating the embryo from the field isocenter and the tumor dose are the factors, determining whether the radiation dose to a shielded embryo may possibly be reduced below 10 cGy.     

Breast cancer during pregnancy: A mini-review

Background

As modern women delay childbearing, pregnancy-associated breast cancer (PABC) becomes a more frequent problem faced by oncologists, gynecologists, and obstetricians alike. However, no evidence exists concerning the management of this condition.

Methods

We summarized the current literature regarding epidemiology, pathology, diagnosis, treatment and prognosis of PABC. Data were collected by searching PubMed and Medline for the period from 1950 to 2007.

Results

There are no randomized controlled trials regarding PABC management. Current evidence suggests that diagnosis may be carried out with limitations regarding staging; surgical treatment may be performed as for the non-pregnant women. Radiotherapy and endocrine therapy are contraindicated during pregnancy, while chemotherapy is allowed after the first trimester. Prognosis is considered poor. Subsequent pregnancy is allowed only 2 years after completing treatment.

Conclusions

Due to lack of prospective randomized controlled clinical studies, both ongoing studies and future evidence are expected to solve problems related to breast cancer management during pregnancy.